Triple-action cancer therapy using laser-activated NO-releasing metallomicellar nanophotosensitizer for pyroptosis-driven immune reprogramming.

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Tác giả: Ayeskanta Mohanty, Adityanarayan Mohapatra, In-Kyu Park, Woongkyu Park, Santhosh Kalash Rajendrakumar, Padmanaban Sathiyamoorthy, Aravindkumar Sundaram

Ngôn ngữ: eng

Ký hiệu phân loại: 133.594 Types or schools of astrology originating in or associated with a

Thông tin xuất bản: Netherlands : Journal of controlled release : official journal of the Controlled Release Society , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 160179

Cancer photoimmunotherapy represents an intelligent and highly efficient therapeutic approach that harnesses the photothermal effect to precisely target and ablate tumor tissues, while simultaneously modulating the immune system to achieve tumor elimination. The integration of multifunctional therapeutic modalities for combined photoimmunotherapy requires advanced drug delivery systems. However, the design of a single nanoagent capable of serving as a multifunctional nanophotosensitizer remains a significant challenge. In this study, we developed a metallomicellar nanophotosensitizer named TAGNO, which offers a synergistic tri-modal cancer treatment strategy by combining photothermal therapy (PTT), gas therapy (GT), and immunotherapy. The TAGNO nanophotosensitizer consists of a gold nanorod core, responsible for inducing the photothermal effect, coated with an amphiphilic polymer functionalized with tumor cell penetrating peptide to accommodate lipophilic small molecule BNN6, a nitric oxide (NO) donor for GT. We demonstrated that TAGNO exhibited high tumor accumulation, excellent stability, and biocompatibility, ensuring the safe delivery of NO to the tumor site. Upon near-infrared (NIR) laser irradiation, TAGNO effectively raised the temperature within tumor tissues while sparing the surrounding healthy tissues and enabled controlled NO release. Once released, the NO interacts with hydrogen peroxide in the hypoxic tumor microenvironment, forming peroxynitrite (ONOO
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