Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

Nanoscale Metal-Organic Frameworks Combined with Metal Nanoparticles and Metal Oxide/Peroxide to Relieve Tumor Hypoxia for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is a clinically approved noninvasive tumor therapy that can selectively kill malignant tumor cells, with promising use in the treatment of various cancers. PDT is typically composed of three important parts: the specific wavelength of light, photosensitizer (PS), and oxygen. With the progressing investigation on PDT treatment, the most recent attention has focused on improving photodynamic efficiency. Tumor hypoxia has always been a critical factor hindering the efficacy of PDT. Nanoscale metal-organic frameworks (nMOF), the fourth generation of PS, present great potential in photodynamic therapy. In particular, nMOF combined with metal nanoparticles and metal oxide/peroxide has demonstrated unique properties for enhanced PDT. The metal and metal oxide nanoparticles can catalyze H2O2 to generate oxygen or automatically produces oxygen, alleviating the hypoxia and improving the photodynamic efficiency. Metal peroxide nanoparticles can spontaneously produce oxygen in water or under acidic conditions. Therefore, this Review summarizes the recent development of nMOF combined with metal nanoparticles (platinum nanoparticles and gold nanoparticles) and metal oxide/peroxide (manganese dioxide, ferric oxide, cerium oxide, calcium peroxide, and magnesium peroxide) for enhanced photodynamic therapy by alleviating tumor hypoxia. Finally, future perspectives of nMOF combined nanomaterials in PDT are put forward.

Glucose Oxidase-Modified Metal-Organic Framework for Starving-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) has been considered an emerging strategy for cancer treatment. However, the tumor microenvironment (TME) with slight acidity and restricted H2O2 limits the efficacy of CDT. Here, we report a Hf-Mn-TCPP (Hf = hafnium; Mn-TCPP = 5, 10, 15, 20-tetrakis (4-carboxyphenyl) porphyrinato-manganese (II) chloride) loaded with glucose oxidase (GOx) to realize starving-enhanced CDT. GOx consumes glucose to produce H2O2 and gluconic acid. Gluconic acid increases the acidity of TME and subsequently provides favorable conditions for the Fenton-like reaction based on Hf-Mn-TCPP. The results indicate that GOx-modified Hf-Mn-TCPP provided a great therapeutic effect in starvation-enhanced CDT in vitro and in vivo.

CeO2-Decorated Metal-Organic Framework for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is quickly developing as a hopeful cancer treatment. However, hypoxic tumors, poor targeting, and photosensitizers (PS) aggregation limited the efficiency of PDT. Here, we report a hyaluronic acid (HA)-modified CeO2-nanoparticle-decorated metal-organic framework (PCN-224@CeO2-HA) to enhance PDT and achieve targeted treatment. CeO2 catalyzes H2O2 to produce O2 to solve hypoxia problems. HA could target the CD44 receptor, which is highly expressed on the tumor cell membranes. The growth of tumor cells 4T1 and MCF-7 was controlled distinctly after being incubated with PCN-224@CeO2-HA under laser irradiation, while the survival ability of normal cell LO2 was nearly unchanged. Importantly, PCN-224@CeO2-HA could be effectively aggregated within the tumor area after 12 h of injection, and the tumor growth was remarkably inhibited under laser irradiation. PCN-224@CeO2-HA presented good biocompatibility and an excellent antitumor effect, providing a new strategy to produce O2 in situ for enhanced PDT.

Metal-organic framework combined with CaO2 nanoparticles for enhanced and targeted photodynamic therapy.

Photodynamic therapy (PDT) has been rapidly developed as an effective therapeutic approach in clinical settings. However, hypoxia seriously limits the effectiveness of PDT. Here, we report a porphyrin-based metal-organic framework combined with hyaluronate-modified CaO2 nanoparticles (PCN-224-CaO2-HA) to target and enhance PDT efficacy. CaO2 reacts with H2O or weak acid to produce O2, overcoming the hypoxia problem. Hyaluronate protects CaO2 and specifically targets the CD44 receptor, which is highly expressed on tumor cell membranes, performing targeted therapy. After PDT treatment in vitro, the survival rates of 4T1 and MCF-7 tumor cells were 14.58% and 22.45%, respectively. The fluorescence imaging showed that PCN-224-CaO2-HA effectively aggregated in the tumor after 12 h of its intravenous injection into tumor-bearing mice. PCN-224-CaO2-HA exhibited efficacious tumor growth inhibition via enhanced PDT. Overall, this nanosystem providing in situ oxygen production was successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo.