Nanoassemblies of heptamethine cyanine dye-initiated poly(amino acid) enhance ROS generation for effective antitumour phototherapy.

Phototherapy shows great potential for pinpoint tumour treatment. Heptamethine cyanine dyes like IR783 have high potential as agents for antitumour phototherapy due to their inherent tumour targeting ability, though their effectiveness in vivo is unsatisfactory for clinical translation. To overcome this limitation, we present an innovative strategy involving IR783-based polymeric nanoassemblies that improve the dye's performance as an antitumoural photosensitizer. In the formulation, IR783 is modified with cysteamine and used to initiate the ring-opening polymerization (ROP) of the N-carboxyanhydride of benzyl-L-aspartate (BLA), resulting in IR783-installed poly(BLA). Compared to free IR783, the IR783 dye in the polymer adopts a twisted molecular conformation and tuned electron orbital distribution, remarkably enhancing its optical properties. In aqueous environments, the polymers spontaneously assemble into nanostructures with 60 nm diameter, showcasing surface-exposed IR783 dyes that function as ligands for cancer cell and mitochondria targeting. Moreover, the nanoassemblies stabilized the dyes and enhanced the generation of reactive oxygen species (ROS) upon laser irradiation. Thus, in murine tumor models, a single injection of the nanoassemblies with laser irradiation significantly inhibits tumour growth with no detectable off-target toxicity. These findings highlight the potential for improving the performance of heptamethine cyanine dyes in antitumor phototherapy through nano-enabled strategies.

Covalent RGD-graphene-phthalocyanine nanocomposite for fluorescence imaging-guided dual active/passive tumor-targeted combinatorial phototherapy.

Poor tumor selectivity, low stability and quenched fluorescence are the main challenges to be overcome for nanomedicine, and are mainly caused by the dissociation of the nanostructure and aggregation of chromophores in the biological environment. Herein, covalently connected nanoparticles RGD-graphene-phthalocyanine (RGD-GO-SiPc) were constructed based on RGD peptide, silicon phthalocyanine (SiPc) and graphene oxide (GO) via a conjugation reaction for fluorescence imaging-guided cancer-targeted combinatorial phototherapy. The prepared RGD-GO-SiPc exhibited supreme biological stability, high-contrast fluorescence imaging, significantly enhanced NIR absorption, high photothermal conversion efficiency (25.6%), greatly improved cancer-targeting capability, and synergistic photodynamic (PDT) and photothermal therapy (PTT) efficacy along with low toxicity. Both in vitro and in vivo biological studies showed that RGD-GO-SiPc is a kind of promising multifunctional nanomedicine for fluorescence imaging-guided combined photothermal and photodynamic therapy with dual active/passive tumor-targeting properties.

PLGA-collagen-BPNS Bifunctional composite mesh for photothermal therapy of melanoma and skin tissue engineering.

The treatment of melanoma requires not only the elimination of skin cancer cells but also skin regeneration to heal defects. To achieve this goal, a bifunctional composite scaffold of poly(DL-lactic-co-glycolic acid) (PLGA), collagen and black phosphorus nanosheets (BPNSs) was prepared by hybridizing a BPNS-embedded collagen sponge with a PLGA knitted mesh. The composite mesh increased the temperature under near-infrared laser irradiation. The incorporation of BPNSs provided the PLGA-collagen-BPNS composite mesh with excellent photothermal properties for the photothermal ablation of melanoma cells both in vitro and in vivo. The PLGA-collagen-BPNS composite mesh had high mechanical strength for easy handling. The PLGA-collagen-BPNS composite mesh facilitated the proliferation of fibroblasts, promoted the expression of angiogenesis-related genes and the genes of components of the extracellular matrix for skin tissue regeneration. The high mechanical strength, photothermal ablation capability and skin tissue regeneration effects demonstrate that the bifunctional PLGA-collagen-BPNS composite mesh is a versatile and effective platform for the treatment of melanoma and the regeneration of skin defects.

A Tumor-Targeting Near-Infrared Heptamethine Cyanine Photosensitizer with Twisted Molecular Structure for Enhanced Imaging-Guided Cancer Phototherapy.

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.

Plasmonic nanorod array for effective photothermal therapy in hyperthermia.

Optical properties of anisotropic gold nanorod arrays inside anodic aluminium oxide substrates enhance the longitudinal absorption intensities and the hyperthermia cancer cell killing at 42.1 °C under photothermal laser exposures at 671 nm.

