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The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFβ pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF‐loaded nanoplatform (PEG@mPt‐HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti‐TGFβ effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt‐HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFβ pathway inhibition, which resulted in increased anti‐cancer efficacy. Importantly, the liver toxicity observed in HF‐treated mice was negligible in those treated by PEG@mPt‐HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment. [ABSTRACT FROM AUTHOR]

Abstract The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFβ pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF‐loaded nanoplatform (PEG@mPt‐HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti‐TGFβ effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt‐HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFβ pathway inhibition, which resulted in increased anti‐cancer efficacy. Importantly, the liver toxicity observed in HF‐treated mice was negligible in those treated by PEG@mPt‐HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment.

Abstract Backgrounds Microwave sensitization nanoplatform, integrating multiple functional units for improving tumor selectivity, is of great significance for clinical tumor microwave treatment. Lanthanide europium metal organic framework (EuMOF) is expected to be a theranostic nanoplatform owing to its unique luminescent and microwave sensitization properties. However, it is difficult to be applied to complicated biological systems for EuMOF due to its rapid degradation induced by the solvent molecular and ionic environment. In this work, a luminescent EuMOF nanocomposite (EuMOF@ZIF/AP-PEG, named EZAP) was designed, which brought the multifunctional characteristics of microwave sensitization, fluorescence imaging and drug loading. Results Lamellar EuMOF was synthesized by a hydrothermal method. Through the charge adsorption mechanism, the zeolite imidazole framework (ZIF) structure was intensively assembled on the surface of EuMOF to realize the protection. Then, through in-situ Apatinib drug loading and PEG modification, EZAP nanocomposite was finally obtained. Apatinib (AP) was a kind of chemotherapy drug approved by Food and Drug Administration for targeted therapy of tumors. PEG modification increased long-term circulation of EZAP nanocomposite. The physical and chemical structure and properties of EuMOF@ZIF (EZ) were systematically represented, indicating the successful synthesis of the nanocomposite. The toxic and side effects were negligible at a safe dose. The growth of human liver cancer cells and murine liver cancer cells in vitro was significantly inhibited, and the combined microwave-thermal therapy and chemotherapy in vivo achieved high anti-cancer efficacy. Moreover, EZAP nanocomposite possessed bright red fluorescence, which can be applied for tumor imaging in tumor-bearing mice in vivo. Conclusion Therefore, EZAP nanocomposite showed high microwave sensitization, excellent fluorescence properties and outstanding drug loading capacity, establishing a promising theranostic nanoplatform for tumor therapy and fluorescence imaging. This work proposes a unique strategy to design for the first time a multifunctional nanoplatform with lanthanide metal organic frameworks for biological applications in tumor therapy and diagnosis. Graphical Abstract

The theranostics of lymph node metastasis has always been one of the major obstacles to defeating breast cancer and an important decisive factor in the prognosis of patients. Herein, we design NaGdF4:Yb,Tm@NaLuF4 upconversion nanoparticles with PEG and anti-HER2 monoclonal antibody (trastuzumab, Herceptin) (NP-mAb), the delivery of NP-mAb through the lymphatic system allows for effective targeting and accumulation in lymphatic metastasis. Combination of radionuclides 68Ga and 177Lu could be chelated by the bisphosphate groups of NP-mAb. The obtained nanoprobe (NP-mAb) and nanonuclear drug (68Ga-NP-mAb or 177Lu-NP-mAb) exhibited excellent stability and show high accumulation and prolong retention in the lymph node metastasis after intratumoral injection into the foot pad by nearinfrared fluorescence (NIRF), single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. Utilizing the b-rays released by 177Lu, 177Lu-NP-mAb could not only decrease the incidence of lymph node metastasis, but also significantly decrease the volumes of lymph node metastasis. Additionally, 177Lu-NP-mAb induce no obvious toxicity to treated mice through blood routine, liver and kidney function assay. Therefore, nanoprobe and nanonuclear drug we designed could be acted as excellent theranostics agents for lymph node metastasis, providing potential alternatives diagnose and treatment option for lymph node metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: The biomedical application of metal–organic frameworks in cancer theranostics has become a research hotspot with rapid progress. As a typical representative, ZIF–8 attracts increasing interest from researchers due to its good performance and potential. In this review, we updated recent discoveries on the ZIF–8–based nanoplatforms for cancer, discussed the problems in current research and the obstacles for clinical translation of ZIF–8, and also proposed an outlook on its future development. Cancer severely threatens human health and has remained the leading cause of disease–related death for decades. With the rapid advancement of nanomedicine, nanoscale metal–organic frameworks are believed to be potentially applied in the treatment and biomedical imaging for various tumors. Zeolite imidazole framework (ZIF)–8 attracts increasing attention due to its high porosity, large specific surface area, and pH–responsiveness. The designs and modifications of ZIF–8 nanoparticles, as well as the strategy of drug loading, demand a multifaceted and comprehensive understanding of nanomaterial features and tumor characteristics. We searched for studies on ZIF–8–based nanoplatforms in tumor theranostics on Web of Science from 2015 to 2022, mainly focused on the research published in the past 3 years, summarized the progress of their applications in tumor imaging and treatment, and discussed the favorable aspects of ZIF–8 nanoparticles for tumor theranostics as well as the future opportunities and potential challenges. As a kind of metal–organic framework material full of potential, ZIF–8 can be expected to be combined with more therapeutic systems in the future and continue to contribute to all aspects of tumor therapy and diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC. Graphical Abstract

Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vulnerable plaques. Therefore, it is necessary to develop efficient strategies to improve the diagnosis accuracy and achieve visualized treatment of atherosclerosis. Herein, we establish an inflamed endothelium-targeted three-in-one nucleic acid nanogel system that can reverse the inflammatory state of endothelial cells (ECs) in plaques and simultaneously achieve real-time monitoring of the therapy process for efficient atherosclerosis diagnosis and treatment. For this purpose, contrast agent (Gd-DOTA) and VCAM-1-targeted peptide (VP) are first covalently conjugated onto DNA strands by click reaction respectively, which could self-assemble into Y-shaped structures (Gd-Y1 and VP-Y2 motifs) with magnetic resonance (MR) imaging and endothelium targeting capacities. Thereafter, NF-κB subunit p65-targeting siRNA (siNF-κB) is crosslinked with Gd-Y1 and VP-Y2 motifs to construct the endothelium-targeting nanogel platform. With contrast agents inside, the nanogel enables MR-based diagnosis and visualized therapy of atherosclerosis, providing accurate prognostic analysis and indications for treatment results, which ensures timely disclosure of insensitive individuals and avoids acute lethal events. By delivering siNF-κB to inflammatory endothelium, the nanogel significantly regresses plaques in both the aorta and carotid artery with reduced inflammation cytokines, collagens, macrophages, and apoptotic cells, providing a potential anti-inflammation strategy to treat atherosclerosis and avoid acute cardiovascular disease. With contrast agent, peptide, and siNF-κB inside, the as-prepared endothelium-targeted nucleic acid nanogel realizes MR imaging and real-time monitoring of anti-inflammation treatment of atherosclerosis. By targeted functionalizing in inflammatory endothelial cells, the NF-κB nanogel significantly alleviates inflammation and regresses plaques in atherosclerotic mice as characterized by MR imaging and pathological analysis, providing a promising theranostic anti-inflammation strategy for atherosclerosis. [Display omitted] • A facile and efficient nanoplatform with targeting, diagnosis, and therapy capacities. • High diagnosis accuracy and resolution by targeting lesional inflamed endothelium. • Reverse endothelium inflammation by inhibiting NF-κB protein in endothelial cells. • Real-time monitoring of spatial lesion information during atherosclerosis treatment. • Timely detection of insensitive individuals to reduce the incidence of fatal event. [ABSTRACT FROM AUTHOR]

Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe3+-incorporated ceria-based MSN nanoparticles possessing a higher Ce3+-to-Ce4+ ratio than those revealed by ceria-only nanoparticles. The as-prepared Fe/Ce-MSN nanoparticles exhibited an excellent efficiency in scavenging reactive oxygen species (ROS), which is attributed to improving the superoxide dismutase (SOD) mimetics activity by increasing Ce3+ content and maintaining a higher activity of catalase (CAT) mimetics via including ferrite ion in nanoparticles. The fast Fe/Ce-MSN biodegradation, which is sensitive to the mild acidic microenvironment of inflammation, can accelerate Fe/Ce ion release, and the freed Fe ions enhanced T2-weighted magnetic resonance imaging in the inflammation site. PEGylated Fe/Ce-MSN nanoparticles in vitro cell models significantly attenuated ROS-induced inflammation, oxidative stress, and apoptosis in macrophages by scavenging overproduced intracellular ROS. More importantly, Fe/Ce-MSN-PEG NPs exhibited significant anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels in vitro. Additionally, it can promote the macrophages polarization of pro-inflammatory M1 phenotype towards an anti-inflammatory M2 phenotype. Thus, the novel pH-responsive theranostic nanoplatform shows great promise for inflammation and oxidative stress-associated disease treatment.

A natural killer (NK)-92 cell membrane-camouflaged mesoporous MnO 2 -enveloped Au@Pd (Au@Pd@MnO 2) nanoparticles (denoted as APMN NPs)-based versatile biomimetic theranostic nanoplatform was developed for magnetic resonance (MR) imaging-guided multimodal synergistic antitumor treatments. In this core-shell nanostructure, an Au@Pd core induced near-infrared (NIR)-activatable hyperthermal effects and nanozyme catalytic activity, while a mesoporous MnO 2 shell not only afforded a high drug-loading capability, tumor microenvironment (TME)-triggered MR imaging and drug release, but also endowed catalase-, glutathione peroxidase-, and Fenton-like activities. Furthermore, the NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein-mediated tumoral uptake property. The doxorubicin-loaded APMN (D-APMN) NPs exhibited TME-responsive drug release properties. Furthermore, the cellular uptake, in vivo MR imaging, and NIR thermal imaging confirmed the active tumor-targeting capability and TME-responsive MR imaging property of these biomimetic NPs. An antitumor efficacy test, histological analyses, and blood biochemical profiles suggested that the developed D-APMN NPs possessed a high antitumor activity and biosafety in tumor-bearing nude mice. Therefore, the developed APMN NPs held great potential as an intelligent and comprehensive theranostic nanoplatform for tumor-specific bioimaging and TME-responsive multimodality treatment based on photothermal therapy, chemodynamic therapy, and chemotherapy. Exploring intelligent and comprehensive theranostic nanoplatforms to integrate tumor-specific bioimaging and TME-responsive multimodal therapy effectively is a challenge. Herein, we successfully developed a new kind of NK-92 cell membrane-camouflaged mesoporous MnO 2 -enveloped Au@Pd nanoparticles (APMN NPs)-based versatile biomimetic theranostic nanoplatform for the potential MR imaging-guided multimodal synergistic antitumor treatments. These NPs could integrate unique structural, optical, multiple-catalytic, paramagnetic, and biological merits of NK-92 cell membrane, Au@Pd cores and mesoporous MnO 2 shell in a single nanoplatform. The NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein–mediated tumoral uptake property. The new information obtained from this study may be beneficial to promote the development of novel TME-responsive versatile "Trojan horse" theranostic nanoplatforms for efficient MR imaging-guided multimodal synergistic treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Backgrounds: Microwave sensitization nanoplatform, integrating multiple functional units for improving tumor selectivity, is of great significance for clinical tumor microwave treatment. Lanthanide europium metal organic framework (EuMOF) is expected to be a theranostic nanoplatform owing to its unique luminescent and microwave sensitization properties. However, it is difficult to be applied to complicated biological systems for EuMOF due to its rapid degradation induced by the solvent molecular and ionic environment. In this work, a luminescent EuMOF nanocomposite (EuMOF@ZIF/AP-PEG, named EZAP) was designed, which brought the multifunctional characteristics of microwave sensitization, fluorescence imaging and drug loading. Results: Lamellar EuMOF was synthesized by a hydrothermal method. Through the charge adsorption mechanism, the zeolite imidazole framework (ZIF) structure was intensively assembled on the surface of EuMOF to realize the protection. Then, through in-situ Apatinib drug loading and PEG modification, EZAP nanocomposite was finally obtained. Apatinib (AP) was a kind of chemotherapy drug approved by Food and Drug Administration for targeted therapy of tumors. PEG modification increased long-term circulation of EZAP nanocomposite. The physical and chemical structure and properties of EuMOF@ZIF (EZ) were systematically represented, indicating the successful synthesis of the nanocomposite. The toxic and side effects were negligible at a safe dose. The growth of human liver cancer cells and murine liver cancer cells in vitro was significantly inhibited, and the combined microwave-thermal therapy and chemotherapy in vivo achieved high anti-cancer efficacy. Moreover, EZAP nanocomposite possessed bright red fluorescence, which can be applied for tumor imaging in tumor-bearing mice in vivo. Conclusion: Therefore, EZAP nanocomposite showed high microwave sensitization, excellent fluorescence properties and outstanding drug loading capacity, establishing a promising theranostic nanoplatform for tumor therapy and fluorescence imaging. This work proposes a unique strategy to design for the first time a multifunctional nanoplatform with lanthanide metal organic frameworks for biological applications in tumor therapy and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods: A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results: The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion: Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC. [ABSTRACT FROM AUTHOR]

Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single-site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO 2 (H–MnO 2)-based theranostic nanoplatform, DNAzyme@H–MnO 2 -MUC1 aptamer (DHMM), was constructed for the simultaneous multi-site diagnosis and multiple treatment of breast cancer. The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi-site fluorescence imaging-guided high-efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/GT) for breast cancer. The H–MnO 2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL μg−1) and FAM-DNAzyme (3.37 pmoL μg−1), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dual-channel fluorescence imaging at different sites. Moreover, the self-supplied Mn2+ was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high-efficient GT and stimulated the Fenton-like reaction for CDT. The H–MnO 2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi-site fluorescence imaging-guided synergistic treatment with an apoptosis rate of 71.82%. This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi-site fluorescence imaging-guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer treatment. [Display omitted] • DHMM realized multi-site imaging and highly efficient PTT/CDT/GT synergistic therapy with a final apoptosis rate of 71.82%. • The H–MnO 2 exhibits large loading capacity for FAM-DNAzyme (3.37 pmoL μg−1) and Cy5-MUC1 aptamer (3.05 pmoL μg−1). • The H–MnO 2 showcases excellent photothermal properties with a photothermal conversion efficiency of 44.16%. [ABSTRACT FROM AUTHOR]

Brain tumors mainly originate from glial cells and are classified as gliomas. Malignant gliomas represent an incurable disease; indeed, after surgery and chemotherapy, recurrence appears within a few months, and mortality has remained high in the last decades. This is mainly due to the heterogeneity of malignant gliomas, indicating that a single therapy is not effective for all patients. In this regard, the advent of theranostic nanomedicine, a combination of imaging and therapeutic agents, represents a strategic tool for the management of malignant brain tumors, allowing for the detection of therapies that are specific to the single patient and avoiding overdosing the non-responders. Here, recent theranostic nanomedicine approaches for glioma therapy are described.

Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer. Development and functionality of the GPC1-GEM-NPs. (A) The preparation of GPC1-GEM-NPs. (B) GPC1-GEM-NPs as tumor-targeted multifunctional theranostic nanoplatforms for multimodal imaging and therapy by GPC1-mediated antibody–antigen combination. ① Coincubation; ② Au–S coupling chemistry; ③ amidation reaction; ④ antibody–antigen combination; ⑤ endocytosis; ⑥ endosome escape; ⑦ pH/hyaluronidase response. [ABSTRACT FROM AUTHOR]

