Kang Weiyan, Zhao Feng, Cheng Jixing, Feng Kaijie, Yan Liang, You Yue, Li Jinxia, Meng Jing
Department of Medicinal Chemistry, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
Nanomaterials (Basel). 2025 Jun 9;15(12):889. doi: 10.3390/nano15120889.
The present study compared the free and encapsulated photosensitizer hypocrellin B (HB) in terms of photophysical-chemical properties, cellular uptake, subcellular distribution, and phototoxicity. The hydrophobic HB was encapsulated into liposomes (HB@Lipo) or poly (lactic--glycolic acid) nanoparticles (HB@PLGA). Encapsulation into nanocarriers exerted no obvious influence on the photophysical-chemical properties of HB, including UV-visible absorbance, fluorescence spectra, singlet oxygen (O) production capacity, and photostability. Free and encapsulated HB revealed some disparities in cellular uptake and subcellular localization patterns. In 2D-cultured B16 cells and tumor spheroids, free HB exhibited the fastest cellular uptake, while HB@PLGA had the lowest, as evidenced. Subcellular localization analysis first revealed a significant colocalization of free HB, HB@Lipo, and HB@PLGA within lipid droplets, with minimal colocalization in mitochondria and the endoplasmic reticulum. Unlike free HB and HB@Lipo, HB@PLGA exhibited strong lysosomal colocalization, indicating a unique intracellular trafficking pathway for PLGA-encapsulated HB. Upon laser irradiation, both free and encapsulated HB induced pronounced phototoxicity with substantial ROS production, confirming the robust PDT effect of HB. The photodynamic killing effect correlated with the intracellular HB content. These findings highlighted the impact of nanoformulation on HB's cellular behavior and therapeutic performance.
本研究比较了游离型和包封型光敏剂竹红菌素B（HB）在光物理化学性质、细胞摄取、亚细胞分布和光毒性方面的差异。疏水性的HB被包封到脂质体（HB@Lipo）或聚（乳酸-乙醇酸）纳米颗粒（HB@PLGA）中。包封到纳米载体中对HB的光物理化学性质没有明显影响，包括紫外可见吸收、荧光光谱、单线态氧（O）产生能力和光稳定性。游离型和包封型HB在细胞摄取和亚细胞定位模式上存在一些差异。在二维培养的B16细胞和肿瘤球体中，游离型HB表现出最快的细胞摄取，而HB@PLGA的摄取最低，已有证据证明。亚细胞定位分析首先揭示了游离型HB、HB@Lipo和HB@PLGA在脂滴中有显著的共定位，而在线粒体和内质网中的共定位最少。与游离型HB和HB@Lipo不同，HB@PLGA表现出强烈的溶酶体共定位，表明PLGA包封的HB有独特的细胞内运输途径。激光照射后，游离型和包封型HB均通过大量活性氧产生诱导明显的光毒性，证实了HB强大的光动力治疗效果。光动力杀伤效果与细胞内HB含量相关。这些发现突出了纳米制剂对HB细胞行为和治疗性能的影响。
