Tailoring Aggregation Extent of Photosensitizers to Boost Phototherapy Potency for Eliciting Systemic Antitumor Immunity

作者：Hao Zhao, Jiabao Xu, Chan Feng, Jiayu Ren, Lin Bao, Yanbing Zhao, Yanbing Zhao, Wei Tao, Yuliang Zhao, Yuliang Zhao, Xiangliang Yang · 发表于：Advanced Materials · 年份：2021 · DOI：10.1002/adma.202106390 · 被引用次数：143 · 研究领域：Nanoplatforms for cancer theranostics、Immunotherapy and Immune Responses、Photodynamic Therapy Research Studies

Abstract Phototherapy is effective for triggering the immunogenic cell death (ICD) effect. However, its efficacy is limited by low 1 O 2 generation and photothermal conversion efficacy due to two irreconcilable obstacles, namely the aggregation‐caused‐quenching (ACQ) effect and photobleaching. In this work, a discretely integrated nanofabrication (DIN) platform (Pt‐ICG/PES) is developed by facile coordination coassembly of cisplatin (Pt), photosensitizer molecules (indocyanine green (ICG)), and polymeric spacer (p(MEO 2 MA‐ co ‐OEGMA)‐ b ‐pSS (PES)). By controlling the ICG/PES feeding ratio, the aggregation of ICG can be easily tailored using PES as an isolator to balance the ACQ effect and photobleaching, thereby maximizing the phototherapy potency of Pt‐ICG/PES. With the optimized ratio of each component, Pt‐ICG/PES integrates the complementarity of photodynamic therapy, photothermal therapy, and chemotherapeutics to magnify the ICD effect, exerting a synergistic antitumor immunity‐promoting effect. Additionally, temperature‐sensitive PES enables photothermally guided drug delivery. In a tumor‐bearing mouse model, Pt‐ICG/PES elicits effective release of danger‐associated molecular patterns, dendritic cell maturation, cytotoxic T lymphocytes activation, cytokine secretion, M2 macrophage repolarization, and distal tumor suppression, confirming the excellent in situ tumor ICD effect as well as robust systematic antitumor immunity. Ultimately, a versatile DIN strategy is develo...