Site-Selective Photosynthesis of Ag-AgCl@Au Nanomushrooms for NIR-II Light-Driven O2- and O2•--Evolving Synergistic Photothermal Therapy against Deep Hypoxic Tumors.

Light-driven endogenous water oxidation has been considered as an attractive and desirable way to obtain O2 and reactive oxygen species (ROS) in the hypoxic tumor microenvironment. However, the use of a second near-infrared (NIR-II) light to achieve endogenous H2O oxidation to alleviate tumor hypoxia and realize deep hypoxic tumor phototherapy is still a challenge. Herein, novel plasmonic Ag-AgCl@Au core-shell nanomushrooms (NMs) were synthesized by the selective photodeposition of plasmonic Au at the bulge sites of the Ag-AgCl nanocubes (NCs) under visible light irradiation. Upon NIR-II light irradiation, the resulting Ag-AgCl@Au NMs could oxidize endogenous H2O to produce O2 to alleviate tumor hypoxia. Almost synchronously, O2 could react with electrons on the conduction band of the AgCl core to generate superoxide radicals (O2•-)for photodynamic therapy. Moreover, Ag-AgCl@Au NMs with an excellent photothermal performance could further promote the phototherapy effect. In vitro and in vivo experimental results show that the resulting Ag-AgCl@Au NMs could significantly improve tumor hypoxia and enhance phototherapy against a hypoxic tumor. The present study provides a new strategy to design H2O-activatable, O2- and ROS-evolving NIR II light-response nanoagents for the highly efficient and synergistic treatment of deep O2-deprived tumor tissue.

A Versatile Nanoplatform for Broad-Spectrum Immunotherapy by Reversing the Tumor Microenvironment.

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.

Rationally designed upconversion nanoparticles for NIR light-controlled lysosomal escape and nucleus-based photodynamic therapy.

Cell nucleus-based photodynamic therapy is a highly effective method for cancer therapy, but it is still challenging to design nucleus-targeting photosensitizers. Here, we propose the "one treatment, multiple irradiations" strategy to achieve nucleus-based photodynamic therapy using the photosensitizer rose bengal (RB)-loaded and mesoporous silica-coated upconversion nanoparticles with the surface modification of amine group (UCNP/RB@mSiO2-NH2 NPs). After implementation into cancer cells, the rationally designed UCNP/RB@mSiO2-NH2 NPs could be specifically accumulated in the acidic lysosomes due to their amino group-decorated surface. Upon a short-term (3 min) irradiation of 980 nm near-infrared light, the reactive oxygen species produced by RB through the Förster resonance energy transfer between the upconversion nanoparticles and RB molecules could effectively destroy lysosomes, followed by the release of the UCNP/RB@mSiO2-NH2 NPs from the lysosomes. Subsequently, these released UCNP/RB@mSiO2-NH2 NPs could be transferred into the cell nucleus, where a second 980 nm light irradiation was conducted to achieve the nucleus-based photodynamic therapy. The rationally designed UCNP/RB@mSiO2-NH2 NPs showed excellent anticancer performance in both two-dimensional and three-dimensional cell models using the "one treatment, multiple irradiations" strategy.

Carbon Dots with Absorption Red-Shifting for Two-Photon Fluorescence Imaging of Tumor Tissue pH and Synergistic Phototherapy.

Phototherapy exhibits significant potential as a novel tumor treatment method, and the development of highly active photosensitizers and photothermal agents has drawn considerable attention. In this work, S and N atom co-doped carbon dots (S,N-CDs) with an absorption redshift effect were prepared by hydrothermal synthesis with lysine, o-phenylenediamine, and sulfuric acid as raw materials. The near-infrared (NIR) absorption features of the S,N-CDs resulted in two-photon (TP) emission, which has been used in TP fluorescence imaging of lysosomes and tumor tissue pH and real-time monitoring of apoptosis during tumor phototherapy, respectively. The obtained heteroatom co-doped CDs can be used not only as an NIR imaging probe but also as an effective photodynamic therapy/photothermal therapy (PDT/PTT) therapeutic agent. The efficiencies of different heteroatom-doped CDs in tumor treatment were compared. It was found that the S,N-CDs showed higher therapeutic efficiency than N-doped CDs, the efficiency of producing 1O2 was 27%, and the photothermal conversion efficiency reached 34.4%. The study provides new insight into the synthesis of carbon-based nanodrugs for synergistic phototherapy and accurate diagnosis of tumors.

Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma.

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.

Hetero-Core-Shell BiNS-Fe@Fe as a Potential Theranostic Nanoplatform for Multimodal Imaging-Guided Simultaneous Photothermal-Photodynamic and Chemodynamic Treatment.