Graphical abstract AuNCs-HA exhibited PA imaging guided combined radiotherapy, PDT and PTT trimodalites, leading to effectively synergistic anticancer efficacy. Abstract In this work, we developed a novel multifunctional nanoplatform based on hyaluronic acid modified Au nanocages (AuNCs-HA). The rational design of AuNCs-HA renders the nanoplatform three functionalities: (1) AuNCs-HA with excellent LSPR peak in the NIR region act as contrast agent for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT); (2) the nanoplatform with high-energy rays (X-ray) absorption and auger electrons generation acts as a radiosensitizer for radiotherapy; (3) good photocatalytic property and large surface area make AuNCs-HA a photosensitive agent for photodynamic therapy (PDT). In vivo results demonstrated that AuNCs-HA presented excellent PA imaging performance after intravenous injection, which provided contour, size, and location information of the tumor. Moreover, because AuNCs-HA could combine radiotherapy and phototherapy together, the tumors treated with AuNCs-HA showed complete growth inhibition, comparing to that with each therapy alone. Taken together, our present study demonstrates that AuNCs-HA is of great potential as a multifunctional nanoplatform for PA imaging-guided radio- and photo-therapy of tumor. Statement of Significance In this study, a commendable theranostic nanoplatform based on hyaluronic acid modified AuNCs (AuNCs-HA) was developed. In our approach, the dilute solution of Gold(III) chloride is slowly dripped into Ag nanocubes solution, then the Au nanocages were obtained by redox reaction, and followed by HA modification. We explored them, simultaneously, as radiosensitizers for RT, photosensitizers for PDT, and therapeutic agents for PTT. Compared to that of each therapies alone, the combination of radio-therapy and photo-therapy results in a considerably improved tumor eliminating effect and efficiently inhibited tumor growth. In addition, AuNCs-HA exhibited remarkably strong PA signals for precise identification of the location, size, and boundary of the tumor, thereby facilitating imaging-guided therapy. In brief, our design of AuNCs-HA represents a general and versatile strategy for building up cancer-targeted nanotheranostics with desired synergistic imaging and therapy functionalities. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • CuS nanoparticles were synthesized using versatile polydopamine as bio-template. • Without additional surfactant, the nanocomposite shows favorable biocompatibility. • The integration of MRI and photothermal therapy enables more effective treatment. • The nanocomposite possesses high stability and excellent photothermal property. Abstract Copper sulfide nanoparticles(CuS NPs) have attracted considerable interest in the field of photothermal therapy(PTT) due to its low cost, easy preparation and favorable photothermal effect. However, lack of reliable visualization and relatively poor biocompatibility restrict its further bio-application. To overcome these limitations, polydopamine(PDA, a melanin-like biopolymer) stabilized CuS NPs and further chelated with iron ions (denoted as CuPDF) were designed as a versatile nanoplatform for T 1 -weighted MR imaging-guided PTT. In this system, PDA served as both bio-template to synthesis CuS NPs and an active platform to give MRI diagnostic capability. The as-prepared CuPDF NPs demonstrated strong absorption at NIR region, nearly three times higher than that of pure PDA NPs at 808 nm. Moreover, toxicity studies and histology evalution verified that CuPDF NPs possess excellent biocompatibility. In addition, CuPDF NPs showed significant MRI signal enhancement with high longitudinal relaxivity (r 1 = 4.59 mM−1 s−1). In vivo MRI and biodistribution test confirmed the efficient accumulation of CuPDF NPs in the tumor region. After intravenous injection of CuPDF, irreversible tumor ablation was successfully achieved without inducing any obvious side effects by using 808-nm laser irradiation. All in all, these results indicated that the developed CuPDF NPs hold great potential as an effective theranostic agent for MR imaging guided PTT in vivo. [ABSTRACT FROM AUTHOR]

We report herein the development of a smart magnetic nanoparticle-aptamer probe, or theranostic nanoprobe, which can be used for targeted imaging and as a drug carrier for hepatocellular carcinoma treatment. The theranostic nanoprobe combines the delivery potential of a non-toxic cellulose derivative polymer, specific capability of cancer-specific molecule (DNA-based EpCAM aptamer) and the imaging capability of magnetic iron oxide nanoparticles. Our proof-of-concept design demonstrates efficient in vitro MR imaging of the cancer cells, and enhanced delivery of an anticancer drug into the cancer cells with comparable treatment efficacy. [ABSTRACT FROM AUTHOR]

Abstract: Recently, nanomaterials with multiple functions, such as drug carrier, MRI and optical imaging, photothermal therapy etc, have become more and more popular in the domain of cancer research. In this study, a C60–IONP nanocomposite is synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60) and then functionalized by polyethylene glycol (PEG2000), giving C60–IONP–PEG with excellent stability in physiological solutions, finally folic acid (FA), a widely used tumor targeting molecule, was linked to C60–IONP–PEG in order to obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in mice models. Herein, a hybrid nanoplatform with multi-functional characteristics for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal therapy (RTT) and magnetic targeting applications was developed and explored its biofunctions in vitro and in vivo. C60–IONP–PEG–FA showed neglectable toxicity, not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agent, but also as a strong photosensitizer and powerful agent for photothermal ablation of tumor, furthermore a remarkable synergistic enhancement of PDT combination with RTT was also observed during the treatment both in vitro and in vivo. Moreover, the multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent active tumor targeting and magnetic targeted abilities. This work showed the multi-functional C60–IONP–PEG–FA nanoplatform had a great potential for cancer theranostic applications. [Copyright &y& Elsevier]

Bloodstream infection with methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant bacteria kill several million people in the world every year. Detection of drug-resistant bacteria in the blood stream is clinically important to save lives. Driven by this need, multifunctional theranostic nanoplatforms have been developed for simultaneous targeted imaging and multimodal photodestruction of MRSA in a whole-blood sample. Experimental data for the whole-blood sample spiked with MRSA show that the theranostic nanoplatform can be used for fluorescence imaging after magnetic separation even in a 10−5:1 ratio. A targeted photodynamic and photothermal combined treatment shows that the multimodal treatment regime can dramatically enhance the possibility of destroying MRSA in vitro. Therefore, our developed theranostic nanoplatform have a great potential as a fluorescent marker and as a light absorber for combined therapy in clinical settings. The possible mechanisms and operating principles are discussed for targeted imaging and combined therapeutic actions using theranostic nanoplatform. [ABSTRACT FROM AUTHOR]

The theranostics of lymph node metastasis has always been one of the major obstacles to defeating breast cancer and an important decisive factor in the prognosis of patients. Herein, we design NaGdF 4 :Yb,Tm@NaLuF 4 upconversion nanoparticles with PEG and anti-HER2 monoclonal antibody (trastuzumab, Herceptin) (NP-mAb), the delivery of NP-mAb through the lymphatic system allows for effective targeting and accumulation in lymphatic metastasis. Combination of radionuclides 68 Ga and 177 Lu could be chelated by the bisphosphate groups of NP-mAb. The obtained nanoprobe (NP-mAb) and nanonuclear drug ( 68 Ga-NP-mAb or 177 Lu-NP-mAb) exhibited excellent stability and show high accumulation and prolong retention in the lymph node metastasis after intratumoral injection into the foot pad by near-infrared fluorescence (NIRF), single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. Utilizing the β-rays released by 177 Lu, 177 Lu-NP-mAb could not only decrease the incidence of lymph node metastasis, but also significantly decrease the volumes of lymph node metastasis. Additionally, 177 Lu-NP-mAb induce no obvious toxicity to treated mice through blood routine, liver and kidney function assay. Therefore, nanoprobe and nanonuclear drug we designed could be acted as excellent theranostics agents for lymph node metastasis, providing potential alternatives diagnose and treatment option for lymph node metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Liang, Shi, Jun, Fan, Yang, Wang, Li and Zhu.)

