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Balancing biocompatibility and drug-loading efficiency in nanoparticles presents a significant challenge. In this study, we describe the facile fabrication of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine (PAA-mZnP/PDA) Janus nanoparticles (JNPs). The PDA half-shell itself can serve as a photothermal agent for photothermal therapy (PTT), as well as to offers sites for polyethylene glycol (PEG) to enhance biocompatibility. Concurrently, the mesoporous ZnP core allows high loading of doxorubicin (DOX) for chemotherapy and the Cy5.5 dye for fluorescence imaging. The resultant PAA-mZnP/PDA-PEG JNPs exhibit exceptional biocompatibility, efficient drug loading (0.5 mg DOX/1 mg JNPs), and dual pH/NIR-responsive drug release properties. We demonstrate the JNPs' satisfactory anti-cancer efficacy, highlighting the synergistic effects of chemotherapy and PTT. Furthermore, the potential for synergistic fluorescence imaging-guided chemo-phototherapy in cancer treatment is illustrated. Thus, this work exemplifies the development of biosafe, multifunctional JNPs for advanced applications in cancer theranostics. Facile fabrication of monodispersed nanomedicine with multi-cancer killing modalities organically integrated is nontrivial and becomes more challenging under the biocompatibility requirement that is necessary for the practical applications of nanomedicines. In this study, we creatively designed PAA-mZnP/PDA JNPs and fabricated them under mild conditions. Our method reliably yields uniform JNPs with excellent monodispersity. To maximize functionalities, we achieve fourfold advantages including efficient drug/fluorescent dye loading, PTT, pH/NIR dual-responsive properties, and optimal biocompatibility. The as-fabricated JNPs exhibit satisfactory anti-cancer performance both in vitro and in vivo , and demonstrate the potential of JNPs in fluorescence imaging-guided synergistic cancer chemo-phototherapy. Overall, our research establishes a pathway in versatile inorganic/polymer JNPs for enhanced cancer diagnosis and therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Dou Zhang,1,2,* Xuyi Liu,1,2,* Xiong Li,3,* Xinyi Cai,1,2 Zhenying Diao,1,2 Long Qiu,1,2 Xuelin Chen,1,2 Yuyu Liu,1,2 Jianbo Sun,1 Daxiang Cui,1,4 Qiaoyuan Ye,5 Ting Yin1,2 1Research Center of Nano Technology and Application Engineering, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 2Dongguan Biomedical Nano Engineering Technology Research Center, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 3Department of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 4School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 5Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoyuan Ye, Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email 13650248189@163.com Ting Yin, Research Center of Nano Technology and Application Engineering, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email wsyt132@163.comPurpose: Melanoma is a highly aggressive and dangerous malignant skin tumor and there is an urgent need to develop effective therapeutic approaches against melanoma. The main objective of this study was to construct a multifunctional nanomedicine (GNR@PEG-Qu) to investigate its therapeutic effect on melanoma from the oxidative stress pathway.Methods: First, the nanomedicine GNR@PEG-Qu was synthesized and characterized, and its photothermal and antioxidant properties were confirmed. In addition, in vivo imaging capabilities were observed. Finally, the tumor inhibitory effects of GNR@PEG-Qu in vivo and in vitro as well as its biosafety were observed.Results: GNR@PEG-Qu shows good photothermal and anti-oxidation properties. Following exposure to 1064 nm laser irradiation in the second near-infrared II (NIR-II) window, GNR@PEG-Qu shows anti-tumor ability through low-temperature photothermal therapy (PTT) adjuvant drug chemotherapy. GNR@PEG-Qu makes full use of the antioxidant capacity of quercetin, reduces ROS levels in melanoma, alleviates oxidative stress state, and achieves “oxidative stress avoidance” at the tumor site. Quercetin can also downregulate the expression of the heat shock protein Hsp70, which will improve the thermal sensitivity of the tumor site and enhance the efficacy of low-temperature PTT.Conclusion: GNR@PEG-Qu nanoagent exhibits synergistic treatment and high tumor inhibition effects, which is a promising strategy developed to achieve oxidative stress avoidance and synergistic therapy of melanoma using quercetin (Qu)-coated gold nanorod (GNR@PEG).Keywords: melanoma, gold nanorods, quercetin, chemo-photothermal therapy, oxidative stress

Fang Fang,1,* Yun Yan Chen,1,* Xin-Ming Zhang,2 Jin Tang,1 Yu-Hao Liu,1 Chen-Shuo Peng,1 Yu Sun1,3 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2School of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241002, People’s Republic of China; 3Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932026, Email whsunyu@163.comBackground: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy. Keywords: Chemo-photothermal therapy, Targeted cancer therapy, Nanoparticles, Cetuximab, Indocyanine green

Hepatocellular carcinoma is a serious illness with a high rate of mortality. A high dose of theranostic drugs with efficient diagnostic and therapeutic capabilities should be required. Chemo-photothermal therapy is presently recognized as a secure method of cancer treatment that specifically targets tumour tissue or cells. Additionally, the success of cancer therapy is increased by the use of targeted nanoparticles. The current study aims to investigate the interaction between phototherapy and the anti-hepatocellular carcinoma treatment combination HA-GEM-MoS2/ZnO nanocomposites (NCs) loaded with gemcitabine and molybdenum disulphide. NCs were synthesized and characterized using FT-IR, XRD, TEM, and DLS analyses. The present investigation shows that the synthesized HA-MoS2/ZnO nanocomposites were elongated spherical in shape and their sizes ranged from 62.3 to 75.7 nm according to the estimation using XRD results, which is consistent with TEM findings. Further, HA-MoS2/ZnO nanocomposites could effectively encapsulate the GEM, showing dual pH and thermal triggered drug release behaviour. The result of cell uptake tests clearly demonstrated improved cellular uptake of synthesized nanocomposites following HA and GEM-loaded NCs in hepatocellular carcinoma cell lines. In addition, combination therapies caused the highest incidence of cell death in hepatocellular carcinoma, according to cytotoxicity experiments and showed a good compatibility. In vitro studies prove that HA-GEM-MoS2/ZnO nanocomposites enhanced tumour treatment that combines chemotherapy and photothermal therapy to remove the tumour and prevent relapses. Still, no studies have been done to see if gemcitabine-encapsulated HA-MoS2/ZnO NCs inhibit human hepatocellular carcinoma cell. Hence, the current study can give a new paradigm for the diagnosis and treatment of cancer and the outcome may be helpful to improve the quality of cancer patient's life. [ABSTRACT FROM AUTHOR]

