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Theragnostic platforms, which integrate therapeutic and diagnostic capabilities, have gained significant interest in drug research because of to their potential advantages. This study reports the development of a novel multifunctional nanoparticle carrier system based on poly(ᴅ,ʟ-lactic-co-glycolic acid) (PLGA) for the targeted delivery of the chemotherapeutic agent chlorambucil (CHL) and the imaging agent IR780. The approach in this study incorporates Pluronic F127-folate onto the PLGA nanoparticles, which enables targeted delivery to folate receptor-expressing cancer cells. The F127-folate@PLGA/CHL/IR780 nanoparticles were formulated using a nanoprecipitation technique, resulting in small size, high homogeneity, and negative surface charge. Importantly, the folate-targeted nanoparticles demonstrated enhanced uptake and cytotoxicity in folate receptor-positive cancer cell lines (MCF-7 and HepG-2) compared to folate receptor-negative cells (HEK 293). Additionally, the F127-folate@PLGA/CHL/IR780 nanoparticles exhibited a lower IC50 value against cancer cells than non-targeted F127@PLGA/CHL/IR780 nanoparticles. These findings suggest that the developed F127-folate@PLGA/CHL/IR780 nanoparticles hold promise as a theragnostic system for targeted cancer therapy and diagnosis, leveraging the advantages of PLGA, folate targeting, and the integration of therapeutic and imaging agents.

Yi Zhang,1 Dang Liu,2 Bin Qiao,3 Yuanli Luo,3 Liang Zhang,3 Yang Cao,3 Haitao Ran,3,* Chao Yang4,* 1Department of Ultrasound, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haitao Ran, Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 13512373563, Email ranhaitao@cqmu.edu.cn Chao Yang, Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China, Tel +86 13883095836, Email ychaof737@163.comPurpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.Keywords: Bi-DTPA, IR780, radiotherapy, tumor microenvironment hypoxia, photothermal therapy

IR780 iodide is a commercially available targeted near‐infrared contrast agent for in vivo imaging and cancer photodynamic or photothermal therapy, whereas the accumulation, dynamics, and retention of IR780 in biological tissue, especially in tumor is still under‐explored. Diffuse fluorescence tomography (DFT) can be used for localization and quantification of the three‐dimensional distribution of NIR fluorophores. Herein, a homemade DFT imaging system combined with tumor‐targeted IR780 was utilized for cancer imaging and pharmacokinetic evaluation. The aim of this study is to comprehensively assess the biochemical and pharmacokinetic characteristics of IR780 with the aid of DFT imaging. The optimal IR780 concentration (20 μg/mL) was achieved first. Subsequently, the good biocompatibility and cellar uptake of IR780 was demonstrated through the mouse acute toxic test and cell assay. In vivo, DFT imaging effectively identified various subcutaneous tumors and revealed the long‐term retention of IR780 in tumors and rapid metabolism in the liver. Ex vivo imaging indicated IR780 was mainly concentrated in tumor and lung with significantly different from the distribution in other organs. DFT imaging allowed sensitive tumor detection and pharmacokinetic rates analysis. Simultaneously, the kinetics of IR780 in tumors and liver provided more valuable information for application and development of IR780. [ABSTRACT FROM AUTHOR]

Theragnostics has become a popular term nowadays, since it enables both diagnosis and therapy at the same time while only using one carrier platform. Therefore, formulating a nanocarrier system that could serve as theragnostic agent by using simple techniques would be an advantage during production. In this project, we aimed to develop a nanocarrier that can be loaded with the chemotherapeutic medication chlorambucil and magnetic resonance imaging agents (e.g., iron oxide nanoparticles and near-infrared fluorophore IR780) for theragnostics. Poly(lactic-co-glycolic acid) was combined with the aforementioned ingredients to generate poly(vinyl alcohol)-based nanoparticles (NPs) using the single emulsion technique. Then the NPs were coated with F127 and F127-folate by simple incubation for five days. The nanoparticles have the hydrodynamic size of approx. 250 nm with negative charge. Similar to chlorambucil and IR780, iron oxide loadings were observed for all three kinds of NPs. The release of chlorambucil was quicker at pH 5.4 than at pH 7.4 at 37 °C. The F127@NPs and F127-folate@NPs demonstrated much greater cell uptake and toxicity up to 72 h after incubation. Our in vitro results of F127@NPs and F127-folate@NPs have demonstrated the ability of these systems to serve as medication and imaging agent carriers for cancer treatment and diagnostics, respectively.

Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy. [Display omitted] • CD39 blockade was utilized to strengthen the effect of photoimmunotherapy by regulating the ATP-adenosine axis. • An ingenious dissolving microneedle patch was designed for the intralesional delivery of CD39 blockade and immunogenic cell death inducer co-encapsulated solid lipid nanoparticles. • This system aroused a robust immune response against B16 and MC38 tumors via suppressing the CD39 expression on the surface of relevant immune cells and subsequently inducing DCs maturation, boosting antigen-specific lymphocytes infiltration, and reversing macrophages polarization. [ABSTRACT FROM AUTHOR]

Aim: The present investigation aimed to develop a chemo-free, nanophytosomal system to treat triple-negative breast cancer (TNBC) via a phyto–photo dual treatment strategy. Method: Size, shape, surface analysis, photoprovoked release profile, photothermal stability, (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay, apoptotic assay, DNA fragmentation, in vitro cellular uptake evaluation, mitochondrial membrane potential and caspase-3 assay, and photodynamic evaluation. Results: Biological experiments using MDA-MB-231 cells displayed dose-dependent synergistic anti-TNBC activity of PhytoS/Houttuynia cordata extract (HCE)/IR780 as compared with Phyto/HCE, PhytoS/IR780 and even more promising under laser treatment. Apoptotic assay and DNA fragmentation analysis also showed enhanced anti-TNBC effects. Investigation found that HCE acts via suppression of mitochondrial membrane potential and inducing caspase-3 activity in cells. Conclusion: Our findings suggested that photo-empowered phytotherapy can be employed effectively and safely against TNBC. [ABSTRACT FROM AUTHOR]

