An Antibody-like Polymeric Nanoparticle Removes Intratumoral Galectin-1 to Enhance Antitumor T-Cell Responses in Cancer Immunotherapy

Gu, Y (Gu, Yu)^{[ 1 ]} ; Zhao, Y (Zhao, Yu)^{[ 1 ]} ; Zhang, ZZ (Zhang, Zhanzhan)^{[ 1,2 ]} ; Hao, JL (Hao, Jialei)^{[ 1,2 ]} ; Zheng, YD (Zheng, Yadan)^{[ 1 ]} ; Liu, Q (Liu, Qi)^{[ 1 ]} ; Liu, Y (Liu, Yang)^{[ 1,2 ]} ; Shi, LQ (Shi, Linqi)^{[ 1,2 ]}

ACS APPLIED MATERIALS & INTERFACES, 2021, 13(19): 22159-22168

DOI: 10.1021/acsami.1c02116

摘要

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.