Tumor-permeated bioinspired theranostic nanovehicle remodels tumor immunosuppression for cancer therapy

Abstract

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.

Keywords: Gemcitabine; Immunosuppression; Melittin; Nanoparticle; Photodynamic therapy.