目的 ·制备在近红外光诱导下实现粒径可变（大变小）的阿霉素（ doxorubicin，DOX）纳米递送系统，并考察其光促粒径转换性能及细胞毒性。方法 ·通过滴加法合成载 DOX的聚乙二醇 –聚乳酸 [poly(ethylene glycol)-polylactide，PEG-PLA]纳米粒，采用薄膜水化法将 PEG-PLA-DOX包载入脂质体（ liposome，LP）内水腔，并在 LP双分子层间加入光敏剂维替泊芬（ verteporfin，VP），合成对近红外光敏感的纳米粒（ PEG-PLA-DOX@LP）。利用透射电子显微镜观察各步骤纳米粒形态结构；动态光散射激光粒度仪检测各阶段纳米粒的粒径；评估纳米粒的载药性能和光诱导下的纳米粒尺寸可变行为；考察纳米粒的稳定性及光诱导粒径变化对小鼠黑色素瘤 B16F10细胞活力的影响。结果 ·成功合成了 PEG-PLA-DOX@LP光敏感纳米粒，其粒径为（ 194.83±5.70）nm，Zeta表面电势为（-1.43±0.32）mV，DOX载药量 2.82%，VP载药量 1.16%；光照前 LP结构完整，光照后可明显看到粒径为（ 37.42±8.67）nm的 PEG-PLA-DOX从 LP中释放；载药纳米粒尺寸显著缩小，产生更有效杀伤肿瘤细胞的作用。结论 ·构建的新型 DOX纳米递送系统可在近红外光诱导下，使药物粒径快速由大变小，增强对肿瘤细胞的杀伤作用。

Objective · To engineer a light-induced size-switchable (large to small) nanosystem for doxorubicin (DOX) delivery and characterize its light-induced size change and cytotoxicity. Methods · The poly(ethylene glycol)-polylactide nanoparticles loading DOX (PEG-PLA-DOX) were fabricated with the dropwise addition method. Then the nanoparticles were encapsulated into the inner cavity of liposome (LP), and a photosensitizer (verteporfin, VP) was loaded in the bilayers of the LP to engineer the near-infrared light-sensitive core-shell nanoparticles (PEG-PLA-DOX@LP). The morphology of the nanoparticles was observed under a transmission electron microscope. Dynamic light scattering was used to examine the particle size at each stage. The size-switchable property of the nanoparticles and its influence on viability of murine melanoma B16F10 cells under near-infrared light were evaluated. The stability of the nanoparticles was also investigated. Results · PEG-PLA-DOX@LP, the light-sensitive nanoparticles, were successfully developed. The nanoparticles had a particle size of (194.83±5.70) nm and Zeta potential of (-1.43±0.32) mV. The drug loading was 2.82% for DOX, and 1.16% for VP. The small-sized PEG-PLA-DOX [(37.42±8.67) nm]was quickly released the nanoparticles upon light for enhanced toxicity to B16F10 murine melanoma cells. Conclusion · The particle size of the novel DOX delivery nanosystem rapidly changes large size to small size upon the irradiation of near-infrared light, and thus the cytotoxic effect on tumor cells can be enhanced. [Key words]near-infrared light; doxorubicin; nanoparticle; size-switchable[National Natural Science Foundation of China, 81773274; Foundation of Shanghai Local High Level University (First-class Discipline–Pharmacy) ]。