Photothermal/photodynamic therapy (PTT/PDT) and synergistic therapeutic strategies are often sought after, owing to their low side effects and minimal invasiveness compared to chemotherapy and surgical treatments. However, in spite of the development of the most PTT/PDT materials with good tumor-inhibitory effect, there are some disadvantages of photosensitizers and photothermal agents, such as low stability and low photonic efficiency, which greatly limit their further application. Therefore, in this study, a novel bismuth-based hetero-core-shell semiconductor nanomaterial BiNS-Fe@Fe with good photonic stability and synergistic theranostic functions was designed. On the one hand, BiNS-Fe@Fe with a high atomic number exhibits good X-ray absorption, enhanced magnetic resonance (MR) T2-weighted imaging, and strong photoacoustic imaging (PAI) signals. In addition, the hetero-core-shell provides a strong barrier to decline the recombination of electron-hole pairs, inducing the generation of a large amount of reactive oxygen species (ROS) when irradiated with visible-NIR light. Meanwhile, a Fenton reaction can further increase ROS generation in the tumor microenvironment. Furthermore, an outstanding chemodynamic therapeutic potential was determined for this material. In particular, a high photothermal conversion efficiency (η = 37.9%) is of significance and could be achieved by manipulating surface decoration with Fe, which results in tumor ablation. In summary, BiNS-Fe@Fe could achieve remarkable utilization of ROS, high photothermal conversion law, and good chemodynamic activity, which highlight the multimodal theranostic potential strategies of tumors, providing a potential viewpoint for theranostic applications of tumors.

Novel Engineered Bacterium/Black Phosphorus Quantum Dot Hybrid System for Hypoxic Tumor Targeting and Efficient Photodynamic Therapy.

Intratumoral hypoxia significantly constrains the susceptibility of solid tumors to oxygen-dependent photodynamic therapy (PDT), and effort to reverse such hypoxia has achieved limited success to date. Herein, we developed a novel engineered bacterial system capable of targeting hypoxic tumor tissues and efficiently mediating the photodynamic treatment of these tumors. For this system, we genetically engineered Escherichia coli to express catalase, after which we explored an electrostatic adsorption approach to link black phosphorus quantum dots (BPQDs) to the surface of these bacteria, thereby generating an engineered E. coli/BPQDs (EB) system. Following intravenous injection, EB was able to target hypoxic tumor tissues. Subsequent 660 nm laser irradiation drove EB to generate reactive oxygen species (ROS) and destroy the membranes of these bacteria, leading to the release of catalase that subsequently degrades hydrogen peroxide to yield oxygen. Increased oxygen levels alleviate intratumoral hypoxia, thereby enhancing BPQD-mediated photodynamic therapy. This system was able to efficiently kill tumor cells in vivo, exhibiting good therapeutic efficacy. In summary, this study is the first to report the utilization of engineered bacteria to facilitate PDT, and our results highlight new avenues for BPQD-mediated cancer treatment.

NIR-Driven Intracellular Photocatalytic O2 Evolution on Z-Scheme Ni3S2/Cu1.8S@HA for Hypoxic Tumor Therapy.

Hypoxia in a tumor microenvironment (TME) has inhibited the photodynamic therapy (PDT) efficacy. Here, Ni3S2/Cu1.8S nanoheterostructures were synthesized as a new photosensitizer, which also realizes the intracellular photocatalytic O2 evolution to relieve hypoxia in TME and enhance PDT as well. With the narrow band gap (below 1.5 eV), the near infrared (NIR) (808 nm) can stimulate their separation of the electron-hole. The novel Z-scheme nanoheterostructures, testified by experimental data and density functional theory (DFT) calculation, possess a higher redox ability, endowing the photoexited holes with sufficient potential to oxide H2O into O2, directly. Meanwhile, the photostimulated electrons can capture the dissolved O2 to form a toxic reactive oxygen species (ROS). Moreover, Ni3S2/Cu1.8S nanocomposites also possess the catalase-/peroxidase-like activity to convert the endogenous H2O2 into ·OH and O2, which not only cause chemodynamic therapy (CDT) but also alleviate hypoxia to assist the PDT as well. In addition, owing to the narrow band gap, they possess a high NIR harvest and great photothermal conversion efficiency (49.5%). It is noted that the nanocomposites also exhibit novel biodegradation and can be metabolized and eliminated via feces and urine within 2 weeks. The present single electrons in Ni/Cu ions induce the magnetic resonance imaging (MRI) ability for Ni3S2/Cu1.8S. To make sure that the cancer cells were specifically targeted, hyaluronic acid (HA) was grafted outside and Ni3S2/Cu1.8S@HA integrated photodynamic therapy (PDT), chemodynamic therapy (CDT), and photothermal therapy (PTT) to exhibit the great anticancer efficiency for hypoxic tumor elimination.

