期刊
BIOMATERIALS
卷 269, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120609
关键词
Melittin; Gemcitabine; Photodynamic therapy; Nanoparticle; Immunosuppression
资金
- National Natural Science Foundation of China [31771092, 32071385, 81521005, 31930066]
- Shandong Provincial Natural Science Foundation of China [ZR2019ZD25]
- Fudan-SIMM Joint Research Fund [FUSIMM20182005]
This study introduces a bioinspired tumor-responsive theranostic nanovehicle (BTN) with remarkable tumor-penetrating capability, designed to relieve the profound immunosuppression in tumor and effectively suppress tumor growth.
The robust immunosuppressive microenvironment in tumor represents a key challenge of cancer treatment, and their modulations by versatile therapeutic agents are critically hampered by the limited intratumoral delivery. Herein, we report a bioinspired tumor-responsive theranostic nanovehicle (BTN) with striking tumor-penetrating capability to relieve the profound immunosuppression in tumor for effective cancer therapy. BTN is designed by loading tumor-activated melittin pro-peptide, theranostic photochlor and reactive oxygen species (ROS)responsive prodrug of chemo-immunomodulator gemcitabine into a bioinspired lipoprotein-based nanovehicle, which display prominent tumor accumulation and flexible intratumoral permeation. Notably, the BTN-mediated combinational treatment caused drastic elimination of multiple immunosuppressive cells and remarkable infiltration of cytotoxic lymphocytes in tumor, thereby essentially relieving the tumor immunosuppression and strikingly depressing the tumor growth. Therefore, this design provides an encouraging delivery nanoplatform with distinguished immunosuppression-relieving capacity for effective cancer therapy.
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