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

Phototherapy is an effective therapy for triggering the immunogenic cell death (ICD) effect. However, its efficacy is limited by low 1 O2 generation and photothermal conversion efficacy due to two irreconcilable obstacles, namely aggregation-caused-quenching (ACQ) effect and photo-bleaching. Herein, a discretely integrated nanofabrication platform (Pt-ICG/PES) is developed by facile coordination co-assembly of cisplatin (Pt), photosensitizer molecules (indocyanine green [ICG]), and polymeric spacer (p(MEO2 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 photo-bleaching, 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 anti-tumor immunity-promoting effect. Additionally, temperature-sensitive PES enables photothermal guided drug delivery. In the 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, we develop a versatile discretely integrated nanofabrication strategy to optimize the phototherapeutic efficacy for improving antitumor effects and strengthening systemic antitumor immunity. This article is protected by copyright. All rights reserved.