In the past decade, tumor treatment strategies have shifted from tumors to the immune system of tumor patients. NIR laser-induced photothermal therapy can not only generate heat or reactive oxygen species to kill tumors but also induce immunogenic cell death and activate the overall antitumor immune response. The ICD process is usually accompanied by autophagosome formation, which contains tumor-associated antigens. However, the fusion of autophagosome and lysosome impairs antigens, weakening the antitumor immune response. Thus, administration with autophagy terminal inhibitors could be a compensatory strategy. In this work, we prepared a thermally sensitive liposome drug delivery system containing the photothermal agent IR780 and autophagy inhibitor HCQ (IR780/HCQ-Lip). IR780/HCQ-Lip has a uniform particle size distribution and good photodynamic and photothermal properties. The inhibition of autophagy enhanced the phototherapy effect. Compared with the survival rate of 4T1 cells being treated with IR780-Lip phototherapy alone (36.87%), the survival rate of the IR780/HCQ-Lip group decreased to 3.71%. IR780/HCQ-Lip caused a massive accumulation of autophagosomes, promoted the maturation of dendritic cells (DCs), and enhanced the infiltration of intratumoral T cells. In addition, IR780/HCQ-Lip produced a systemic immune response and also showed good inhibition of distal tumor growth under laser action in distal tumor experiments. Thus, IR780/HCQ-Lip exhibited a promising combination therapy for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Due to the high efficiency and noninvasive nature, photodynamic therapy (PDT) and photothermal therapy (PTT) have received increasing attention as a potential tumor treatment approach. However, extreme hypoxia and overexpressed glutathione (GSH) in tumor cells restrict therapeutic efficacy. In this contribution, a multifunctional nanozyme of IR780-HCuS@MnO2 (I/C@M) was synthesized for tumor synergistic PPT and enhanced PDT. In the constructed nanozymes, hollow mesoporous copper sulfide (HCuS) as the core, the near-infrared dye IR780 iodide was loaded for PDT and PTT, and manganese dioxide (MnO2) was coated as a "gatekeeper" to prevent drug leakage on the surface. Under pH stimulation, MnO2 disintegrated to release IR780, producing exogenous reactive oxygen species (ROS) for PDT after under near-infrared (NIR) irritation. With the assistance of NIR, IR780 and HCuS can be used for PTT, and the double photothermal effect is higher than that of single therapy. In addition, MnO2 can amplify intracellular oxidative stress by depleting abundant GSH and H2O2 in the tumor, which will further enhance the PDT of IR780. Importantly, three treatments can be performed at the same time with only one laser irradiation. The excellent therapeutic effect of facilitating apoptosis and suppressing tumor growth was generally evaluated and validated both in vivo and in vitro. In summary, our work developed a potential nanomedicine for the synergistic treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Currently, the use of nanotechnology to repurpose traditional drugs has emerged as a promising strategy for cancer treatment. Quercetin (Qu), a chemotherapy molecule, has excellent antitumor activity, and IR780, a photosensitizer, possesses sound tumor phototherapy effects. However, both compounds have poor water solubility and other drawbacks that hinder their extensive clinical applications. To effectively utilize two molecules in the fight against cancer, a new multifunctional chemical-phototherapy nanoplatform with tumor target and glutathione (GSH) response was designed. By modifying hyaluronic acid (HA), the amphiphilic molecule carrying biotin and IR780 was obtained, which self-assembled to load the antitumor active molecule Qu, namely Qu@BHSI. In addition to addressing the hydrophobic issue of Qu and IR780, the prepared nanoparticles can rapidly release Qu with high concentrations of GSH present and generate heat and cytotoxic reactive oxygen species (ROS) under near-infrared light. The biological function research showed that Qu@BHSI nanoparticles had the ability to suppress the growth of A549 cells, induce cell apoptosis, stimulate ROS production in zebrafish, and inhibit angiogenesis in transgenic zebrafish. The construction of nanosystems provides new or alternative strategies and approaches for effectively repurposing classical drug molecules including photosensitizers and chemotherapy drugs.

Purpose: The effect of monotherapy in cancer is frequently influenced by the tumor's unique hypoxic microenvironment, insufficient drug concentration at the treatment site, and tumour cells' increased drug tolerance. In this work, we expect to design a novel therapeutic nanoprobe with the ability to solve these problems and improve the efficacy of antitumor therapy. Methods: We have prepared a hollow manganese dioxide nanoprobes loaded with photosensitive drug IR780 for the photothermal/photodynamic/chemodynamic co-therapy of liver cancer. Results: The nanoprobe demonstrates efficient thermal transformation ability under a single laser irradiation, and under the synergistic influence of photo heat, accelerates the Fenton/ Fenton-like reaction efficiency based on Mn2+ ions to produce more ·OH under the synergistic effect of photo heat. Moreover, the oxygen released under the degradation of manganese dioxide further promotes the ability of photosensitive drugs to produce singlet oxygen (ROS). The nanoprobe has been found to efficiently destroy tumour cells in vivo and in vitro experiments when used in combination with photothermal/photodynamic/ chemodynamic modes of treatment under laser irradiation. Conclusion: In all, this research shows that a therapeutic strategy based on this nanoprobe could be a viable alternative for cancer treatment in the near future. [ABSTRACT FROM AUTHOR]

A certain proportion of non-Hodgkin’s lymphoma (NHL) patients will relapse after standard chemotherapy with an anthracycline-based regimen. Therefore, identifying novel therapeutic methods are a vital topic for improving therapeutic effects of NHL. IR780, a near-infrared dye, can be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed an effective nanoparticle system for carrying IR780 and Idarubicin, thus hoping to combine PTT/PDT and chemotherapy to treat NHL. This nanosystem consisted of PEG-b-PTMC nanoparticles. IR780 and Idarubicin (IDA) were loaded separately into PEG-b-PTMC nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PEG-b-PTMC nanoparticle (IR780 + IDA NPs) showed strong PTT/PDT efficacy with high-efficiency endocytosis and increasing reactive oxygen species (ROS) generation. By the evaluation of the photothermal conversion, we can confirm that IR780 + IDA NPs has been successfully delivered and exhibited significant synergistic effects on inhibiting cell proliferation in Raji and U937 cells. In vivo experiments have also demonstrated that IR780 + IDA NPs has a significant inhibitory effect on lymphoma and has a good biological safety. In summary, we put forward a therapeutic strategy for NHL treatment by combining PTT/PDT and chemotherapy.