Gamma and UV radiations induced treatment of anti-cancer methotrexate drug in aqueous medium: Effect of process variables on radiation efficiency evaluated using bioassays.

This studystudy focuses on the effect of radiation treatment and hydrogen peroxide (H2O2) on the toxicity of anticancer methotrexate. For cytotoxicity, different bioassays such as Allium cepa, hemolytic, brine shrimp were employed. The Ames test was used for mutagenicity analysis. The solutions having concentrations 5, 10 and 15 ppm were irradiated with UV radiation exposure time 15, 30, 45, 60, 75 and 90 min and gamma radiation absorbed doses 0.3, 0.6, 0.9, 1.2, 2, 3 and 4 kGy in combination with with H2O2. There was a clear difference observed for aqueous solution before and after treatment with reference to cytotoxicity and mutagenicity. In Allium cepa test, a 47.07, 44.36 and 38.23% increase in root length (RL), root count (RC) and mitotic index (MI) was observed, respectively, for UV/H2O2 treatment and in the case of gamma/H2O2 treatment, the RL, RC and MI were increased up to 49.39, 52.63 and 52.38%, respectively. Brine shrimp test has shown 85.95 and 91.30% decrease in toxicity using UV/H2O2 and gamma/H2O2 respectively, while hemolytic test has shown 19.21 and 26.32% hemolysis using UV/H2O2 and gamma/H2O2, respectively. The mutagenicity reduced up to 82.3, 86.46 and 89.59% (TA98) and 85.42, 87.5 and 90.63% (TA100) for UV/H2O2 while 89.59, 90.63 and 93.75% (TA98) and 84.38, 89.59 and 92.71% (TA100) for gamma/H2O2. The UV and gamma radiation along with H2O2 based AOPs are promising approaches to detoxify the wastewater which can be extended to real hospital liquid effluent effectively.

Improving the photothermal therapy efficacy and preventing the surface oxidation of bismuth nanoparticles through the formation of a bismuth@bismuth selenide heterostructure.

Bismuth (Bi) nanoparticles (NPs) are emerging as promising photothermal agents for computed tomography imaging-guided photothermal therapy. However, it is challenging to improve their photothermal conversion efficacy and prevent their oxidation. Herein, Bi@bismuth selenide (Bi2Se3) core@shell NPs were designed and fabricated for improving the photothermal performance due to the staggered energy levels between Bi and Bi2Se3. With near-infrared light irradiation, both the materials could be excited to generate hot carriers due to their extremely narrow bandgaps. The hot electrons would transfer to the conduction band of Bi2Se3 and the hot holes to the valence band of Bi, leading to the effective separation of hot carriers. Then, these hot electrons and holes would recombine nonradiatively at the interface of Bi and Bi2Se3 and produce more phonons, resulting in an enhanced photothermal conversion efficacy. Moreover, the presence of Bi2Se3 on the surface of Bi NPs could prevent Bi from surface oxidation due to the higher stability of Bi2Se3. In fact, Bi@Bi2Se3 NPs showed excellent biocompatibility and photothermal therapeutic efficacy against cancer cells.

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles.

BACKGROUND: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated. RESULTS: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation increased the proportions of G2/M phase and Caveolin-1 content in 4T1 breast cancer cells, contributing to an endocytic enhancement of PINPs@PM. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. CONCLUSION: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

A photothermal-hypoxia sequentially activatable phase-change nanoagent for mitochondria-targeting tumor synergistic therapy.

To enhance the specificity and efficiency of anti-tumor therapies, we have designed a multifunctional nanoparticle platform for photochemotherapy using fluorescence (FL) and photoacoustic (PA) imaging guidance. Nanoparticles (NPs) composed of a eutectic mixture of natural fatty acids that undergo a solid-liquid phase transition at 39 °C were used to encapsulate materials for the rapid and uniform release of the hypoxia-activated prodrug tirapazamine (TPZ) and the photosensitizer IR780, which targets the mitochondria of tumor cells and can be used to induce hypoxic cell death via photodynamic therapy and photothermal therapy. In vitro, the NPs containing TPZ and IR7890 exhibited appreciable cell uptake and triggered drug release when irradiated with a NIR laser. In vivo, photochemotherapy of the NPs achieved the best anti-tumor efficacy under PA and FL imaging guidance and monitoring. By combining IR780 mitochondria-targeting phototherapy with TPZ, we observed improved anti-tumor effectiveness and this has the potential to reduce the side effects of traditional chemotherapy. Herein, we demonstrate a new intracellular photochemotherapy nanosystem that co-encapsulates photosensitizers and hypoxia-activated drugs to enhance the overall anti-tumor effect precisely and efficiently.

