Tsai Min-Chen, Hsiao Lun-Yuan, Chang Yen-Hsuan, Chen Yu-Hsin, Hu Shang-Hsiu, Hung Chun-Yu, Chiang Wen-Hsuan
Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
ACS Appl Bio Mater. 2025 May 19;8(5):3995-4007. doi: 10.1021/acsabm.5c00144. Epub 2025 Apr 12.
The PEGylation of drug-carrying nanoparticles has often been used to prolong blood circulation and improve drug deposition at tumor sites. Nevertheless, the PEG-rich hydrophilic surfaces retard the release of the payloads and internalization of therapeutic nanoparticles by cancer cells, thus lowering the anticancer efficacy. To boost the anticancer potency of the combined photodynamic therapy (PDT) and photothermal therapy (PTT) against melanoma by conquering the PEG dilemma, herein, the hybrid PEGylated chitosan-covered polydopamine (PDA) nanoparticles (PCPNs) with acidity-elicited PEG detachment ability were fabricated as carriers of IR780, a small-molecule photosensitizer used for PTT and PDT. The IR780@PCPNs displayed a uniform, solid-like spherical shape and sound colloidal stability. Under near-infrared (NIR) irradiation, the IR780@PCPNs showed prominent photothermal conversion efficiency (ca. 54.6%), robust photothermal stability, reduced IR780 photobleaching, sufficient singlet oxygen (O) production, and glutathione-depleting ability. Moreover, with the environmental pH being reduced from 7.4 to 5.0 at 37 °C, the decreased interactions between IR780 and PCPNs due to the increased protonation of phenolic hydroxyl residues within PDA and primary amine groups of chitosan accelerated the release of IR780 species from IR780@PCPNs. Importantly, the cellular uptake of IR780@PCPNs by B16F10 melanoma was remarkably promoted in a weakly acidic milieu upon PEG detachment driven by the disintegration of acid-labile benzoic imine. With NIR irradiation, the internalized IR780@PCPNs generated hyperthermia and O to damage mitochondria, thereby effectively inhibiting the proliferation of B16F10 cells. Collectively, our findings present a practical strategy for amplifying the anticancer efficacy of PTT combined with PDT using PEG-detachable IR780@PCPNs.
负载药物的纳米颗粒聚乙二醇化常用于延长血液循环时间并改善药物在肿瘤部位的沉积。然而，富含聚乙二醇的亲水性表面会阻碍药物释放以及治疗性纳米颗粒被癌细胞内化，从而降低抗癌效果。为了克服聚乙二醇困境，提高联合光动力疗法（PDT）和光热疗法（PTT）对黑色素瘤的抗癌效力，在此，制备了具有酸引发聚乙二醇脱离能力的杂化聚乙二醇化壳聚糖包覆聚多巴胺（PDA）纳米颗粒（PCPNs），作为用于PTT和PDT的小分子光敏剂IR780的载体。IR780@PCPNs呈现均匀的类固体球形且具有良好的胶体稳定性。在近红外（NIR）照射下，IR780@PCPNs表现出显著的光热转换效率（约54.6%）、强大的光热稳定性、减少的IR780光漂白、充足的单线态氧（O）生成以及谷胱甘肽消耗能力。此外，在37℃下环境pH从7.4降至5.0时，由于PDA中酚羟基残基和壳聚糖伯胺基团质子化增加，IR780与PCPNs之间的相互作用减弱，加速了IR780物种从IR780@PCPNs的释放。重要的是，在酸不稳定的苯甲酰亚胺分解驱动的聚乙二醇脱离作用下，在弱酸性环境中，B16F10黑色素瘤细胞对IR780@PCPNs的细胞摄取显著增加。在NIR照射下，内化的IR780@PCPNs产生热疗和O以损伤线粒体，从而有效抑制B16F10细胞的增殖。总的来说，我们的研究结果提出了一种实用策略，即使用可脱离聚乙二醇的IR780@PCPNs增强PTT联合PDT的抗癌效果。