The strategic integration of multi-functionalities within a singular nanoplatform has received growing attention for enhancing treatment efficacy, particularly in chemo-photothermal therapy. This study introduces a comprehensive concept of Janus nanoparticles (JNPs) composed of Au and Fe 3 O 4 nanostructures intricately bonded with β-cyclodextrins (β-CD) to encapsulate 5-Fluorouracil (5-FU) and Ibuprofen (IBU). This strategic structure is engineered to exploit the synergistic effects of chemo-photothermal therapy, underscored by their exceptional biocompatibility and photothermal conversion efficiency (∼32.88 %). Furthermore, these β-CD-conjugated JNPs enhance photodynamic therapy by generating singlet oxygen (1O 2) species, offering a multi-modality approach to cancer eradication. Computer simulation results were in good agreement with in vitro and in vivo assays. Through these studies, we were able to prove the improved tumor ablation ability of the drug-loaded β-CD-conjugated JNPs, without inducing adverse effects in tumor-bearing nude mice. The findings underscore a formidable tumor ablation potency of β-CD-conjugated Au-Fe 3 O 4 JNPs, heralding a new era in achieving nuanced, highly effective, and side-effect-free cancer treatment modalities. The emergence of multifunctional nanoparticles marks a pivotal stride in cancer therapy research. This investigation unveils Janus nanoparticles (JNPs) amalgamating gold (Au), iron oxide (Fe 3 O 4), and β-cyclodextrins (β-CD), encapsulating 5-Fluorouracil (5-FU) and Ibuprofen (IBU) for synergistic chemo-photothermal therapy. Demonstrating both biocompatibility and potent photothermal properties (∼32.88 %), these JNPs present a promising avenue for cancer treatment. Noteworthy is their heightened photodynamic efficiency and remarkable tumor ablation capabilities observed in vitro and in vivo , devoid of adverse effects. Furthermore, computational simulations validate their interactions with cancer cells, bolstering their utility as an emerging therapeutic modality. This endeavor pioneers a secure and efficacious strategy for cancer therapy, underscoring the significance of β-CD-conjugated Au-Fe 3 O 4 JNPs as innovative nanoplatforms with profound implications for the advancement of cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

In anti‐cancer metastasis treatment, precise drug delivery to cancer cells remains a challenge. Innovative nanocomposites are developed to tackle these issues effectively. The approach involves the creation of manganese oxide (Mn3O4) nanoparticles (NPs) and their functionalization using trisodium citrate to yield functionalized Mn3O4 NPs (F‐Mn3O4 NPs), with enhanced water solubility, stability, and biocompatibility. Subsequently, the chemotherapeutic drug doxorubicin (DOX) is encapsulated with Mn3O4 NPs, resulting in DOX/Mn3O4 NPs. To achieve cell‐specific targeting, These NPs are coated with HeLa cell membranes (HCM), forming HCM/DOX/Mn3O4. For further refinement, a transferrin (Tf) receptor is integrated with cracked HCM to create Tf‐HCM/DOX/Mn3O4 nanocomposites (NC) with specific cell membrane targeting capabilities. The resulting Tf‐HCM/DOX/Mn3O4 NC exhibits excellent drug encapsulation efficiency (97.5%) and displays triggered drug release when exposed to NIR laser irradiation in the tumor's environment (pH 5.0 and 6.5). Furthermore, these nanocomposites show resistance to macrophage uptake and demonstrate homotypic cancer cell targeting specificity, even in the presence of other tumor cells. In vitro toxicity tests show that Tf‐HCM/DOX/Mn3O4 NC achieves significant anticancer activity against HeLa and BT20 cancer cells, with percentages of 76.46% and 71.36%, respectively. These results indicate the potential of Tf‐HCM/DOX/Mn3O4 NC as an effective nanoplatform for chemo‐photothermal therapy. [ABSTRACT FROM AUTHOR]

Abstract Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer. Graphical Abstract

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer. [ABSTRACT FROM AUTHOR]

The development of a theranostic platform that integrates multiple modalities into a single entity is a hopeful approach for effective cancer treatment but still a challenge. This study presents a smart and versatile theranostic nanoplatform for remarkably potent in vivo synergistic chemo-photothermal tumor treatment, guided by MR/fluorescence dual-mode imaging utilizing a pH-responsive strategy. We encapsulated Gd3+-based carbon quantum dots (GCDs) and doxorubicin (DOX) within hollow mesoporous Prussian blue nanoparticles (HMPB NPs). This innovative theranostic platform, named DOX/GCDs-HMPB NPs, facilitates targeted drug release and simultaneous MR/fluorescence imaging, specifically at the tumor site. At physiological pH, both GCDs and DOX molecules are encapsulated within the mesoporous hollow network of the nanoparticles, with the metal–ligand coordination bonding between Gd species and DOX molecules, to restrict water molecules' access to the Gd3+ center, thus minimizing proton relaxivity. In the acidic tumor microenvironment, GCDs and DOX drug molecules are released simultaneously from the nanoparticles and enhance both MR contrast and fluorescence, leading to an increase in chemotherapeutic activities. This system reveals strong pH-switching theranostic performance for 4T1 cells, with high-efficiency chemotherapy and considerable photothermal conversion, indicating practical application for synergistic chemo-photothermal treatment of tumors. A promising strategy for developing a theranostic platform for cancer treatment and diagnosis is introduced. [ABSTRACT FROM AUTHOR]

Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] The reactive oxygen species (ROS) produced through the Fenton reaction, induces lipid peroxide (LPO), causing cellular structural damage and ultimately triggering ferroptosis. However, the generation of ROS in the tumor microenvironment (TME) is limited by the catalytic efficiency of the Fenton reaction. Herein, a novel hollow mesoporous silica nanoparticle (HMSN) combined with multi-metal sulfide-doped mesoporous silica nanocatalyzers (NCs) was developed, namely M x S y -HMSN NCs (M represents Cu Mn and Fe, S denotes sulfur). The M x S y -HMSN can dramatically enhanced the ferroptosis by: (1) facilitating the conversion of H 2 O 2 to ·OH through Fenton or Fenton-like reactions through co-catalysis; (2) weakening ROS scavenging systems by depleting the over expressed glutathione (GSH) in TME; (3) providing exceptional photothermal therapy to augment ferroptosis. The M x S y -HMSN can also act as smart cargos for anticancer drug-doxorubicin (DOX). The release of DOX is responsive to GSH/pH/Near-infrared Light (NIR) irradiation at the tumor lesion, significantly improving therapeutic outcomes while minimizing side effects. Additionally, the M x S y -HMSN has demonstrated excellent magnetic resonance imaging (MRI) potential. This smart M x S y -HMSN offer a synergetic approach combining ferroptosis with chemo-photothermal therapy and magnetic resonance imaging (MRI) diagnose, which could be an informative guideline for the design of future NCs. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials. [ABSTRACT FROM AUTHOR]

Abstract Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol–gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte–tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis. [ABSTRACT FROM AUTHOR]

Abstract Background The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). Results In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. Conclusion This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

Abstract Background Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC. Methods Inspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis. Results This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. Conclusions Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance. Graphical Abstract

Yipengchen Yin,1,* Jiaxin Sun,2,* Tiaoyan Jiang,1 Li Zhu,3 Wenchao Gu,4 Sheng Wang,5 Le Song,6 Changchun Wang,2 Qin Zhang1 1Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China; 2State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai, 200438, People’s Republic of China; 3Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China; 4Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki, 305-8575, Japan; 5Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 6Department of Gerontology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Zhang; Le Song, Email zhangqin@shsmu.edu.cn; song.le@zs-hospital.sh.cnIntroduction: Sentinel lymph node (SLN) is the first regional lymph node where tumor cells metastasize, and its identification and treatment are of great significance for the prevention of tumor metastasis. However, the current clinical modalities for identification and treatment of SLN are still far from satisfactory owing to their high cost, invasiveness and low accuracy. We aim to design a novel nanomedicine system for SLN imaging and treatment with high efficacy.Methods: We designed and prepared hollow mesoporous carbon spheres (HMCS) and loaded with the chemotherapeutic drug doxorubicin (DOX), which is then modified with polyvinyl pyrrolidone (PVP) to obtain nanomedicine: HMCS-PVP-DOX.Results: HMCS-PVP with a size of about 150 nm could retain in the lymph nodes for a long time and stain the lymph nodes, which could be easily observed by the naked eye. At the same time, HMCS-PVP exhibited excellent photoacoustic and photothermal imaging capabilities, realizing multimodal imaging to locate lymph nodes precisely. Due to its high specific surface area, HMCS could be largely loaded with the chemotherapeutic drug doxorubicin (DOX). HMCS-PVP-DOX displayed highly efficient synergistic chemotherapy-photothermal therapy for lymphatic metastases in both cellular and animal experiments due to its significant photothermal effect under 1064 nm laser irradiation. HMCS-PVP-DOX also displayed great stability and biosafety.Discussion: Multifunctional nanomedicine HMCS-PVP-DOX is expected to provide a novel paradigm for designing nanomedicine to the diagnosis and treatment of lymphatic metastases because of its good stability and safety.Graphical Abstract: Keywords: tumor lymphatic metastasis theranostics, hollow mesoporous carbon nanospheres, sentinel lymph node, tri-modal imaging, chemo-photothermal therapy

Hui Zhu,1,2 Ke Yang,3 Huan Yao,1 Xueying Chen,1 Shujin Yan,1,2 Yiman He,1,2 Yang Cao,2 Jie Luo,1 Dong Wang1 1Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People’s Republic of China; 3Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jie Luo; Dong Wang, Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email luojie1983@cqmu.edu.cn; wangdong4429@cqmu.edu.cnBackground: Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis.Methods: Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated.Results: IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of − 6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on-site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors.Conclusion: Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically.Keywords: immunogenic cell death, immunotherapy, checkpoint blockade, chemo-photothermal therapy, triple-negative breast cancer

Background: The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). Results: In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. Conclusion: This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC. [ABSTRACT FROM AUTHOR]