Acute thrombosis is a leading cause of mortality and morbidity worldwide. Pharmacological thrombolysis relies on plasminogen activators (PAs), which are associated with major side effects including potentially fatal bleeding. Alternative therapeutic options that do not rely on PAs are urgently required. Here, the efficacy of targeted photothermal therapy is evaluated for thrombolysis using liposomes loaded with IR780 dye, which release heat upon near‐infrared (NIR) irradiation. Liposomes targeted to activated platelets—one of the main components of thrombi—accumulate preferentially in thrombi both in vitro and in vivo compared to non‐targeted controls. In a mouse model of thrombosis, targeted IR780 immunoliposomes (Tar‐IR‐L) produce ≈12 °C average local temperature increase upon NIR irradiation (5 min, 1 W cm−2). This causes a significant reduction in clot area compared to controls treated with non‐targeted liposomes or phosphate‐buffered saline, which only increase local temperature slightly (6 and 3 °C) when irradiated. Co‐loading a low‐dose single chain urokinase plasminogen activator (scuPA) to targeted IR780 liposomes (Tar‐scuPA‐IR‐L) does not result in a superior thrombolytic effect, which indicates that photothermal therapy alone may allow thrombolysis without the need for fibrinolytic drugs. This approach may prevent potential bleeding complications, promising a safer alternative to current pharmacological approaches. [ABSTRACT FROM AUTHOR]

Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm 2 ). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E, Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kai Wu reports was provided by National Natural Science Foundation of China (No. 82204632). If there are other authors, they 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 B.V. All rights reserved.)

Laryngeal cancer is the most common malignant tumor for which there is still a lack of effective treatment. Traditional radiotherapy, chemotherapy, and surgery all have significant side effects. Therefore, multifunctional collaborative therapeutic nanoplatforms are attractive to patients with laryngeal cancer. In this study, a near-infrared responsive IR780-modified MXene (Ti3C2) nanosheet was proposed as a strategy for targeted therapy to achieve the synergistic functions of photothermal (PTT) therapy, photodynamic (PDT) therapy and mitochondrial pathway apoptosis. Electron spin resonance results showed that Ti3C2@IR780 could produce singlet linear oxygen for PDT. Molecular biology studies showed that Ti3C2@IR780 had the outstanding ability to generate ROS to disrupt mitochondrial function, resulting in apoptosis of cancer cells up to 60.51%. In vivo experiments showed that Ti3C2@IR780 could effectively aggregate at tumor sites. The temperature of the tumor region could reach 63.7 °C in the presence of near-infrared light. Tumor growth was inhibited by 92% during the treatment, and there was no recurrence. Results of the sections showed an 88.1% reduction in microtumor vascularity with Ti3C2@IR780 treatment for 21 days compared to the control group. These findings suggest that this multifunctional nanoplatform with synergistic NIR-sensitive properties can effectively inhibit tumor growth, providing an ideal strategy for cancer treatment.

Abstract Background RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function. Results In this study, we reported a green technology of “disassembly-reassembly” to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing IR780@rRBC NPs with IR780@RBC NPs and free IR780 as controls. The results demonstrated the superiority of IR780@rRBC NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with IR780@rRBC and free IR780. Conclusions The reported “disassembly-reassembly” strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles . Graphic abstract

Breast cancer, the predominant malignancy afflicting women, continues to pose formidable challenges despite advancements in therapeutic interventions. This study elucidates the potential of phototherapy, comprising both photothermal and photodynamic therapy (PTT/PDT), as a novel and promising modality. To achieve this goal, we devised liposomes coated with macrophage cell membranes including macrophage-associated membrane proteins, which have demonstrated promise in biomimetic delivery systems for targeting tumors while preserving their inherent tumor-homing capabilities. This integrated biomimetic delivery system comprised IR780, NONOate, and perfluorocarbon. This strategic encapsulation aims to achieve a synergistic combination of photodynamic therapy (PDT) and reactive nitrogen species (RNS) therapy. Under near-infrared laser irradiation at 808 nm, IR780 demonstrates its ability to prolifically generate reactive oxygen species (ROS), including superoxide anion (O2•−), singlet oxygen, and hydroxyl radical (·OH). Simultaneously, NONOate releases nitric oxide (NO) gas upon the same laser irradiation, thereby engaging with IR780-induced ROS to facilitate the formation of peroxynitrite anion (ONOO−), ultimately inducing programmed cell death in cancer cells. Additionally, the perfluorocarbon component of our delivery system exhibits a notable affinity for oxygen and demonstrates efficient oxygen-carrying capabilities. Our results demonstrate that IR780-NO-PFH-Lip@M significantly enhances breast cancer cell toxicity, reducing proliferation and in vivo tumor growth through simultaneous heat, ROS, and RNS production. This study contributes valuable insights to the ongoing discourse on innovative strategies for advancing cancer therapeutics. • A biomimetic drug delivery system, designated as IR780-NO-PFH-Lip@M was developed. • Enhanced tumor cell affinity and cellular uptake efficiency were achieved. • Superior therapeutic efficacy by combining cytotoxic from ROS and ONOO- was shown. • Excellent biocompatibility and a reduced side effect profile were achieved. [ABSTRACT FROM AUTHOR]

Due to the significant loss in the effectiveness of conventional antibiotics against MDR bacterial strains, effective antibacterial therapy strategies are urgently needed. The aim of this study is to design a novel theranostic IR780 encapsulated, nanosized, radiolabeled ethosomes for effective Photodynamic (PDT)/photothermal therapy (PTT) and concurrent imaging of infections and to assess the role of the surface charge of theranostic ethosomes on effectiveness. Low aqueous solubility, ROS yield, and penetration ability of IR 780 can be enhanced by encapsulation in ethosomes, and also concurrent imaging can be achieved by designing nanotheranostic ethosomes. IR780 encapsulated, 99mTc-labeled, neutral IR780-PL100H:PEG2000:DTPA-PE and positively charged IR780-PL100H:SA:PEG2000:DTPA-PE ethosomes were designed for scintigraphic and near-infrared (NIR) imaging and PDT/PTT of bacterial infections. Their characterization and in vitro release profiles were determined. The physical stability of formulations was evaluated for 3 months at 25°C and 4°C. Their thermal performance and antibacterial activity against S. aureus and E. coli were evaluated by NIR irradiation (808 nm, 1 Wcm-2) for 2 min. Ethosomes exhibited suitable particle sizes (~200 nm, PDI: 0.12), zeta potentials (-25 to -28mV), encapsulation efficiencies (81-84%), release profiles, and found stable for 1 month at 4°C. Both ethosomes exhibited significant thermal enhancements by NIR light application. Although neutral ethosomes showed a potent antibacterial effect, positively-charged IR780-PL100H:SA:PEG2000:DTPA-PE exhibited higher PDT/PTT antibacterial efficacy against S. aureus and E. coli under NIR irradiation. Therefore, IR780 nanotheranostic ethosomes were found potentially effective for imaging, and PDT/PTT antibacterial and positive surface charge could contribute to higher PDT/PTT antibacterial efficacy. [ABSTRACT FROM AUTHOR]

