Light‐Driven Self‐Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption

• Published in: Advanced materials (Weinheim) Vol. 35; no. 24; pp. e2210920 - n/a
• Main Authors: Li, Haoze, Zhou, Sensen, Wu, Min, Qu, Rui, Wang, Xin, Chen, Weizhi, Jiang, Yuyan, Jiang, Xiqun, Zhen, Xu
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2023
• Subjects: Biocompatibility; biomimetic semiconducting polymer nanoparticles; Biomimetics; Blood Platelets; Blood vessels; Cell Line, Tumor; Coagulation; Disruption; Hemorrhage; Humans; Hyperthermia; light‐driven self‐recruitment; Materials science; Nanoparticles; Nanoparticles - therapeutic use; Neoplasms - drug therapy; Neoplasms - pathology; Polymers; Polymers - therapeutic use; Recruitment; reversion of immunosuppression; Toxicity; Tumor Microenvironment; tumor vascular disruption; Tumors; light-driven self-recruitment; reversion of immunosuppression; tumor vascular disruption; biomimetic semiconducting polymer nanoparticles
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202210920

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off‐target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA‐free biomimetic semiconducting polymer nanoparticle (SPNP) is herein reported for precise tumor vascular disruption through two‐stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid‐derived suppressor cells. Therefore, this study not only illustrates a light‐driven self‐recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies. A novel VDA‐free biomimetic semiconducting polymer nanoparticle (SPNP) that consists of a photothermal semiconducting polymer agent camouflaged with a platelet membrane is developed. SPNP exhibits a photothermally controlled recruitment behavior that augments targeting and accumulation of SPNP specifically around injured tumor vessels, achieving precise tumor vascular disruption, inhibition of splenomegaly, and reversion of immunosuppressive tumor microenvironment through two‐stage light manipulation.