Combined chemo-photothermal therapy (CT-PTT) based on gold nanorods (AuNRs) loaded with chemotherapies has been recently introduced as a promising anticancer therapy with relatively lower side effects and higher efficacy over individual therapeutic approaches. We fabricated β-cyclodextrin-based nanosponges encapsulating PEGylated gold nanorods and doxorubicin (DOX), AuNR-S-PEG.β-CD NS-DOX, comprehensively characterized it using TEM, SEM, FE-SEM, FITR, and DLS and then evaluated it for CT-PTT versus the respective photothermal, AuNR-S-PEG.β-CD NS, and chemotherapy DOX. The synthesized AuNR-S-PEG.β-CD NS nanocomposite exhibited high photothermal conversion efficiency and high drug loading capacity based on the porous structure of the nanosponges. The drug-loaded nanocomposites, AuNR-S-PEG.β-CD NS-DOX, showed pH/NIR dual-responsive drug release behaviors, good biocompatibility, and efficient uptake into A549 lung cancer cells, as well as higher efficiency in killing cancer cells than single chemo- or photothermal therapy. Overall, the findings of this study demonstrate AuNR-S-PEG.β-CD NS-DOX nanocomposites as a promising candidate for combined chemo-photothermal therapy of lung cancer. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is typically the first-line treatment for the advanced stage of cancers. However, there are shortcomings with respect to conventional chemotherapy that limit therapeutic efficiency, including lack of tumor selectivity, systemic toxicity and drug resistance. Objective: A multifunctional nanoplatform was build using of hydrogel co-loaded containing cisplatin and Iron oxide–gold core-shell nanoparticles. The Au shell comprises the light response and the iron core can be utilized as a negative contrast agent in nanocomplex.Material and Methods: In this experimental study, KB cells derived from the epithelial cells located in the nasopharynx were exposed to different levels of concentration of hydrogel co-loaded with cisplatin and Iron oxide–gold core-shell nanoparticles. Afterwards, the cytotoxicity was determined using MTT assay. Results: The cytotoxicity results showed that this nanoplatforms has potent to create higher cytotoxicity in KB cells than free cisplatin, so that Fe-Au@Alg and Fe-Au@Alg with cisplatin mixed with laser irradiation exhibited a significant reduction in cell viability after 5 min. Conclusion: Hydrogel co-loaded with cisplatin and Iron oxide–gold core–shell nanoparticles are stable construct to combine chemo-photothermal therapy. Therefore, they can be used as a computed tomography-traceable nanocarrie, enabling us to monitor the delivery of therapeutics.

Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm2) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.

Green synthesis strategies have been widely applied for the preparation of versatile nanomaterials. Gold nanospheres with an average size of 6.95 ± 2.25 nm were green synthesized by using a 70% ethanol extract of Korean red ginseng (Panax ginseng Meyer) root as a reducing agent. A seed-mediated synthesis was conducted to prepare Au–Ag bimetallic nanoparticles using gold nanospheres as seeds. Remarkably, Au–Ag bimetallic nanoparticles with an average size of 80.4 ± 11.9 nm were synthesized. Scanning transmission electron microscopy, energy dispersive X-ray spectroscopy and elemental mappings revealed bimetallic nanoparticles with Au–Ag alloy core and Au-rich shells. A face-centered cubic structure of Au–Ag bimetallic nanoparticles was confirmed by X-ray diffraction analysis. For Au–Ag bimetallic nanoparticles, the ratio of Ag/Au was 0.20 which was detected and analyzed by inductively coupled plasma-mass spectrometry. Gold nanospheres and Au–Ag bimetallic nanoparticles were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Finally, docetaxel was loaded for evaluating the in vitro cell viability on cancer cells. Successful functionalization was confirmed by Fourier-transform infrared spectra. The anticancer activity of the docetaxel-loaded nanoparticles was higher than that of their non-docetaxel-loaded counterparts. The highest anticancer activity on human gastric adenocarcinoma cells (AGS) was observed in the docetaxel-loaded gold nanospheres that were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Additionally, grafting onto graphene oxide and docetaxel loading induced high intracellular reactive oxygen species generation. For chemo-photothermal (PTT) anticancer therapy, cell viability was investigated using near-infrared laser irradiation at 808 nm. The highest chemo-PTT anticancer activity on AGS cells was observed in the docetaxel-loaded Au–Ag bimetallic nanoparticles. Therefore, the newly prepared docetaxel-loaded Au–Ag bimetallic nanoparticles in the current report have potential applications in chemo-PTT anticancer therapy. [ABSTRACT FROM AUTHOR]

Background: Combination therapy has attracted tremendous interest for its great potential in treating cancers. Materials & methods: Based on chitosan-coated silver nanotriangles, polyethylene glycol, AS1411 aptamer and doxorubicin, a multifunctional nanocomposite (AS1411-DOX-AgNTs) was constructed and characterized. Then the photothermal properties, ability to target breast cancer cells and anti-breast cancer effect of AS1411-DOX-AgNTs were evaluated. Results: AS1411-DOX-AgNTs were successfully fabricated and showed excellent photothermal conversion efficiency, breast cancer cell and tumor targeting ability. Compared with single treatments, the combination of AS1411-DOX-AgNTs with near-infrared irradiation possessed the strongest anti-breast cancer effect in vitro and in vivo. Conclusion: AS1411-DOX-AgNTs hold great potential in targeted DOX delivery and combined chemo–photothermal therapy for breast cancer. This article focuses on nanomaterials, nanomedicine and photothermal therapy (PTT) to treat breast cancer. Nanomaterials refer to materials with at least one dimension in nanometer size (1–100 nm) or materials composed as basic units in a 3D space. Nanomedicine is the application of nanomaterials in medicine. Nanoparticles can deliver drugs to areas that are difficult for the drugs themselves to reach. PTT is a noninvasive tumor therapy that uses photothermal conversion agents to convert light energy into heat energy to kill tumor cells under the irradiation of external near-infrared (NIR) light. In recent years, combination therapy for cancers has drawn more and more attention. In the current study, we investigated the in vitro and in vivo anticancer effects of silver nanocomposites combined with chemotherapy and PTT. The prepared silver nanocomposites showed excellent physicochemical properties and possessed good anti-breast cancer efficacy combined with PTT and chemotherapy drug in vitro and in vivo. The results of this study demonstrated that these prepared silver nanocomposites had exceptional anti-breast cancer effects in combination with PTT and could be promising drug-loaded photothermal conversion agents. Targeted modified drug-loaded silver nanocomposites exhibit a significant anti-breast cancer effect combined with photothermal therapy. [ABSTRACT FROM AUTHOR]