Background: Blocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity. Methods: IR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy. Results: In vitro , US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo , at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects. Conclusion: The combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC. [ABSTRACT FROM AUTHOR]

Gold core silica shell (AuMSS) nanorods present excellent physicochemical properties that allow their application as photothermal and drug delivery agents. Herein, AuMSS nanorods were dual‐functionalized with Polyethylene glycol methyl ether (PEG‐CH3) and Gelatin (GEL) to enhance both the colloidal stability and uptake by HeLa cancer cells. Additionally, the AuMSS nanorods were combined for the first time with IR780 (a heptamethine cyanine molecule) and its photothermal and photodynamic capacities were determined. The obtained results reveal that the encapsulation of IR780 (65 µg per AuMSS mg) increases the photothermal conversion efficiency of AuMSS nanorods by 10%, and this enhanced heat generation was maintained even after three irradiation cycles with a NIR (808 nm) laser. Moreover, the IR780‐loaded AuMSS/T‐PEG‐CH3/T‐GEL presented ≈2‐times higher uptake in HeLa cells, when compared to the non‐coated counterparts, and successfully mediated the light‐triggered generation of reactive oxygen species. Overall, the combination of photodynamic and photothermal therapy mediated by IR780‐loaded AuMSS/T‐PEG‐CH3/T‐GEL nanorods effectively promoted the ablation of HeLa cancer cells. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.

Wenjing Pei,1,2 Biying Huang,1,2 Sijie Chen,1,2 Long Wang,3 Yan Xu,1,2 Chengcheng Niu1,2 1Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Chengcheng NiuDepartment of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaEmail niuchengcheng@csu.edu.cnBackground: Traditional nanoparticle-based drug delivery systems suffer from several limitations, such as easy clearance from blood and inaccurate targeting.Materials and Methods: Here, we developed platelet membrane-coated nanoparticles (PM-NPs) to improve the precise delivery of drugs to tumor sites and enable a more efficient photothermal therapy (PTT) treatment.Results: Mimicking the natural platelet membrane, nanoparticles containing drugs and photothermal agents were not recognized and cleared by the immune system; they could circulate in the blood for a long time and accumulate more efficiently at the tumor site, thus releasing more antitumor drugs and achieving better PTT effects. It is worth mentioning that, in this study, we found that tumors in mice treated with the platelet-mimicking nanoparticles were completely eliminated without recurrence during the observation period (up to 18 days).Conclusion: This study provides a new strategy to design delivery systems of drugs or photothermal agents, whether in biotherapy or other fields.Keywords: platelet-mimicking, drug delivery, IR780, doxorubicin, chemo-photothermal therapy

Sijie Chen,1– 3 Biying Huang,1,2 Wenjing Pei,1,2 Long Wang,4 Yan Xu,1,2 Chengcheng Niu1,2 1Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Ultrasound Diagnosis, Changsha Central Hospital, Nanhua University, Changsha, Hunan 410014, People’s Republic of China; 4Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of ChinaCorrespondence: Chengcheng NiuDepartment of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaEmail niuchengcheng@csu.edu.cnBackground: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment.Methods and Materials: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding.Results: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect.Conclusion: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.Keywords: IR780, mitochondria-targeting, perfluorocarbon, photodynamic therapy, photothermal therapy

BackgroundBlocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity.MethodsIR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy.ResultsIn vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects.ConclusionThe combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.

IR780 is a near-infrared fluorescent dye, which can be applied as a photosensitizer in photodynamic (PDT) and photothermal (PTT) therapies and as a biodistribution tracer in imaging techniques. We investigated the growth and migration inhibition and mechanism of death of breast tumor cells, MCF-7 and MDA-MB-231, exposed to polymeric nanocapsules (NC) comprising IR780 covalently linked to the biodegradable polymer PLA (IR-PLA) and IR780 physically encapsulated (IR780-NC) in vitro. Both types of NC had mean diameters around 120 nm and zeta potentials around −40 mV. IR-PLA-NC was less cytotoxic than IR780 NC to a non-tumorigenic mammary epithelial cell line, MCF-10A, which is an important aspect of selectivity. Free-IR780 was more cytotoxic than IR-PLA-NC for MCF-7 and MDA-MB-231 cells after illumination with a 808 nm laser. IR-PLA NC was effective to inhibit colony formation (50%) and migration (30–40%) for both cancer cell lines. MDA-MB-231 cells were less sensitive to all IR780 formulations compared to MCF-7 cells. Cell uptake was higher with IR-PLA-NC than with IR780-NC and free-IR780 in both cancer cell lines (p

Multidrug-resistant (MDR) bacterial strains have emerged and weakened the therapeutic effects of antibacterial drugs. Sonodynamic therapy (SDT) takes advantage of noninvasiveness and deep tissue-penetrating features and has been rejuvenated to combat MDR bacteria and their biofilm-associated infections. To improve the efficacy of antibacterial SDT, we first developed IR780-based PLGA nanoparticles as sonosensitizers for high-frequency ultrasound (US)-monitored antibacterial SDT of MRSA myositis by therapeutic low-frequency US. In this study, the developed shell-core-structured IR780@PLGA nanoparticles were designed with a polymer shell PLGA with the sonosensitizer IR780 loaded on. High-frequency diagnostic US was introduced to monitor the sonotherapeutic progression of bacterial myositis by therapeutic low-frequency US. Importantly, the in vitro and in vivo results confirmed that IR780@PLGA nanoparticles combined with US irradiation possess high efficiency for antibacterial therapy. This approach provides a simple and efficient strategy to monitor and combat MDR bacterial infection.

