期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 4, 页码 4861-4873出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c20268
关键词
multi-bioresponsibility; nanoparticle; chemotherapy; chemodynamic therapy; photodynamic therapy; cascade reaction
资金
- National Natural Science Foundation of China [82072060, 31801126, 31830094]
- Fundamental Research Funds for the Central Universities [XDJK2019TY002]
- Venture & Innovation Support Program for Chongqing Overseas Returnees [cx2018029]
- Chengdu Science and Technology Program [2018-CY02-00042-GX]
- 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYJC18032, ZY2016101, ZY2016203]
The combination treatment strategy of PC-Mn@Dox-NPs, incorporating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, exhibits multiple bioresponsibilities and favorable biosafety. The nanococktail achieved enhanced in vitro and in vivo anticancer efficacies compared to mono- or dual-therapeutic approaches, showing potential as a promising strategy for synergistic cancer treatment.
A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.
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