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co -loaded into pH-sensitive nanoparticles (poly(ethylene gly co l)-poly[(benzyl- l -aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors. [Display omitted] • PEG-PABI enhanced colloidal stability via α-helix structure during self-assembly. • GNC-M enhanced photothermal stability while maintaining heat conversion efficiency. • Dox/GNC-M demonstrated a strong synergistic anticancer effect in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανβ3 y ανβ5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer. [ABSTRACT FROM AUTHOR]

Abstract Background As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect. Methods CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay. Results Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively. Conclusion The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP. Graphical Abstract

The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anticancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy. [ABSTRACT FROM AUTHOR]

In this study, we synthesized hollow mesoporous silica nanoparticles (HMSNs) coated with polydopamine (PDA) and a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-modified hybrid lipid membrane (denoted as HMSNs-PDA@liposome-TPGS) to load doxorubicin (DOX), which achieved the integration of chemotherapy and photothermal therapy (PTT). Dynamic light scattering (DLS), transmission electron microscopy (TEM), N2 adsorption/desorption, Fourier transform infrared spectrometry (FT-IR), and small-angle X-ray scattering (SAXS) were used to show the successful fabrication of the nanocarrier. Simultaneously, in vitro drug release experiments showed the pH/NIR-laser-triggered DOX release profiles, which could enhance the synergistic therapeutic anticancer effect. Hemolysis tests, non-specific protein adsorption tests, and in vivo pharmacokinetics studies exhibited that the HMSNs-PDA@liposome-TPGS had a prolonged blood circulation time and greater hemocompatibility compared with HMSNs-PDA. Cellular uptake experiments demonstrated that HMSNs-PDA@liposome-TPGS had a high cellular uptake efficiency. In vitro and in vivo antitumor efficiency evaluations showed that the HMSNs-PDA@liposome-TPGS + NIR group had a desirable inhibitory activity on tumor growth. In conclusion, HMSNs-PDA@liposome-TPGS successfully achieved the synergistic combination of chemotherapy and photothermal therapy, and is expected to become one of the candidates for the combination of photothermal therapy and chemotherapy antitumor strategies. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is typically the first-line treatment for the advanced stage of cancers. However, there are shortcomings with respect to conventional chemotherapy that limit therapeutic efficiency, including lack of tumor selectivity, systemic toxicity and drug resistance. Objective: A multifunctional nanoplatform was build using of hydrogel co-loaded containing cisplatin and Iron oxide--gold core-shell nanoparticles. The Au shell comprises the light response and the iron core can be utilized as a negative contrast agent in nanocomplex. Material and Methods: In this experimental study, KB cells derived from the epithelial cells located in the nasopharynx were exposed to different levels of concentration of hydrogel co-loaded with cisplatin and Iron oxide--gold core-shell nanoparticles. Afterwards, the cytotoxicity was determined using MTT assay. Results: The cytotoxicity results showed that this nanoplatforms has potent to create higher cytotoxicity in KB cells than free cisplatin, so that Fe-Au@Alg and Fe-Au@ Alg with cisplatin mixed with laser irradiation exhibited a significant reduction in cell viability after 5 min. Conclusion: Hydrogel co-loaded with cisplatin and Iron oxide--gold core--shell nanoparticles are stable construct to combine chemo-photothermal therapy. Therefore, they can be used as a computed tomography-traceable nanocarrie, enabling us to monitor the delivery of therapeutics. [ABSTRACT FROM AUTHOR]

Nanodiamonds with magnetic resonance imaging (MRI) and targeted drug delivery to exert combined effects for biomedical applications have been considered to be an urgent challenge. Herein, a novel bio-nanoarchitectonics (Fe3O4@NDs) with simultaneous imaging and therapeutic capacities was fabricated by covalently conjugating nanodiamonds (NDs) with Fe3O4. Fe3O4@NDs exhibited better biocompatibility and excellent photothermal stability with superb photothermal conversion performance (37.2%). Fe3O4@NDs has high doxorubicin (DOX) loading capacity (193 mg/g) with pH and NIR-responsive release characteristics. Fe3O4@NDs loading DOX showed a combined chemo-photothermal inhibitory effect on the tumor cells. Enhanced T2-weighted MRI contrast toward the tumor, with the assistance of a magnetic field, convinced the Fe3O4@NDs gathered in the tumor more efficiently and could be used for MRI-based cancer diagnosis. Our results revealed an effective strategy to achieve a stimuli-sensitive nanoplatform for multifunctional theranostics by the combined action. [ABSTRACT FROM AUTHOR]