Theragnostic platforms, which integrate therapeutic and diagnostic capabilities, have gained significant interest in drug research because of to their potential advantages. This study reports the development of a novel multifunctional nanoparticle carrier system based on poly(ᴅ,ʟ-lactic- co -glycolic acid) (PLGA) for the targeted delivery of the chemotherapeutic agent chlorambucil (CHL) and the imaging agent IR780. The approach in this study incorporates Pluronic F127-folate onto the PLGA nanoparticles, which enables targeted delivery to folate receptor-expressing cancer cells. The F127-folate@PLGA/CHL/IR780 nanoparticles were formulated using a nanoprecipitation technique, resulting in small size, high homogeneity, and negative surface charge. Importantly, the folate-targeted nanoparticles demonstrated enhanced uptake and cytotoxicity in folate receptor-positive cancer cell lines (MCF-7 and HepG-2) compared to folate receptor-negative cells (HEK 293). Additionally, the F127-folate@PLGA/CHL/IR780 nanoparticles exhibited a lower IC 50 value against cancer cells than non-targeted F127@PLGA/CHL/IR780 nanoparticles. These findings suggest that the developed F127-folate@PLGA/CHL/IR780 nanoparticles hold promise as a theragnostic system for targeted cancer therapy and diagnosis, leveraging the advantages of PLGA, folate targeting, and the integration of therapeutic and imaging agents., Competing Interests: Authors confirm that there is no conflict of interest related to the article., (Copyright © 2024, Pham et al.)

Background: RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function. Results: In this study, we reported a green technology of "disassembly-reassembly" to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing IR780@rRBC NPs with IR780@RBC NPs and free IR780 as controls. The results demonstrated the superiority of IR780@rRBC NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with IR780@rRBC and free IR780. Conclusions: The reported "disassembly-reassembly" strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles. [ABSTRACT FROM AUTHOR]

A novel strategy called "two‐stage dual‐synergistic tumor therapy (TDTT)," which combines photothermal therapy with infinite coordination polymers (ICPs) chemotherapy at the first stage in the short term and two drugs of ICPs synergistic chemotherapy (coordinated dual drugs chemotherapy) at the second stage in the long term, is proposed. This strategy is achieved by preparing IR780‐loaded hyaluronic acid (HA) encapsulated gossypol–Fe(III)–epigallocatechin gallate (EGCG) ICP nanoparticles (HA@IRGFE ICP NPs), which have IR780 inclusions, a natural gossypol, and EGCG coordinated with Fe3+ framework, and a HA shell. It is found that the HA@IRGFE ICP NPs' diameter is 120.0 ± 39.5 nm and has tumor‐targeting ability and can be rapidly released in tumor environment. Their photothermal conversion efficiency is greatly improved to 47.8%, and the total combination index of TDTT is 0.38, which indicates an excellent synergistic therapy result. These HA@IRGFE ICP NPs show low toxicity with a high tolerated dose (30.0 mg kg−1), a high tumor inhibition rate of 98.7%, and a very low tumor recurrence rate over 60 days (12.5%) with TDTT strategy, indicating their great potential applications in the field of tumor therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] Currently, the use of nanotechnology to repurpose traditional drugs has emerged as a promising strategy for cancer treatment. Quercetin (Qu), a chemotherapy molecule, has excellent antitumor activity, and IR780, a photosensitizer, possesses sound tumor phototherapy effects. However, both compounds have poor water solubility and other drawbacks that hinder their extensive clinical applications. To effectively utilize two molecules in the fight against cancer, a new multifunctional chemical-phototherapy nanoplatform with tumor target and glutathione (GSH) response was designed. By modifying hyaluronic acid (HA), the amphiphilic molecule carrying biotin and IR780 was obtained, which self-assembled to load the antitumor active molecule Qu, namely Qu@BHSI. In addition to addressing the hydrophobic issue of Qu and IR780, the prepared nanoparticles can rapidly release Qu with high concentrations of GSH present and generate heat and cytotoxic reactive oxygen species (ROS) under near-infrared light. The biological function research showed that Qu@BHSI nanoparticles had the ability to suppress the growth of A549 cells, induce cell apoptosis, stimulate ROS production in zebrafish, and inhibit angiogenesis in transgenic zebrafish. The construction of nanosystems provides new or alternative strategies and approaches for effectively repurposing classical drug molecules including photosensitizers and chemotherapy drugs. [ABSTRACT FROM AUTHOR]

Beibei Ma,1,* Jie Sheng,1,2,* Ping Wang,1 Zhongying Jiang,1,2 Entomack Borrathybay31College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, People’s Republic of China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, People’s Republic of China; 3College of Biology and Geography Sciences, Yili Normal University, Yining, Xinjiang, 835000, People’s Republic of China*These authors contributed equally to this work Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment.Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis.Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ϵ-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs).Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes.Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.Keywords: phototherapy, hypoxia-activated chemotherapy, IR780, tirapazamine, antitumor immune responsive, metastasis

Ying Liu, Peiwen Huang, Xuefeng Hou, Fei Yan, Zifei Jiang, Jiangpei Shi, Xingmei Xie, Junyi Shen, Qiangyuan Fan, Zhi Wang, Nianping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of ChinaBackground: Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin–phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer.Methods: CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice.Results: CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.Keywords: curcumin, IR780, oral drug delivery, lung metastasis of breast cancer, photo/chemotherapy

Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice. [ABSTRACT FROM AUTHOR]

As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 (IR780@Td) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the IR780@Td shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of IR780@Td nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in IR780@Td group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in IR780@Td group. Under near-infrared laser irradiation, the intravenous administration of IR780@Td promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment. Unlabelled Image • Atetrahedral DNA nanostructure (Td) was used toload hydrophobic IR780 (IR780@Td) by electrostatic binding. • The water solubility and photo stability of IR780 have been greatly improved. • The nanostructure of Td is proved important to obtain IR780 nanoparticles with EPR effect. • The PTT/PDT efficiency of IR780 are improved in IR780@Td group. • IR780@Td shows specific tumor imaging and enhanced anti-tumor effect. [ABSTRACT FROM AUTHOR]

Theragnostics has become a popular term nowadays, since it enables both diagnosis and therapy at the same time while only using one carrier platform. Therefore, formulating a nanocarrier system that could serve as theragnostic agent by using simple techniques would be an advantage during production. In this project, we aimed to develop a nanocarrier that can be loaded with the chemotherapeutic medication chlorambucil and magnetic resonance imaging agents (e.g., iron oxide nanoparticles and near-infrared fluorophore IR780) for theragnostics. Poly(lactic- co -glycolic acid) was combined with the aforementioned ingredients to generate poly(vinyl alcohol)-based nanoparticles (NPs) using the single emulsion technique. Then the NPs were coated with F127 and F127-folate by simple incubation for five days. The nanoparticles have the hydrodynamic size of approx. 250 nm with negative charge. Similar to chlorambucil and IR780, iron oxide loadings were observed for all three kinds of NPs. The release of chlorambucil was quicker at pH 5.4 than at pH 7.4 at 37 °C. The F127@NPs and F127-folate@NPs demonstrated much greater cell uptake and toxicity up to 72 h after incubation. Our in vitro results of F127@NPs and F127-folate@NPs have demonstrated the ability of these systems to serve as medication and imaging agent carriers for cancer treatment and diagnostics, respectively., Competing Interests: The authors confirm that there is no conflict of interest related to the article., (Copyright © 2024, Dang-Luong et al.)