The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFβ pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF-loaded nanoplatform (PEG@mPt-HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti-TGFβ effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt-HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFβ pathway inhibition, which resulted in increased anti-cancer efficacy. Importantly, the liver toxicity observed in HF-treated mice was negligible in those treated by PEG@mPt-HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment., Competing Interests: The authors declare no competing financial or non‐financial interests., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe 3+ -incorporated ceria-based MSN nanoparticles possessing a higher Ce 3+ -to-Ce 4+ ratio than those revealed by ceria-only nanoparticles. The as-prepared Fe/Ce-MSN nanoparticles exhibited an excellent efficiency in scavenging reactive oxygen species (ROS), which is attributed to improving the superoxide dismutase (SOD) mimetics activity by increasing Ce 3+ content and maintaining a higher activity of catalase (CAT) mimetics via including ferrite ion in nanoparticles. The fast Fe/Ce-MSN biodegradation, which is sensitive to the mild acidic microenvironment of inflammation, can accelerate Fe/Ce ion release, and the freed Fe ions enhanced T 2 -weighted magnetic resonance imaging in the inflammation site. PEGylated Fe/Ce-MSN nanoparticles in vitro cell models significantly attenuated ROS-induced inflammation, oxidative stress, and apoptosis in macrophages by scavenging overproduced intracellular ROS. More importantly, Fe/Ce-MSN-PEG NPs exhibited significant anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels in vitro . Additionally, it can promote the macrophages polarization of pro-inflammatory M1 phenotype towards an anti-inflammatory M2 phenotype. Thus, the novel pH-responsive theranostic nanoplatform shows great promise for inflammation and oxidative stress-associated disease treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dou, Zhang, Lin, Han, Wang, Wu, Zheng, Lu, Tang and He.)

Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform with enhanced therapeutic effects and reduced side effects to normal tissues attracts increasing attention. Herein, we developed a multifunctional theranostic nanoplatform using poly(lactic-co-glycolic acid) (PLGA) loaded with near-infrared (NIR) photothermal agent (new indocyanine green IR820), fluorescence imaging agent (ZnCdSe/ZnS quantum dots, QDs) and autophagy inhibitor (chloroquine, CQ). These PLGA/IR820/Fluorescence imaging agent/CQ co-loading nanoparticles (termed PIFC NPs) displayed photothermal effects, enhanced the stability of IR820 in vivo, and enabled QDs to have stable fluorescent signals in vitro and in vivo. The PIFC NPs with particle size around 240 nm aggregated to tumor sites through the high permeability and retention effects of solid tumors. The intracellular delivery of CQ molecules through PIFC NPs significantly attenuated the degradation of autophagic lysosomes in tumor cells and effectively inhibited the autophagy mediated repair of photothermal damaged cells. Under milder NIR irradiation conditions, PIFC NPs exhibited high antitumor effect. By regulating autophagy, PTT can be effectively sensitized, which will provide a new idea for future cancer treatment research., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Advance of nanomaterials and nanotechnology has offered new possibilities for photodynamic therapy (PDT). Large amount of different kinds of sensitizers and targeting moieties can now be loaded in nanometer's volume, which not only results in the improvement of the efficacy of PDT, but also enables the control of image-guided PDT with unprecedented precision and variation. This chapter shall overview the recently most studied inorganic nanomaterials for PDT., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window exhibits enhanced deep-tissue imaging capability. Likely, cancer therapy in the NIR-II window could provide deeper penetration depth and higher exposure to laser over NIR-I. However, the traditional application of excitation light is still in the NIR-I window. In view of the excellent imaging and therapeutic capabilities of NIR-II window, we have demonstrated a simple polyoxometalate (POM) clusters (molecular formula: (Na) n (PMo 12 O 40) or (NH 4 +) n (PMo 12 O 40)), which integrates NIR-II photoacoustic imaging and NIR-II photothermal therapy into an "all-in-one" theranostic nanoplatform, and could be used for PA imaging-guided photothermal therapy in the NIR-II window. In vivo experiments demonstrate that the POM clusters with good water solubility and biocompatibility were effective to kill tumor without recurrence and metastasis under 1064 nm laser illumination. The simple polyoxometalate (POM) clusters displayed excellent second near-infrared (NIR-II) absorption, which optimized photoacoustic imaging and photothermal treatment effect in the NIR-II window. Therefore, the POM clusters will be a promising candidate for cancer diagnosis and treatment in biomedicine and clinical application. Unlabelled Image • The polyoxometalate (POM) showed broad absorption in second near-infrared window. • The POM displayed good dispersion and biocompatibility. • The POM exhibited excellent photoacoustic imaging in NIR-II window. • Tumor could be effectively killed under 1064 nm laser illumination. • The simple clusters could accomplish integration of diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Application of 1064 nm activatable NIR-IIa fluorescence imaging (FI) and NIR-II photothermal therapy (PTT) results in high-resolution imaging and good deep-tissue therapy, respectively. Combining NIR-IIa FI with NIR-II PTT may allow precise diagnosis guided efficient treatment of deep-tissue tumors. However, designing a 1064 activatable theranostic nanoplatform using a single dye for both NIR-IIa FI and NIR-II PTT is a challenge. Herein, we synthesized squaraine-based semiconducting polymer nanoparticles (PSQPNs-DBCO) that were excited by a 1064 nm laser for precise NIR-IIa fluorescence imaging guided NIR-II PTT treatment. Combined with bioorthogonal labeling technology, the PSQPNs-DBCO largely accumulated in the tumor section, extremely enhancing signal-to-background ratio (SBR) of imaging and NIR-II PTT efficiency of tumor in live colorectal-bearing animals. Image 1 [ABSTRACT FROM AUTHOR]