This study reports the CD44 receptor-targeted gold-doxorubicin nanocomposite (TGNC-DOX) for pulsatile chemo-photothermal therapy of triple-negative breast cancer (TNBC). The developed TGNC-DOX was nanometric, having a particle size of 71.34 ± 3.66 nm. The doxorubicin was loaded by electrostatic interaction with high entrapment and loading efficiency (>75%). TGNC-DOX showed potent photothermal response and reversible photothermal stability following irradiation with 808 nm NIR laser irradiation. Further, TGNC-DOX showed laser-responsive and pH-dependent drug release behavior suggesting its suitability for chemo-photothermal therapy, specifically at the tumor microenvironment site. Cellular viability, cellular uptake, ROS generation, and apoptosis assays suggested selective localization of TGNC-DOX in cancer cells that showed a significant cytotoxic effect against MDA-MB-231 breast cancer cells. Moreover, the developed TGNC-DOX showed ferroptosis in MDA-MB-231 cells. The event of TGNC-DOX-mediated thermal ablation is marked by a significant generation of reactive oxygen species (ROS) and apoptosis, as affirmed by flow cytometry. NIR-808 laser-responsive photothermal therapy of cancer cells was found to be more effective than without NIR-808 laser-treated cells, suggesting the fundamental role of photothermal ablation. The outcome concludes developed TGNC-DOX is a novel and potential tool to mediate laser-guided chemo-photothermal ablation treatment of cancer cells. [ABSTRACT FROM AUTHOR]

Abstract Two-dimensional (2D) Titanium nanosheets (Ti NSs) have shown many excellent properties, such as nontoxicity, satisfactory photothermal conversion efficacy, etc. However, the biomedical applications of Ti NSs have not been intensively investigated. Herein, we synthesized a multifunctional Ti NS drug delivery system modified with polydopamine/polyethylene glycol (Ti@PDA-PEG) and applied simultaneously for photothermal therapy and chemotherapy. Doxorubicin (DOX) was utilized as a model drug. Ti@PDA-PEG NS shows an ultrahigh antitumor drug DOX loading (Ti@PDA-PEG-DOX). The prepared Ti@PDA-PEG-DOX NS as robust drug delivery system demonstrates great stability and excellent multi-response drug-release capabilities, including pH-responsive and near-infrared -responsive behavior and obviously high photothermal efficiency. Both in vitro and in vivo experimental results have shown high biosafety and outstanding antitumor effects. Therefore, this work exhibits the enormous potential of a multifunctional platform in the treatment of tumors and may stimulate interest in the exploration of other new 2D nanomaterials for biomedical applications. Graphical Abstract

[Display omitted] Stimuli-responsive nanoplatforms have been popular in controlled drug delivery research because of their ability to differentiate the tumor microenvironment from the normal tissue environment in a spatiotemporally controllable manner. The synergistic therapeutic approach of combining cancer chemotherapy with photothermal tumor ablation has improved the therapeutic efficacy of cancer therapeutics. In this study, a UiO-66 metal organic framework (MOF)-based system loaded with doxorubicin (DOX), surface decorated with the photothermal agents indocyanine green (ICG) and polydopamine (PDA), and conjugated with transferrin (TF) was successfully designed to operate as a responsive system to pH changes, featuring photothermal capabilities and target specificity for the purpose of treating breast cancer. The synthesized nanoplatform benefits from its uniform size, excellent DOX encapsulation efficiency (91.66 %), and efficient pH/NIR-mediated controlled release of the drug. In vitro photothermal studies indicate excellent photothermal stability of the formulation even after 6 on–off cycles of NIR irradiation. The in vitro cytotoxicity assessment using an NIR laser (808 nm) revealed that the DOX-loaded functionalized UiO-66 nanocarriers had outstanding inhibitory effects on 4T1 cells because of synergistic chemo-photo therapies, with no substantial toxicity by the carriers. In addition, cellular uptake evaluations revealed that UiO-DOX-ICG@PDA-TF could specifically target 4T1 cells on the basis of receptor-mediated internalization of transferrin receptors. Additionally, in vivo toxicity studies in Wistar rats indicated no signs of significant toxicity. The UiO-based nanoformulations effectively inhibited and destroyed cancer cells under 808 nm laser irradiation because of their minimal toxicity, strong biocompatibility, and outstanding synergistic chemo/photothermal/photodynamic treatment. [ABSTRACT FROM AUTHOR]

Chemo-photothermal therapy (PTT) is an emerging non-invasive cancer treatment modality. Light-responsive porphysomes (DPP IR Mtx @Lipo NPs) nanosystems ablate breast cancer cells upon oxidative stress and hyperthermia. The unique self-assembled porphysomes were formed spherical shape in the size range of 150 ± 30 nm formed by the co-assembly of porphyrins along with IR 775 and chemotherapeutic drug, Mitoxantrone (Mtx), forming a camouflaged nanosystem (DPP IR Mtx @Lipo NPs, porphysomes). The advent of the prepared porphysomes aids in proper tuning of NIR absorbance improving singlet oxygen species generation among other anticancer drugs. The eminent release of DPP and adjuvant chemo-drug, Mitoxantrone from the self-assembled porphysomes is triggered by IR 775, a NIR photosensitizer upon laser irradiation. These multifunctional DPP IR Mtx @Lipo NPs have an efficient photothermal conversion efficiency of 65.8% as well as bioimaging properties. In-vitro studies in 2D and 3D models showed a significant cell death of 4T1 cells via the apoptotic pathway when irradiated with NIR laser, causing minimal damage to nearby healthy cells. DPP IR Mtx @Lipo NPs exhibited commingled PDT/PTT interdependent via NIR laser exposure, leading to mitochondrial disruption. Interestingly, the transient transfection using p53-GFP in cancer cells followed by DPP IR Mtx @Lipo NPs treatment causes rapid cell death. The activation of p53-dependent apoptosis pathways was vividly expressed, evidenced by the upregulation of Bax and increased pattern of Caspase-3 cleavage. This effect was pronounced upon transfection and induction with DPP IR Mtx @Lipo NPs, particularly in comparison to non-transfected malignant breast cancer 4T1 cells. [Display omitted] • Novel self-assembled porphysomes nanosystem triggers chemo-photothermal therapy. • DPP IR Mtx @Lipo NPs showed enhanced cellular internalization and drug delivery. • Porphysomes showed an anti-neoplastic nature, which inhibits metastasis. • Upon transient transfection, DPP IR Mtx @Lipo NPs promotes apoptotic cell death. [ABSTRACT FROM AUTHOR]