Dan Wang,1,* Sipei Zhang,1,* Tao Zhang,1 Guoyun Wan,1 Bowei Chen,1 Qingqing Xiong,2 Jie Zhang,3 Wenxue Zhang,4 Yinsong Wang1 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, 2Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, 3Surgery Department, 4Radiotherapy Department, Tianjin Medical University General Hospital, Tianjin, China *These authors contributed equally to this work Abstract: IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy. Keywords: hepatocellular carcinoma, IR780, paclitaxel, combination therapy, nanoparticle

[Display omitted] • A novel photo-effective NIR light-responsive nanosystem was assembled. • The nanosytem produced a large temperature increase upon NIR laser exposure. • The nanosystem produced high levels of singlet oxygen upon NIR laser exposure. • The phototherapy mediated by the nanosystem reduced cancer cells viability to 21% Nanomaterials with near infrared light absorption can mediate an antitumoral photothermal-photodynamic response that is weakly affected by cancer cells' resistance mechanisms. Such nanosystems are commonly prepared by loading photosensitizers into nanomaterials displaying photothermal capacity, followed by functionalization to achieve biological compatibility. However, the translation of these multifunctional nanomaterials has been limited by the fact that many of the photosensitizers are not responsive to near infrared light. Furthermore, the reliance on poly(ethylene glycol) for functionalizing the nanomaterials is also not ideal due to some immunogenicity reports. Herein, a novel photoeffective near infrared light-responsive nanosystem for cancer photothermal-photodynamic therapy was assembled. For such, dopamine-reduced graphene oxide was, for the first time, functionalized with sulfobetaine methacrylate-brushes, and then loaded with IR780 (IR780/SB/DOPA-rGO). This hybrid system revealed a nanometric size distribution, optimal surface charge and colloidal stability. The interaction of IR780/SB/DOPA-rGO with near infrared light prompted a temperature increase (photothermal effect) and production of singlet oxygen (photodynamic effect). In in vitro studies, the IR780/SB/DOPA-rGO per se did not elicit cytotoxicity (viability > 78 %). In contrast, the combination of IR780/SB/DOPA-rGO with near infrared light decreased breast cancer cells' viability to just 21 %, at a very low nanomaterial dose, highlighting its potential for cancer photothermal-photodynamic therapy. [ABSTRACT FROM AUTHOR]

Abstract Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine–glycine–aspartic acid–cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron‐sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near‐infrared (NIR, λ = 700–1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.

Photodynamic therapy (PDT) has emerged as an efficient approach for non-invasive cancer treatment. However, organic small-molecule photosensitizers are often associated with defects in hydrophobicity, poor photostability, and aggregation-caused quenching, which limit their application. Usually, the carrier-assisted drug delivery system is a common strategy to solve the above obstacles, but additional carrier material could increase the risk of potential biological toxicity. The carrier-free drug delivery system with easy preparation and high drug-loading capability is proposed subsequently as a potential strategy to develop the clinical use of hydrophobic drugs. Herein, we rationally designed three IR780-based carrier-free nanosystems formed by carbon/disulfide/diselenide bond conjugated IR780-based homodimers. The IR780-based homodimers could self-assemble to form nanoparticles (DC-NP, DS-NP, DSe-NP) and exhibited higher reactive oxygen species generation capability and photostability than free IR780, in which DSe-NP with 808 nm laser irradiation performed best and resulted in the strongest cytotoxicity to 4T1 cells. Meanwhile, the glutathione consumption ability of DSe-NP boosted its PDT effect and then induced excessive oxidative stress of 4T1 cells, increasing antitumor efficacy by enhancing immunogenic cell death further. In tumor-bearing mice, DSe-NP displayed obvious tumor site accumulation, which obviously inhibited tumor growth and metastasis, and enhanced the immunological effect by effectively inducing dendritic cells to mature and activating T lymphocytes and natural killer cells. In summary, our study presented an IR780-based carrier-free nanodelivery system for a combination of PDT and immunity therapy and established expanding the application of organic small-molecule photosensitizers by an approach of carrier-free drug delivery system.

Exosomes (EXOs) are considered natural nanoparticles which have been widely used as carriers for the treatment and diagnosis of various diseases. However, due to the non-specific uptake, the unmodified EXOs cannot effectively deliver the vector to the target site. In this study, we used pDisplay vector to engineer Glypican-3 (GPC3) single-chain scFv antibody to the exosome surface, and the effect of engineered exosomes on the proliferation and migration of hepatocellular carcinoma (HCC) cells was determined by a series of in vitro experiments as well as in vivo mouse xenograft model and PDX model. Furthermore, we established an improved delivery system by engineering single-chain scFv antibody against GPC3 on the EXO surface for a more efficient HCC targeting. Moreover, the delivery system was loaded with IR780 and Lenvatinib for a combination of thermotherapy and chemotherapy. Our results revealed that the antibody-engineered exosomes enabled rapid imaging of HCC xenograft models post IR780 loading and showed significant anti-tumor photothermal therapy (PTT) effects after irradiation. Since dual loading of IR780 and Lenvatinib in exosomes required only a single injection and had a maximal efficacy against cancer cells, our findings highlight the clinical application of using GPC3 single-chain scFv antibody-engineered exosomes loaded with IR780 and Lenvartinib to achieve the imaging and the treatment of HCC from the combined effect of IR780-induced PTT and Lenvatinib-induced chemotherapy., Competing Interests: None., (AJCR Copyright © 2023.)

