Tumor microenvironment-responsive prodrug nanoplatform via co-self-assembly of photothermal agent and IDO inhibitor for enhanced tumor penetration and cancer immunotherapy

Biomaterials
Yijia LiuGuilei Ma

Abstract

Nanomedicine-based phototherapy in combination with immune checkpoint blockade therapy has been reported as a promising strategy for improved cancer immunotherapy. However, tumor penetration of nanomedicine into solid tumor is still an unresolved obstacle to an effective drug delivery, leading to limitations in their applications. Here, we developed a tumor microenvironment-responsive prodrug nanoplatform for efficient penetration and photo-immunotherapy of cancer. The prodrug nanoplatform is performed by integrating PEGylated indoleamine-2,3-dioxygenase (IDO) inhibitor (Epacadostat) and photosensitizer (Indocyanine green, ICG) into a core-shell nanostructure via intermolecular interactions, which can transform into small dual-drug complexes (<40 nm) at tumor microenvironment. The resulting small dual-drug complexes could undergo caveolae-mediated endocytosis, enhance cellular uptake, directly kill tumor cells, in situ trigger antitumor immune response and modulate IDO-mediated immunosuppression. More significantly, the prodrug nanoplatform in combination with PD-L1 checkpoint blockade synergistically promoted the antitumor immunity and efficiently inhibited the growth of both primary and abscopal tumors. The present study prov...Continue Reading

Citations

Jul 17, 2020·Angewandte Chemie·Jingchao LiKanyi Pu
Feb 5, 2021·ACS Biomaterials Science & Engineering·Pei-Yao XuAi-Zheng Chen
Mar 23, 2021·International Journal of Pharmaceutics·Tianming CuiLonggang Wang
Jul 28, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Asmita BanstolaSimmyung Yook
Jul 30, 2021·Advanced Science·Yuezhou ZhangWei Huang
Aug 26, 2020·ACS Applied Materials & Interfaces·Anushree SethSrikanth Singamaneni

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