A tumor-to-lymph procedure navigated versatile gel system for combinatorial therapy against tumor recurrence and metastasis

Lin Qin; Jun Cao; Kun Shao; Fan Tong; Zhihang Yang; Ting Lei; Yazhen Wang; Chuan Hu; Channakeshava Sokke Umeshappa; Huile Gao; Nicholas A Peppas

doi:10.1126/sciadv.abb3116

A tumor-to-lymph procedure navigated versatile gel system for combinatorial therapy against tumor recurrence and metastasis

Sci Adv. 2020 Sep 4;6(36):eabb3116. doi: 10.1126/sciadv.abb3116. Print 2020 Sep.

Authors

Lin Qin¹, Jun Cao^{2

3}, Kun Shao⁴, Fan Tong¹, Zhihang Yang¹, Ting Lei¹, Yazhen Wang¹, Chuan Hu¹, Channakeshava Sokke Umeshappa⁵, Huile Gao⁶, Nicholas A Peppas^{3

7

8

9}

Affiliations

¹ Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
² National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
³ Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
⁴ State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China.
⁵ Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
⁶ Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. gaohuile@scu.edu.cn.
⁷ Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
⁸ Institute for Biomaterials, Drug Delivery and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA.
⁹ Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA.

Abstract

Application of cancer vaccines is limited due to their systemic immunotoxicity and inability to satisfy all the steps, including loading of tumor antigens, draining of antigens to lymph nodes (LNs), internalization of antigens by dendritic cells (DCs), DC maturation, and cross-presentation of antigens for T cell activation. Here, we present a combinatorial therapy, based on a α-cyclodextrin (CD)-based gel system, DOX/ICG/CpG-P-ss-M/CD, fabricated by encapsulating doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon irradiation, the gel system exhibited heat-responsive release of DOX and vaccine-like nanoparticles, CpG-P-ss-M, along with chemotherapy- and phototherapy-generated abundant tumor-specific antigen storage in situ. The released CpG-P-ss-M acted as a carrier adsorbed and delivered antigens to LNs, promoting the uptake of antigens by DCs and DC maturation. Notably, combined with PD-L1 blocking, the therapy effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, Non-U.S. Gov't