• Hollow structure was used to increase the active sites for chemodynamic therapy. • Hollow Cu 9 S 8 nanoparticles exhibit better chemodynamic performance than solid one. • Combination of increased active sites and photothermal effect to enhance therapy. • Hollow Cu 9 S 8 is a low cost "all in one" nanoplatform for theranostics. A theranostic nanoplatform, combined with tumor imaging and therapy, especially a highly reactive multimodal synergistic treatment, can effectively improve the efficacy of treatment and reduce costs. Copper sulfide can be used as a theranostic nanoplatform due to its strong photoacoustic, photothermal, and Fenton-like catalytic performance. However, its Fenton-like catalytic performance is limited by the availability of surface reaction sites. A hollow Cu 9 S 8 theranostic nanoplatform, with photoacoustic imaging and enhanced chemodynamic performance based on the combination of an increased number of active sites and photothermal performance was constructed in this study. The specific area of the hollow Cu 9 S 8 nanoparticles was 1.7 times greater than that of solid Cu 9 S 8 nanoparticle, which greatly increased the number of active sites where catalysis could occur in the Fenton reaction, thereby improving the chemodynamic therapy performance. In addition, the excellent photothermal properties of the Cu 9 S 8 nanoparticles accelerated the generation of hydroxyl radicals (OH), which also enhanced the chemodynamic therapy performance. More importantly, the in vivo experiment demonstrated that the hollow Cu 9 S 8 theranostic nanoplatform exhibit good tumor photoacoustic imaging and enhanced chemodynamic therapy due to the combination of the increase in number of active sites and photothermal performance. Therefore, this work not only provides an excellent theranostic nanoplatform for tumor treatment, but also a new strategy for developing high performance chemodynamic agents. [ABSTRACT FROM AUTHOR]

Development of unique theranostic nanoplatforms for tumor imaging and therapy remains an active topic in current nanomedicine. Here, we designed a novel targeted theranostic nanoplatform for enhanced T 1 -weighted magnetic resonance (MR) imaging-guided chemotherapy by constructing layered double hydroxide (LDH)-stabilized ultrasmall iron oxide (Fe 3 O 4 ) nanoparticles with hyaluronic acid (HA) modified as targeting agents, and anticancer drug doxorubicin (DOX) loaded with a high loading efficiency. Methods : The structure and release property of LDH-Fe 3 O 4 -HA/DOX nanoplatforms were characterized systematically. B16 melanoma cells with CD44 receptors overexpressed were used as model cells to determine the biocompatibility, targeting capability, and therapeutic efficiency of nanoplatforms. For in vivo experiment, hyaluronidase (HAase) pretreatment was combined with nanoplatform administration to investigate the MR imaging and chemotherapeutic effect. Results : The LDH-Fe 3 O 4 -HA nanohybrids possess good colloidal stability and cytocompatibility, display an r 1 relaxivity 10-fold higher than the pristine ultrasmall Fe 3 O 4 (4.38 mM -1 s -1 vs 0.42 mM -1 s -1 ), and could release drug in a pH-responsive manner. In vitro experiments demonstrate that LDH-Fe 3 O 4 -HA/DOX nanohybrids are able to specifically target B16 cells overexpressing CD44 receptors and effectively release DOX to nucleus. In vivo results show that with the pretreatment of tumor tissue by HAase to degrade the overexpressed HA in extra-cellular matrix, the designed nanoplatforms have a better tumor penetration for significantly enhanced MR imaging of tumors and tumor chemotherapy with low side effects. Conclusion : The designed LDH-Fe 3 -HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced 4 -HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced T 1 -weighted MR imaging-guided chemotherapy of CD44 receptor-overexpressing tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The strategy of co-loading therapeutic agents in a single nanocarrier is the most common method in theranostic cancer research. However, it is still challenging to encapsulate theranostic agents that have different physicochemical properties in a single nanocarrier system because of the immiscibility between the hydrophobic fluorescent molecule and the hydrophilic drug molecule. Thus, we report a novel concept of a theranostic nanoparticle (NP) consisting of an amphiphilic near-infrared (NIR) dye as a hydrophilic drug delivery carrier with enhanced NIR imaging capability. Unlike conventional nanocarrier systems, the newly designed amphiphilic NIR dyes (Cy-C dyes) function as both the drug delivery carrier and the fluorescent imaging agent. It can be utilized for therapy and diagnosis simultaneously by simply encapsulating the hydrophilic drug. This method is innovative not only due to formation of the theranostic nanoparticle for immiscible hydrophilic drug delivery but also because of generation of strong fluorescence signals due to the Cy-C dyes on the surfaces of the NPs. In this study, Cy-C (C = C3, C6, and C9) dyes were designed by conjugating the heptamethine cyanine dye with poly(ethylene glycol) (PEG 5K ) and polyethyleneimine 2000 (PEI 2K ). The result was self-assembled structures that effectively encapsulated a hydrophilic drug molecule (MTX) without self-quenching and scattered light interference. Among the Cy-C NPs encapsulating MTX (Cy-C/MTX NPs), Cy-C6/MTX and Cy-C9/MTX formed a concentric supramolecular bilayer (like liposomes in aqueous solution) and were capable of translocating hydrophilic drug molecules to their aqueous interior spaces. The supramolecular bilayer structure of Cy-C9/MTX provides better particle stability and drug delivery efficacy than does the supramolecular monolayer structure of Cy-C3/MTX. In addition, Cy-C9/MTX demonstrated excellent blood circulation and long-term tumor retention qualities in living mice. The effective tumor suppression ability of Cy-C9/MTX validated the concept that the amphiphilic Cy-C9 dye is the best nanoplatform for theranostics based on hydrophilic drug delivery.

