Photosynthetic Plant-Derived Nanovesicles Precisely Amplify Photodynamic Effect by Light-Activated Oxygen Generation for Enhanced Cancer Photoimmunotherapy.

IF 16 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Nano Pub Date : 2025-09-30 DOI:10.1021/acsnano.5c13350
Jiangang Mei,Weilun Pan,Bo Li,Mingzhen Zhong,Xiudong Shi,Yanfang Cheng,Bodeng Wu,Qi Xiu,Yicong Xue,Bo Situ,Lei Zheng
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Abstract

Photodynamic immunotherapy has emerged as a promising cancer therapeutic strategy, yet its efficacy is crucially hindered by the hypoxic and immunosuppressive tumor microenvironment (TME). Herein, we present a bioinspired nanoplatform that leverages the natural photosynthetic capabilities of spinach-derived nanovesicles (SDNV) for light-excited oxygen evolution to address this critical challenge. SDNV is engineered to encapsulate aggregation-induced emission luminogens (AIEgen), forming AIE@SDNV nanoparticles with excellent biocompatibility and transmembrane permeability. Upon irradiation, SDNV generates substantial oxygen as a substance for AIEgen to produce reactive oxygen species, thus improving the photodynamic efficacy by triggering severe cellular lipid peroxidation and calcium ion imbalance. This leads to potent tumor cell destruction and immunogenic cell death. Subsequently, significant release of damage-associated molecular patterns from tumor cells enhances systemic antitumor immunity via the cGAS-STING signaling pathway and activates immune responses within the TME. Moreover, SDNV enables precise AIEgen delivery and prolonged tumor retention. Simultaneously, AIE@SDNV-mediated photoimmunotherapy effectively suppresses both primary and distant tumors in a bilateral tumor model. This study provides a promising strategy for efficiently delivering a therapeutic agent, improving hypoxia-restricted photodynamic therapy, and reversing the immunosuppressive TME, thereby achieving potentiated antitumor efficacy and highlighting the potential of plant-derived nanovesicles in advancing cancer nanomedicine.
光合植物来源的纳米囊泡通过光活性氧生成精确放大光动力效应,增强癌症光免疫治疗。
光动力免疫疗法已成为一种很有前景的癌症治疗策略,但其疗效受到缺氧和免疫抑制肿瘤微环境(TME)的严重阻碍。在此,我们提出了一个生物启发的纳米平台,利用菠菜衍生的纳米囊泡(SDNV)的天然光合能力进行光激发氧演化,以解决这一关键挑战。SDNV被设计成包封聚集诱导发射发光原(AIEgen),形成AIE@SDNV纳米颗粒,具有优异的生物相容性和跨膜渗透性。照射后,SDNV产生大量的氧作为AIEgen产生活性氧的物质,通过引发严重的细胞脂质过氧化和钙离子失衡,从而提高光动力功效。这导致肿瘤细胞破坏和免疫原性细胞死亡。随后,肿瘤细胞大量释放损伤相关分子模式,通过cGAS-STING信号通路增强全身抗肿瘤免疫,并激活TME内的免疫反应。此外,SDNV能够精确地递送AIEgen和延长肿瘤保留时间。同时,AIE@SDNV-mediated光免疫疗法在双侧肿瘤模型中有效抑制原发和远处肿瘤。该研究为有效递送治疗剂、改善低氧限制性光动力治疗和逆转免疫抑制TME提供了一种有前途的策略,从而实现了增强的抗肿瘤功效,并突出了植物源性纳米囊泡在推进癌症纳米医学方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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