Few-Layer Bismuthene for Checkpoint Knockdown Enhanced Cancer Immunotherapy with Rapid Clearance and Sequentially Triggered One-for-All Strategy
Mengyu Guo, Xiao Zhang, Jing Liu, Fene Gao, Xiao Zhang, Xuhao Hu, Bo Li, Xu Zhang, Huige Zhou, Ru Bai, Yaling Wang, Jiayang Li, Ying Liu, Zhanjun Gu, Chunying Chen
Abstract
As a conceptually attractive strategy, the use of immune checkpoint blockade antibodies to treat cancer is limited due to the restrained tumor-infiltrating lymphocytes (TILs), poor accumulation and penetration of antibodies, and deficient checkpoint blockade in malignancies. In this study, we describe a pH and mild photothermal sequentially triggered PD-L1 siRNA release nanosystem, based on monoelemental bismuthene, as a one-for-all strategy to realize enhanced tumor mild photothermal immunotherapy. Under manually controlled NIR irradiation, the bismuthene-based nanosystem simultaneously induces a tumor-enhanced pathological permeability and retention (EPPR) effect, increases TIL recruitment, and triggers programmed siRNA release, thereby amplifying anti-PD-L1 immunotherapy. In addition, the nanosystem’s rapid removal through intestinal and renal clearance mitigates toxicity risk associated with long-term retention. In vivo antitumor experiments demonstrate that this bismuthene-based nanosystem is a promising and effective approach for “cold” tumor management.