Brain tumors mainly originate from glial cells and are classified as gliomas. Malignant gliomas represent an incurable disease; indeed, after surgery and chemotherapy, recurrence appears within a few months, and mortality has remained high in the last decades. This is mainly due to the heterogeneity of malignant gliomas, indicating that a single therapy is not effective for all patients. In this regard, the advent of theranostic nanomedicine, a combination of imaging and therapeutic agents, represents a strategic tool for the management of malignant brain tumors, allowing for the detection of therapies that are specific to the single patient and avoiding overdosing the non-responders. Here, recent theranostic nanomedicine approaches for glioma therapy are described., (Copyright © 2019 d'Angelo, Castelli, Benedetti, Antonosante, Catanesi, Dominguez-Benot, Pitari, Ippoliti and Cimini.)

Integrating multimodality bioimaging and multiple stimuli-responsive controlled drug release properties into one single nanosystem for therapeutic application is highly desirable but still remains a challenge. Herein, we coated a hollow mesoporous silica shell on to upconversion nanoparticles (UCNPs) and conjugated pillarene-based supramolecular valves on to surface of UCNPs@hm-SiO 2 using amine-coumarin phototriggers to obtain the multifunctional nanoparticles, UCNPs@hm-SiO 2 -Cou-Cys-DOX/WP[5]. Benefiting from the core-shell structured UCNPs, the UCNPs@hm-SiO 2 -Cou-Cys-DOX/WP[5] can serve as efficient contrast agents for upconversion luminescence and T 1 -weighted magnetic resonance imaging in vitro/in vivo. More importantly, depending on exquisitely designed supramolecular valves, UCNPs@hm-SiO 2 -Cou-Cys-DOX/WP[5] can realize zero-premature release under normal physiological conditions (pH 7.4), which produces minimal damage to normal tissue, whereas this nanosystem can respond to several disease-related signals, including acid (most cancers), alkali (metabolic alkalosis), and Zn 2+ (Alzheimer's disease), along with two external stimuli, including near-infrared (NIR) light and reductive electrical potential, via altering the spatial structure of pseudorotaxanes, disassembling the molecular stalks, or undergoing photochemical reactions, ultimately resulting in opening of the gatekeepers and release of encapsulated drugs. The multifunctional UCNP-based nanoparticles were endowed with such quintuple stimuli-responsive controlled release characteristics. Specifically, in anticancer application, the rational utilization of the two of them, acid and NIR light, could regulate the release amount and rate of DOX from UCNPs@hm-SiO 2 -Cou-Cys-DOX/WP[5], accelerate the accumulation of DOX in cell nuclei, and thereby promote the cancer cell apoptosis, indicating that the nanomaterials have promising application in cancer treatment. This study provides a novel design strategy for constructing multifunctional UCNP-based nanoparticles with multiple stimuli-responsive drug release features, which have great potential in diagnosis and therapy of relevant diseases as theranostic nanomedicines.

Developments in technology such as theranostic nanoplatforms, which combine complementary imaging modalities and synergistic therapies, have brought new hope to the diagnosis and treatment of cancer, one of the most deadly diseases. In this article, a nanoplatform (AuNCs/PPI-ICG nanohybrid) with a theranostic effect was prepared using indocyanine green (ICG), a cyanine dye with bright near-infrared fluorescence (NIRF) and excellent photodynamic and photothermal performance, and it was loaded onto gold nanoclusters/pea protein isolate hybrid nanoparticles (AuNCs/PPI NPs). There was a linear relationship between ICG loading ratio and the concentration, within a concentration range of 0-5 mg/mL, making it possible to precisely control the concentration of loaded ICG. In addition, the AuNCs/PPI-ICG nanohybrid displayed outstanding loading stability and enhanced the aqueous stability of ICG, owing to the protectivity of AuNCs/PPI NPs. In vitro cell experiments showed that this biocompatible nanohybrid could be taken up by A549 cells and used as a fluorescent bioimaging probe. Moreover, because of Au, AuNCs/PPI NPs could also act as a potential computed tomographic (CT) contrast agent, and so the AuNCs/PPI-ICG nanohybrid had the potential to function as a dual-modal imaging agent. Finally, the as-prepared hybrid, with excellent photodynamic properties and exceptional photothermal capabilities, showed a satisfactory therapeutic effect in ablating A549 cancer cells. These results convincingly demonstrate that the AuNCs/PPI-ICG nanohybrid is a promising theranostic nanoplatform for NIRF/CT dual-modal imaging and for synergistic photodynamic therapy/photothermal therapy (PDT/PTT).