The near-infrared dye, IR780 iodide, has been utilized in photodynamic therapy (PDT) and photothermal therapy (PTT). However, the hydrophobicity and photosensitivity of IR780 limit its further applications in biomedical fields. Herein, the hydrophilic sericin was modified with hydrophobic cholesterol to form an amphiphilic macromolecular conjugate (Ser-Chol). The tumor-targeting agent, folic acid (FA), was further linked to the conjugate (FA-Ser-Chol). The IR780 could be encapsulated into such amphiphilic macromolecule to form stable micelles (FA-Ser-Chol/IR780) by self-assembly, and the solubility and photo-stability of IR780 were greatly improved. The FA-Ser-Chol/IR780 micelles could be efficiently absorbed by FA-positive gastric cancer cells (BGC-823) through FA receptors, while the uptake micelles showed remarkable PDT and PTT cytotoxicity towards BGC-823 cells under laser irradiation of 808 nm. Therefore, FA-Ser-Chol micelles may serve as a promising IR780 carrier for PDT and PTT therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract IR780 is a near infrared (NIR) dye with a huge potential to be applied in cancer phototherapy and imaging. However, IR780 poor water solubility and acute cytotoxicity limit its direct use in cancer theragnostic. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was used, for the first time, in the preparation of polymeric nanoparticles (HPN) encapsulating IR780 aimed to be applied in breast cancer therapy. Furthermore, HPN co-encapsulating IR780 and Doxorubicin (DOX) were also produced in order to further enhance the therapeutic effectiveness of this nanoformulation. The results revealed that HPN were able to successfully encapsulate IR780 (IR-HPN) and the IR780-DOX combination (IR/DOX-HPN). Furthermore, the encapsulation of IR780 in HPN improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential, as well as its cytocompatibility. The 2D in vitro cell uptake studies demonstrated that the nanostructures displayed a higher internalization by breast cancer cells than by normal cells. In addition, the assays performed in 3D in vitro models of breast cancer revealed that HPN can penetrate into spheroids. Furthermore, the 3D in vitro studies also demonstrated that the combined application of IR-HPN and NIR light was unable to induce cytotoxicity on spheroids. In contrast, IR/DOX-HPN produced a decrease on spheroids cells' viability, and their combination with NIR light induced an even stronger therapeutic effect, thus revealing the potential of these nanoparticles for cancer chemo-phototherapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Schematic design of Lip(IR780&TPZ). The drug delivery platform can be loaded with both hydrophilic and lipophilic cargos, such as the chemical drug tirapazamine (hydrophilic) and the photo-thermal agent IR780 (lipophilic). When the liposomes are exposed to laser irradiation, the phospholipid membrane ruptures, and tirapazamine is released. Tirapazamine causes DNA double-strand breaks and chromosome aberrations. Highlights • Lip (IR780&TPZ) combines PDT therapy with hypoxia-responsive modality. • Lip(IR780&TPZ) could cause cell death by generating ROS under laser irradiation. • Lip (IR780&TPZ) shows great antitumor efficacy. Abstract Photodynamic therapy (PDT) as a promising noninvasive and effective treatment modality has been clinically approved for cancer therapy. However, the poor selectivity of tumor and hypoxia-induced resistance constrain PDT efficacy immensely. To further enhance PDT's potency, we developed a drug delivery system based on liposome combining PDT and chemotherapeutics. The lipophilic IR780 was loaded into the lipid bilayer while hydrophilic chemotherapeutic agent tirapazamine (TPZ) was encapsulated in the hydrophilic core. IR780 could generate reactive oxygen species and hypoxic microenvironment in local site because of the continuous consumption of oxygen, resulting in the TPZ encapsulated in the aqueous liposome chamber brings out TPZ radicals to cause DNA double-strand breaks and chromosome aberrations. In vivo studies demonstrated that the liposomes which encapsulate IR780 and TPZ showed great antitumor efficacy via combining photodynamic therapy with chemotherapy. Therefore, the investigation combines PDT and hypoxia-activated chemotherapy from the TPZ. It is a simple but effective liposome platform to achieve multiple synergistic antitumor efficacy and shows potential for clinical use. [ABSTRACT FROM AUTHOR]

Effective endosomal escape is required for practical application of nucleic acid therapeutics. In this study, we prepared siRNA micelleplexes with photothermally triggered endosomal escape and improved gene silencing activity in vitro. The micelleplexes were prepared from cholesterol‐modified and CXCR4‐inhibiting poly(amido amine)s (PAMD‐Ch). Near‐infrared dye IR780 was encapsulated in cationic PMAD‐Ch micelles, which then were used to form IR780 micelleplexes with siRNA. The micelleplexes displayed improved gene silencing efficiency upon laser irradiation, which was attributed to enhanced endosomal escape because of the photothermal effects of the encapsulated IR780. The IR780 micelleplexes retained the CXCR4 antagonism and inhibition of cancer cell invasion of the parent PAMD. Overall, this study validates codelivery of IR780 in siRNA micelleplexes as promising photothermally controlled siRNA delivery approach. [ABSTRACT FROM AUTHOR]

IR780, a molecule with a strong optical absorption and emission in the near infrared (NIR) region, is receiving an increasing attention from researchers working in the area of cancer treatment and imaging. Upon irradiation with NIR light, IR780 can produce reactive oxygen species as well as increase the body temperature, thus being a promising agent for application in cancer photodynamic and photothermal therapy. However, IR780’s poor water solubility, fast clearance, acute toxicity and low tumor uptake may limit its use. To overcome such issues, several types of nanomaterials have been used to encapsulate and deliver IR780 to tumor cells. This mini-review is focused on the application of IR780 based nanostructures for cancer imaging, and photothermal, photodynamic and combinatorial therapies. [ABSTRACT FROM AUTHOR]

Stimuli-responsive polymeric nanoparticles are useful for overcoming challenges such as transfection efficiency and the specific and safe delivery of genes to cancer cells. Transfection outcomes can be improved through spatially and temporally controlled gene release. We formulated a nanoassembly comprising a disulfide-crosslinked polyethylenimine (ssPEI) conjugated with a tumor-specific cell-penetrating peptide (DS 4-3) (SPD) polyplex and bovine serum albumin (BSA)-loaded IR780 (BI) nanoparticle, thereby forming a dual-stimulus-triggered, tumor-penetrating and gene-carrying nanoassembly (BI-SPD) via electrostatic complexing. BI-SPD nanoassembly were composed of highly stable nanosized complexes with an average size of 457 ± 27.5 nm, exhibiting an up to two-fold enhanced transfection efficiency with no sign of potential cytotoxicity in breast cancer cells. Moreover, upon laser irradiation, a four-fold increase in transfection efficiency was achieved due to the rapid endosomal escape of polyplexes triggered by the local heat induced by the BI-SPD nanoassembly. Additionally, the high redox environment in tumor cells facilitated the disassembly of the SPD polyplex for efficient plasmid release in the cytosol. The BI-SPD nanoassembly also exhibited high penetration and enhanced photothermally triggered gene expression in the 4T1 spheroid model. This BI-SPD nanoassembly has the potential to enhance the expression of therapeutic genes in tumor models without causing significant toxicity to surrounding healthy tissues, since it has shown higher tumor targeting and accumulation in the 4T1 tumor in mice model. [ABSTRACT FROM AUTHOR]

