Nanoscale Coordination Polymers Codeliver Carboplatin and Gemcitabine for Highly Effective Treatment of Platinum-Resistant Ovarian Cancer

Due to the ability of ovarian cancer (OCa) to acquire drug resistance, it has been difficult to develop efficient and safe chemotherapy for OCa. Here, we examined the therapeutic use of a new self-assembled core–shell nanoscale coordination polymer nanoparticle (NCP-Carbo/GMP) that delivers high loadings of carboplatin (28.0 ± 2.6 wt %) and gemcitabine monophosphate (8.6 ± 1.5 wt %). A strong synergistic effect was observed between carboplatin and gemcitabine against platinum-resistant OCa cells, SKOV-3 and A2780/CDPP, <i>in vitro</i>. The coadministration of carboplatin and gemcitabine in the NCP led to prolonged blood circulation half-life (11.8 ± 4.8 h) and improved tumor uptake of the drugs (10.2 ± 4.4% ID/g at 24 h), resulting in 71% regression and 80% growth inhibition of SKOV-3 and A2780/CDDP tumors, respectively. Our findings demonstrate that NCP particles provide great potential for the codelivery of multiple chemotherapeutics for treating drug-resistant cancer

Photodynamic Therapy Mediated by Nontoxic Core–Shell Nanoparticles Synergizes with Immune Checkpoint Blockade To Elicit Antitumor Immunity and Antimetastatic Effect on Breast Cancer

An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore, immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1 breast tumor but also significantly preventing metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results in the eradication of light-irradiated primary tumors and the complete inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T cell response. These findings indicate that nanoparticle-mediated PDT can potentiate the systemic efficacy of checkpoint blockade immunotherapies by activating the innate and adaptive immune systems in tumor microenvironment

Nanoscale Metal–Organic Frameworks for Ratiometric Oxygen Sensing in Live Cells

We report the design of a phosphorescence/fluorescence dual-emissive nanoscale metal–organic framework (NMOF), R-UiO, as an intracellular oxygen (O₂) sensor. R-UiO contains a Pt­(II)-porphyrin ligand as an O₂-sensitive probe and a Rhodamine-B isothiocyanate ligand as an O₂-insensitive reference probe. It exhibits good crystallinity, high stability, and excellent ratiometric luminescence response to O₂ partial pressure. <i>In vitro</i> experiments confirmed the applicability of R-UiO as an intracellular O₂ biosensor. This work is the first report of a NMOF-based intracellular oxygen sensor and should inspire the design of ratiometric NMOF sensors for other important analytes in biological systems

A thermosensitive hydrogel-copper meta-organic framework composite improves hindlimb ischemia therapy through synergistically enhancing HIF-1α production and inhibiting HIF-1α degradation

Critical limb ischemia (CLI) remains a significant clinical challenge with high morbidity and mortality. Considering the critical role of hypoxia-inducible factor 1α (HIF-1α) in hypoxic site to induce angiogenesis by regulating the expression of growth factors, we prepared a cooperative composite (P-F-HKUST-1) by mixing thermo-responsive hydrogel (PPCN) with folic acid modified copper-based MOFs (F-HKUST-1) for the hindlimb ischemia therapy. The gelation of P-F-HKUST-1 in hindlimb muscle generated a more serious ischemia environment and subsequently induced the expression of HIF-1α, while the slowly released Cu2+ from P-F-HKUST-1 increased HIF-1α stability by inactivating the factor-inhibiting hypoxia-inducible factor 1 (FIH-1), which synergistically induced the productions of downstream growth factors and finally restored the blood perfusion rapidly. In addition, P-F-HKUST-1 hydrogel exhibited a long in vivo retention time, which endowed the sustaining action on HIF-1α to reduce the frequency of administration. The rapid blood flow recovery, together with the good biocompatibility suggested that P-F-HKUST-1 could be a potential novel combined therapy (HIF-1α stimulation and stabilization) for critical limb ischemia