The optical imaging guided tumor vessels and vascular malformation visualization by using the second near infrared emission beyond 1500 nm (NIR-II) is emerged as the next generation fluorescence imaging technique for early tumor diagnosis and identification of tumor-associated vascular features. On the other hand, developing theranostic probes for NIR-II imaging guided photothermal therapy (PTT) is of great significance, which is rarely explored. Herein, a high performance theranostic nanoplatform based on the core-shell structured NaLuF 4 nanorods@polydopamine (denoted as NRs@PDA) by integrating the new advanced NIR-II imaging beyond 1500 nm with PTT function was developed for tumor-associated vascular malformation visualization and imaging-guided PTT. Methods : In this work, the hydrophilic NaLuF 4 NRs@PDA therapeutic probe was synthesized by using a reverse microemulsion method. The crystal phase, morphology, emission spectra and photothermal performance of the synthesized samples were systematically characterized. The NIR-II optical imaging and photothermal properties were investigated by in vitro and in vivo experiments. Results : The NaLuF 4 NRs@PDA therapeutic probe possessed efficient NIR-II emission centered at 1525 nm with high quantum yield (QY), good photo-stability and high biocompatibility. In vivo NIR-IIb imaging based on the designed probe can clearly visualize the whole-body vessel and brain vessel with high spatial resolution, especially tumor-associated vessels. In addition, in vitro and in vivo experiments also demonstrated that the designed NaLuF 4 NRs@PDA probe possessed efficient photothermal conversion efficiency (40.18%) for PTT ablation of tumor. Conclusion : With the excellent NIR-II imaging ability and PTT of tumor, the designed theranostic nanoplatform successfully realize the simultaneous tumor vessel diagnosis and tumor therapy, which may provide the opportunity of designing new theranostic bioprobes with combination of the NIR-II optical imaging technique and PTT function for tumor diagnosis and therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Herein, a novel multifunctional nanoplatform was designed toward multimodality imaging and photothermal therapy (PTT). It was found that Bi nanoparticles could grow in situ on the surface of NaYF 4 :20%Yb,2%Er@NaYF 4 :40%Yb@NaGdF 4 core-shell nanoparticles (labeled as UCNPs). In this structure, UCNPs were mainly employed as an upconversion luminescence (UCL) imaging agent, whereas the Bi nanoparticles worked as an effective CT imaging and photothermal agent. Importantly, a dense SiO 2 shell was employed to protect the Bi nanoparticles from oxidation, and it also endowed the nanoplatform with excellent hydrophilic ability. The effective UCL/CT imaging and PTT performances were emphasized by a series of in vivo experiments, which suggest that the integrated nanoplatform with imaging and therapy functions shows great promise in the biomedical field.

The combination of chemotherapy and photothermal therapy has aroused great interest due to its better antitumor effect than either single therapy alone. Herein, we report on the development of hydroxypropyl-β-cyclodextrin functionalized Fe 3 O 4 /carbon nanoparticles (HFCNPs) for pH/near-infrared (NIR) responsive drug release, magnetic resonance/NIR fluorescence (MR/NIRFL) imaging-guided combined chemo/photothermal therapy. The high doxorubicin (DOX) loading capacity (61.2%) and controlled drug release by NIR irradiation and weak acid microenvironment render HFCNPs a good vector for DOX delivery and controlled release. Moreover, the MR/NIRFL dual-modal imaging was used to define the tumor location, size, and boundary and to track the tumor accumulation of HFCNPs and their biodistribution. The efficient accumulation and prolonged retention time of the nanoparticles in tumor are beneficial to tumor therapy. Taking advantage of the NIR laser-induced heating and hence promoted drug permeation, remarkable tumor inhibition was realized by synergetic chemo/photothermal therapy. In conclusion, the current work offers a promising approach to the development of smart and efficient multimodal cancer-targeted nanotheranostics.

Theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, most photothermal agents are limited by their instability and low photothermal conversion efficiency. In this study, we report new conjugated polymer dots (Pdots) as multifunctional agents for photoacoustic (PA) imaging-guided PTT. The novel 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene-6,6'-dibromo-N,N'-(2-ethylhexyl)isoindigo (BDT-IID) Pdots are readily fabricated though nanoreprecipitation and can absorb strongly in the 650-700 nm region. Furthermore, the BDT-IID Pdots possess a stable nanostructure and an extremely low biotoxicity. In particular, its photothermal conversion efficiency can be up to 45%. More importantly, our in vivo results exhibit that the BDT-IID Pdots are able to offer concurrently enhanced PA contrast and sufficient photothermal effect. Consequently, the BDT-IID Pdots can be exploited as a unique theranostic nanoplatform for PA imaging-guided PTT of tumors, holding great promise for their clinical translational development.

Malignant tumor incidences have been rapidly rising recently and are becoming a serious threat to human health. Herein, a multifunctional cancer targeted theranostic nanoplatform is developed by in situ growth of iron oxide magnetic nanoparticles on carbon nanoparticles, and then loaded with fluorescent dye indocyanine green (ICG@MCNPs). The loading of ICG on the nanoplatform significantly improves its photostability, and hence facilitates long-term near-infrared fluorescence (NIRF) imaging and efficient photothermal therapy (PTT) of tumor. The in vivo NIRF imaging reveals that ICG@MCNPs can be targeted to the tumor site. Moreover, in vivo magnetic resonance imaging also confirmed the efficient accumulation of ICG@MCNPs in the tumor site. Inspiringly, the subsequent PTT of tumor-bearing mice is achieved, as evidenced by the complete ablation of the tumor and the recovery of the physiological indexes to normal levels. Benefitting from its low-cost, simple preparation, and excellent dual-modal imaging and therapy, the ICG@MCNPs-based theranostic nanoplatform holds great promise in tumor-targeted nanomedicine.

Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.

Paresh C. Ray and co‐workers report on page 357 the development of multifunctional theranostic nanoplatforms, which is capable of targeted detection and destruction of methicillin‐resistant Staphylococcus aureus (MRSA) from whole blood. The image shows that the theranostic nanoplatform has a great potential for simultaneous separation, imaging and multimodal photodestruction of MRSA in the blood sample. [ABSTRACT FROM AUTHOR]