Precision-based drug delivery via remote triggering is fast becoming an attractive therapeutic design and is highly useful in complicated clinical situations that may require accurate site-delivery of drug while reducing the risk of collateral damage to surrounding healthy tissue. Of the many strategies available to achieve these desirable effects, silica/gold nano-assemblies offers a practical means to achieving these aims. Herein, as a proof-of-concept, a silica nanocapsule passivated with a gold outer nanoshell had been fabricated to deliver Doxorubicin, and this nano-assembly can be remotely triggered via two-photon excitation (TPE), even under in vivo setting. A polyethylene glycol (PEG) layer as well as AS1411 DNA aptamer had also been grafted to the surface to improve homing specificity toward MDA-MB-231 breast cancer tissue. The assembly of silica/gold nanocapsules was characterized via TEM, FTIR, and UV-Vis to validate the the nanoconstruct. Upon TPE irradiation, a higher expression level of Annexin V and Caspase-3 was observed in both in vitro and in vivo animal models. A significant reduction in tumor size on mice model was noticed after 21 days, and these results had suggested a viable nano-sized design serving as remotely triggered drug release platform based on current well-established silica nanoparticulate methodologies.

Aptamer (Apt) is a kind of recognition molecule with excellent affinity and high specificity. Transmembrane glycoprotein mucin (MUC1) is an important tumor biomarker overexpressed in MCF-7 tumor cells. MUC1 Apt (Apt-M) could specifically target MCF-7 tumor cells. Ti3C2 nanosheets with high photothermal conversion efficiency were considered as a promising therapeutic nanoplatform for tumor therapy. Doxorubicin (DOX) is a common anti-tumor drug. Herein, a novel DOX/Ti3C2/Apt-M therapeutic nanoplatform was successfully fabricated, which could specifically target MCF-7 tumor cells. As expected, the temperature of DOX/Ti3C2/Apt-M therapeutic nanoplatform raised rapidly under laser irradiation. Meanwhile, chemotherapy was triggered through multimodal stimuli-responsive drug release from the DOX/Ti3C2/Apt-M therapeutic nanoplatform under acidic environment and laser-induced local high temperature. Encouragingly, the MCF-7 cell viability of DOX/Ti3C2/Apt-M with laser irradiation was only 26.9%. The tumor surface temperature of MCF-7 xenograft mice in the DOX/Ti3C2/Apt-M + Laser group rose to about 58.3 °C, which was significantly higher than other laser irradiation groups. The experiments in vitro and in vivo indicated that the DOX/Ti3C2/Apt-M therapeutic nanoplatform can rapidly accumulate in MCF-7 tumors with excellent active targeting properties, and display superior tumor suppressive ability through combination therapy. This work provides a new idea of targeted tumor therapy based on Ti3C2 nanosheets.

Background: As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect. Methods: CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay. Results: Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively. Conclusion: The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP. [ABSTRACT FROM AUTHOR]

Heat stimulation can promote osteoblast differentiation and bone formation. Combining photothermal therapy and chemotherapy is an effective strategy for treating rheumatoid arthritis (RA). Herein, we prepared chitosan/gelatin/β-glycerophosphate-melanin-methotrexate (CMM) hydrogel that could be used to perform simultaneous chemotherapy and photothermal therapy for patients with RA. The CMM solution was successfully converted to a gel state at body temperature. Due to intrinsic photothermal properties of melanin, CMM hydrogel exhibited effective temperature increase both in vitro and in vivo with increasing time of near-infrared (NIR) laser irradiation. After NIR laser irradiation, 50 % of methotrexate was rapidly released from the hydrogel within 3 h. Its release rate showed an instantaneous increase with additional NIR laser irradiation. After CMM hydrogel was injected directly into the paw joint of each collagen-induced arthritis (CIA) mouse followed by irradiation with a NIR laser (808 nm, 0.5 W/cm2, 3 min), swelling and redness at the inflamed area were significantly alleviated at 14 days after treatment. Micro-CT analysis confirmed that treated joints of mice were similar to normal joints. Hence, CMM hydrogel could be used as an attractive RA therapeutic agent for simultaneous chemo-photothermal therapy. [ABSTRACT FROM AUTHOR]

Chemo-photothermal therapy is one of the emerging therapies for treating triple-negative breast cancer. In this study, we have used ionotropic gelation method to fabricate chitosan and IR806 dye-based polyelectrolyte complex (CIR-PEx) nanoparticles. These nano-complexes were in size range of 125 ± 20 nm. The complexation of IR 806 dye with chitosan improved photostability, photothermal transduction, and showed excellent biocompatibility. Cancer cells treated with CIR-PEx NPs enhanced intracellular uptake within 5 h of incubation and also displayed mitochondrial localization. With the combination of CIR-PEx NPs and a chemotherapeutic agent (i.e. , mitoxantrone, MTX), a significant decline in cancer cell viability was observed in both 2D and 3D cell culture models. The chemo-photothermal effect of CIR-PEx NPs + MTX augmented apoptosis in cancer cells when irradiated with NIR light. Furthermore, when tested in the 4 T1-tumor model, the chemo-photothermal therapy showed a drastic decline in tumor volume and inhibited metastatic lung nodules. The localized hyperthermia caused by photothermal therapy reduced the primary tumor burden, and the chemotherapeutic activity of mitoxantrone further complemented by inhibiting the spread of cancer cells. The proposed chemo-photothermal therapy combination could be a promising strategy for treating triple-negative metastatic breast cancer. • The study shows the significance of chemo-photothermal combination therapy. • CIR-PEx NPs enhance the efficacy of mitoxantrone in cancer therapy. • The CIR-PEx NPs exhibit mucin binding potential for efficient cancer therapy. • Combination therapy enhances cell cytotoxicity in triple negative breast cancer. • CIR-PEx NPs with mitoxantrone prevents metastasis and splenomegaly. [ABSTRACT FROM AUTHOR]

Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer., Competing Interests: Declaration of competing interest The author declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Multifunctional nanoplatforms capable of simultaneously executing multimodal therapy and imaging functions are of great potentials for cancer theranostics. We present an elegantly designed, easy-to-fabricate poly(acrylic acid)/mesoporous calcium phosphate/mesoporous copper phosphate nanosphere (PAA/mCaP/mCuP NS) with outstanding pH/NIR-sensitive multimodal-synergic anti-tumor effects. Optimal porous PAA NS scaffolds were prepared at room temperature by balancing the intra-PAA polymer and polymer-solvents Lennard-Jones potentials in a water:isopropyl alcohol (IPA) mix-solvent. Subsequent sponging of Ca 2+ and Cu 2+ , and adsorption of PO 4 3- to the PAA template were achieved through exquisite electrostatic interactions among ions and the ionizable PAA side-chain in an aqueous environment. This forms the basis for the tumor microenvironment pH-triggered release of Cu 2+ to induce cuproptosis, as well as the photothermal effect originating from CuP, while Ca 2+ can enhance the nanoplatform's biocompatibility and can damage mitochondria when overloaded. Lastly, PAA/mCaP/mCuP NSs still exhibit high drug loading efficiency for doxorubicin (DOX), enabling chemotherapy. Satisfactory anti-tumor effects of these modalities, along with their synergistic effects, were verified both in vitro and in vivo, with the NSs demonstrating good biodegradation in the latter. The fabricated NS itself holds great promise as an anti-tumor nanomedicine, and the thorough mechanical insights into NS formation may inspire the design of next-generation multifunctional nanoplatforms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sujuan Zeng,1,&ast; Shiqi Liu,1,2,&ast; Yintao Lan,3 Ting Qiu,3 Mengyu Zhou,3 Weijian Gao,3 Wenyan Huang,1 Lihong Ge,1,4 Jian Zhang1,3 1Department of Pedodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong, People’s Republic of China; 2Department of Stomatology, Taihe Hospital, Institute of Oral Diseases, School of Dentistry, Hubei University of Medicine, Hubei, People’s Republic of China; 3Department of Biomedical Engineering, School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Guangzhou Medical University, Guangdong, People’s Republic of China; 4Department of Pediatric Dentistry, Stomatology Hospital of Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Lihong Ge Email jianzhang@gzhmu.edu.cn; gelh0919@126.comBackground: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment.Methods: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy.Results: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues.Conclusion: Our research provides a solid demonstration of the potential of DOX–AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.Keywords: mesoporous silica coated gold nanorods, photoacoustic imaging, chemo-photothermal therapy, oral squamous cell carcinoma

Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανβ3 y ανβ5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.

Malignant tumor is one of the major diseases with high morbidity and mortality. The purpose of this study is to prepare berberine hydrochloride (BH) in situ thermo-sensitive hydrogel based on glycyrrhetinic acid (GA) modified nano graphene oxide (NGO) (GA-BH-NGO-gel). NGO was taken as the photosensitizer, GA was taken as the target molecule, and BH was taken as the model drug. The physicochemical properties and anti-tumor activity in vivo and in vitro were also studied. This subject could provide a certain theoretical basis for the chemo-photothermal therapy combined treatment of malignant tumor. The release behavior of GA-BH-NGO-gel in vitro presented sustained and temperature-dependent drug release effect. The anti-tumor activity studies in vivo and in vitro had shown that GA-BH-NGO-gel had stronger anti-tumor activity, which could be targeting distributed to the tumor tissues. Moreover, the inhibitory effect of GA-BH-NGO-gel was enhanced when combined with 808 nm of laser irradiation. In this research, the chemo-photothermal combination therapy was applied into the tumor treatment, which may provide certain research ideas for the clinical treatment of malignant tumor. [ABSTRACT FROM AUTHOR]

Aim: To develop synergistic chemo-photothermal and ferroptosis therapy nanoparticles to improve the efficacy of treatment for esophageal cancer. Materials & methods: Fe3O4@PDA-HCPT nanoparticles (NPs) were constructed and characterized. Their synergistic antitumor effects were evaluated in EC1 and EC109 esophageal cancer cells as well as in esophageal cancer-bearing mice. Results:In vitro and in vivo experiments showed that Fe3O4@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties. The killing ability of tumor cells was significantly enhanced after irradiation. Conclusion: Synergistic application of the three therapies effectively inhibited tumor growth and exhibited potent antitumor effects, providing strong support for developing nanoparticles with synergistic antitumor effects of multiple therapies. Synergistic treatment with multiple therapies has been shown to be a promising strategy for cancer treatment. Here, the authors designed Fe3O4@PDA-HCPT NPs composed of Fe3O4, polydopamine and the chemotherapy drug 10-hydroxycamptothecin. The authors achieved synergistic antitumor treatment with chemo-photothermal and ferroptosis therapy guided by T2-weighted MRI. In vitro and in vivo experiments showed that Fe3O4@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties, which supports the development of relevant synergistic tumor therapies. [ABSTRACT FROM AUTHOR]