Photothermal augment stromal disrupting effects for enhanced Abraxane synergy chemotherapy in pancreatic cancer PDX mode.

Cancer-associated fibroblasts (CAFs) are crucial for forming the desmoplastic stroma that is associated with chemoresistance in pancreatic ductal adenocarcinoma (PDAC). In the clinic, depleting dense stroma in PDAC tumor tissue is a promising chemotherapeutic strategy. In this study, we report that the local hyperthermia can reduce the number of CAFs in the PDAC PDX mouse mode, which further augments chemotherapeutic efficiency in the PDAC therapy. To achieve this goal, a photothermal-chemotherapeutic agent termed as Abraxane@MoSe2 as a vehicle-saving theranostic probe is prepared by simply mixing an FDA-approved Abraxane and hydrophobic MoSe2 nanosheets via electrostatic and hydrophobic interactions. After labeling with indocyanine green (ICG) dye on the Abraxane@MoSe2, a relatively high fluorescence signal (near infrared second (NIR II)) in PDX tumors can be obtained, which can be precisely imaging-guide local photothermal-chemotherapy upon the 808 nm laser irradiation in vivo. Importantly, the synergy therapeutic efficiency in PDAC is enhanced by the photothermal effect reduction of the number of CAFs, which is confirmed viaα-SMA and vimentin immunofluorescence analysis. This combined therapeutic strategy may provide a new sight for PDAC therapy.

NIR-Driven Water Splitting H2 Production Nanoplatform for H2-Mediated Cascade-Amplifying Synergetic Cancer Therapy.

As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, the high diffusivity and low solubility of hydrogen make it difficult to accumulate in local lesions. Herein, we develop a H2 self-generation nanoplatform by in situ water splitting driven by near-infrared (NIR) laser. In this work, core-shell nanoparticles (CSNPs) of NaGdF4:Yb,Tm/g-C3N4/Cu3P (UCC) nanocomposites as core encapsulated with zeolitic imidazolate framework-8 (ZIF-8) modified with folic acid as shell are designed and synthesized. Due to the acid-responsive ZIF-8 shell, enhanced permeability and retention (EPR) effect, and folate receptor-mediated endocytosis, CSNPs are selectively captured by tumor cells. Upon 980 nm laser irradiation, CSNPs exhibit a high production capacity of H2 and active oxygen species (ROS), as well as an appropriate photothermal conversion temperature. Furthermore, rising temperature increases the Fenton reaction rate of Cu(I) with H2O2 and strengthens the curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive holes produced in the valence band of g-C3N4 in the g-C3N4/Cu3P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H2 production nanoplatform is constructed for H2-mediated cascade-amplifying multimodal synergetic therapy.

One Stone Two Birds: Zr-Fc Metal-Organic Framework Nanosheet for Synergistic Photothermal and Chemodynamic Cancer Therapy.

Metal-organic frameworks (MOFs) have been identified as promising materials for the delivery of therapeutics to cure cancer owing to their intrinsic porous structure. However, in a majority of cases, MOFs act as only a delivery cargo for anticancer drugs while little attention has been focused on the utilization of their intriguing physical and chemical properties for potential anticancer purposes. Herein for the first time, an ultrathin (16.4 nm thick) ferrocene-based MOF (Zr-Fc MOF) nanosheet has been synthesized for synergistic photothermal therapy (PTT) and Fenton reaction-based chemodynamic (CDT) therapy to cure cancer without additional drugs. The Zr-Fc MOF nanosheet acts not only as an excellent photothermal agent with a prominent photothermal conversion efficiency of 53% at 808 nm but also as an efficient Fenton catalyst to promote the conversion of H2O2 into hydroxyl radical (•OH). As a consequence, an excellent therapeutic performance has been achieved in vitro as well as in vivo through this combinational effect. This work aims to construct an "all-in-one" MOF nanoplatform for PTT and CDT treatments without incorporating any additional therapeutics, which may launch a new era in the investigation of MOF-based synergistic therapy platforms for cancer therapy.