[Display omitted] • An effective nanoparticle system for carrying IR780 and Idarubicin was designed to combine PTT/PDT and chemotherapy to treat NHL. • Upon near-infrared laser irradiation at 808 nm, PEG-b-PTMC nanoparticle showed strong PTT/PDT efficacy with high-efficiency endocytosis and increasing reactive oxygen species (ROS) generation. • IR780 + IDA NPs has been successfully delivered and exhibited significant synergistic effects on inhibiting cell proliferation in Raji and U937 cells. • IR780 + IDA NPs shows a significant therapeutic effect on lymphoma and has excellent biocompatibility and safety in vivo. A certain proportion of non-Hodgkin's lymphoma (NHL) patients will relapse after standard chemotherapy with an anthracycline-based regimen. Therefore, identifying novel therapeutic methods are a vital topic for improving therapeutic effects of NHL. IR780, a near-infrared dye, can be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed an effective nanoparticle system for carrying IR780 and Idarubicin, thus hoping to combine PTT/PDT and chemotherapy to treat NHL. This nanosystem consisted of PEG-b-PTMC nanoparticles. IR780 and Idarubicin (IDA) were loaded separately into PEG-b-PTMC nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PEG-b-PTMC nanoparticle (IR780 + IDA NPs) showed strong PTT/PDT efficacy with high-efficiency endocytosis and increasing reactive oxygen species (ROS) generation. By the evaluation of the photothermal conversion, we can confirm that IR780 + IDA NPs has been successfully delivered and exhibited significant synergistic effects on inhibiting cell proliferation in Raji and U937 cells. In vivo experiments have also demonstrated that IR780 + IDA NPs has a significant inhibitory effect on lymphoma and has a good biological safety. In summary, we put forward a therapeutic strategy for NHL treatment by combining PTT/PDT and chemotherapy. [ABSTRACT FROM AUTHOR]

The present study reports a drug delivery system comprising nanostructured lipid carrier (NLCs) within liposomes (Lip-NLCs). This multiple lipid carrier complex features laser-triggered responsive drug release. Both hydrophobic and hydrophilic drugs can be loaded into the same formulation by applying an all-in-one strategy. We hypothesized that if we loaded the hydrophobic near-infrared (NIR) dye IR780 into the liposome phospholipid bilayer, the bilayer would be disrupted by laser irradiation so that drug release would be triggered remotely at the tumor site. We used in vitro and in vivo methods to verify that laser irradiation facilitated controlled release of both hydrophobic and hydrophilic drugs. The degree of drug release triggered by NIR laser light could be adjusted by varying the laser intensity and irradiation time. Following laser treatment, hydrophilic AMD3100 was released from the aqueous liposome chamber and then bound with CXCR4 receptors on the tumor cell surface to inhibit metastasis. NLCs carrying lipophilic IR780 were also released from the aqueous chamber of liposomes and taken up into tumor cells to enhance the photothermal therapeutic effect of IR780. More importantly, Lip-NLCs loaded with IR780 and AMD3100 (IR780-AMD-Lip-NLCs) exhibited enhanced anti-tumor and anti-metastasis effects. These results suggest that Lip-NLCs are a safe and simply prepared all-in-one platform for delivery of drugs with different solubilities. This system facilitates easily controlled release of cargoes to achieve multi-functional combined therapy. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to use hemoglobin (Hb) nanoparticles (NPs) to improve oral bioavailability of a near-infrared dye IR780 for in vivo antitumor application in photothermal therapy. Methods: One-step acid-denaturing method was used to encapsulate IR780 into self-assembled Hb NPs (IR780@Hb NPs). Pharmacokinetics, biodistribution and antitumor effect were studied in vivo. Results: The Hb NPs showed high stability in enzymatic and acidic conditions similar to the gastric environment, and enhanced absorption of IR780 into the blood. In vivo imaging revealed that IR780 could accumulate at the tumor sites and effectively caused photothermal effect, which resulted in tumor ablation after oral administration in tumor-bearing mice. Conclusion: Hb NPs represent a promising delivery system for improving oral absorption of photosensitizer dyes, which could open new treatment modalities in cancer. [ABSTRACT FROM AUTHOR]

Cancer treatments that use a combination of approaches with the ability to affect multiple disease pathways have proven highly effective. The present study reports on CXCR4-targeted nanostructured lipid carriers (NLCs) with a CXCR4 antagonist AMD3100 in the shell (AMD-NLCs). AMD-NLCs loaded with IR780 (IR780-AMD-NLCs) reduced the invasiveness of cancer cells, while simultaneously mediating efficient tumor targeting and photothermal therapeutic outcomes. We present the combined effect of encapsulated IR780 on photothermal therapy and of the AMD3100 coating on tumor targeting, CXCR4 antagonism and inhibition of cancer cell invasion and breast cancer lung metastasis in vitro and in vivo . IR780-AMD-NLCs exhibited excellent IR780 loading capacity and AMD3100 coating efficiency. The photothermal properties of IR780 were improved by encapsulation in NLCs. The encapsulated IR780 displayed better heat generating efficiency than free IR780 when exposed to repeated laser irradiation. CXCR4 antagonism and cell invasion assays confirmed that IR780-AMD-NLCs fully inhibited CXCR4 while IR780-NLCs did not function as CXCR4 antagonists. AMD3100-coated NLCs accumulated at high levels in tumors, as judged by in vivo imaging and biodistribution assays. Furthermore, CXCR4-targeted NLCs exhibited an encouraging photothermal anti-tumor effect as well as anti-metastatic efficacy in vivo . These findings suggest that this simple and stable CXCR4-targeted IR780 delivery system holds great promise for prevention of metastasis and for photothermal treatment of tumors. Statement of Significance Breast cancer is a major threat to human health, it is not the primary breast tumor that is ultimately responsible for the majority of deaths, but the tumor metastasis, which frequently follows a specific pattern of dissemination. We report development of a novel dual-function nanostructured lipid carrier (NLC) for breast cancer treatment. The carrier encapsulates NIR dye IR780 in its core and contains antagonist of the chemokine receptor CXCR4 in its shell. Our results show that by combining the CXCR4 antagonism with photothermal effect of the dye leads to remarkable antitumor and antimetastatic activity in syngeneic orthotopic model of metastatic breast cancer. Furthermore, the developed system also shows a theranostic potential due to NIR fluorescence of the encapsulated dye. [ABSTRACT FROM AUTHOR]