Self-Assembling Porphyrins as a Single Therapeutic Agent for Synergistic Cancer Therapy: A One Stone Three Birds Strategy.
Combining photodynamic therapy (PDT), chemodynamic therapy (CDT), and ferroptosis is a valuable means for an enhanced anticancer effect. However, traditional combination of PDT/CDT/ferroptosis faces several hurdles, including excess glutathione (GSH) neutralization and preparation complexity. In this work, a versatile multifunctional nanoparticle (HCNP) self-assembled from two porphyrin molecules, chlorin e6 and hemin, is developed. The as-constructed HCNPs exhibit a peroxidase-mimic catalytic activity, which can lead to the in situ generation of endogenous O2, thereby enhancing the efficacy of PDT. Furthermore, the generation of hydroxyl radicals (•OH) in the tumor environment in reaction to the high level of H2O2 and the simultaneous disruption of intracellular GSH endow the HCNPs with the capacity of enhanced CDT, resulting in a more effective therapeutic outcome in combination with PDT. More importantly, GSH depletion further leads to the inactivation of GSH peroxide 4 and induced ferroptosis. Both in vitro and in vivo results showed that the combination of PDT/CDT/ferroptosis realizes highest antitumor efficacy significantly under laser irradiation. Therefore, by integrating the superiorities of O2 and •OH generation capacity, GSH-depletion effect, and bioimaging into a single nanosystem, the HCNPs are a promising single therapeutic agent for tumor PDT/CDT/ferroptosis combination therapy.
['Chen|Jun|J|', 'Chen|Feng|F|', 'Zhang|Lei|L|', 'Yang|Zhangyou|Z|', 'Deng|Tao|T|', 'Zhao|Yunfei|Y|', 'Zheng|Tianye|T|', 'Gan|Xuelan|X|', 'Zhong|Hangtian|H|', 'Geng|Yanqing|Y|', 'Fu|Xinwei|X|', 'Wang|Yuanqiang|Y|', 'Yu|Chao|C|https://orcid.org/0000-0002-8391-4080']
D000818:Animals D000970:Antineoplastic Agents D002384:Catalysis D045744:Cell Line, Tumor D002735:Chlorophyllides D005260:Female D000079403:Ferroptosis D005978:Glutathione D006427:Hemin D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D017665:Hydroxyl Radical D008027:Light D008807:Mice, Inbred BALB C D053758:Nanoparticles D009369:Neoplasms D010100:Oxygen D010778:Photochemotherapy D017319:Photosensitizing Agents D011166:Porphyrins
self-assembled porphyrin photodynamic therapy chemodynamic therapy ferroptosis combination therapy