Tumor targeted porphyrin-based metal-organic framework for photodynamic and checkpoint blockade immunotherapy.

Photodynamic therapy (PDT) has become a promising approach and non-invasive modality for cancer treatment, however the therapeutic effect of PDT is limited in tumor metastasis and local recurrence. Herein, a tumor targeted nanomedicine (designated as PCN@HA) is constructed for enhanced PDT against tumors. By modified with hyaluronic acid (HA), which could target the CD44 receptor that expressed on the cancer cells, the targeting ability of PCN@HA has been enhanced. Under light irradiation, PCN@HA can produce cytotoxic singlet oxygen (1O2) and kill cancer cells, then eliminate tumors. Furthermore, PCN@HA exhibits fluorescence (FL)/ photoacoustic (PA) effects for multimodal imaging-guided cancer treatment. And PCN@HA-mediated PDT also can induce immunogenic cell death (ICD) and stimulate adaptive immune responses by releasing of tumor antigens. By combining with anti-PD-L1 checkpoint blockade therapy, it can not only effectively suppress the growth of primary tumor, but also inhibit the metastatic tumor growth.

Liu Y ，Zou B ，Yang K ，Jiao L ，Zhao H ，Bai P ，Tian Y ，Zhang R ... -  《-》

π-Extended Benzoporphyrin-Based Metal-Organic Framework for Inhibition of Tumor Metastasis.

Zeng JY ，Zou MZ ，Zhang M ，Wang XS ，Zeng X ，Cong H ，Zhang XZ ... -  《-》

Photodynamic Therapy Combined with Antihypoxic Signaling and CpG Adjuvant as an In Situ Tumor Vaccine Based on Metal-Organic Framework Nanoparticles to Boost Cancer Immunotherapy.

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT-induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal-organic framework (MOF)-based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF-based nanoparticles are self-assembled from H2 TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN-ACF-CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF-1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT-based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune-responses both in vitro and in vivo, which may have great potential for clinical translation in future.

Cai Z ，Xin F ，Wei Z ，Wu M ，Lin X ，Du X ，Chen G ，Zhang D ，Zhang Z ，Liu X ，Yao C ... -  《-》

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.

Yuan H ，Chen K ，Geng J ，Wu Z ，Wang C ，Shi P ... -  《-》

Nanozyme Decorated Metal-Organic Framework Nanosheet for Enhanced Photodynamic Therapy Against Hypoxic Tumor.

Li J ，Lei D ，Cao Y ，Xin F ，Zhang Z ，Liu X ，Wu M ，Yao C ... -  《International Journal of Nanomedicine》