Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, PR China.
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, PR China; Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024, PR China.
J Control Release. 2021 Jul 10;335:345-358. doi: 10.1016/j.jconrel.2021.05.025. Epub 2021 May 21.
Traditional combinational photodynamic therapy (PDT) and photothermal therapy (PTT) were limited in clinical therapy of cancer due to exceptionally low drug payload and activation by light with separate wavelengths. We have accidentally discovered that zinc phthalocyanine (ZNPC, a typical hydrophobic photosensitizer) and indocyanine green (ICG, a clinically approved fluorescence probe) could be co-assembled into carrier-free nanodrugs (almost 100 wt%) for single NIR laser-induced efficient PDT/PTT. Interestingly, ICG could act as "transformers" for modulating the geometric shape of ZNPC/ICG co-assembling structures from needle-like/spindle-like structure via cubic structure finally to spherical structure. Unfortunately, the nanodrugs suffered from rapid immune clearance. The ZNPC-ICG nanoprobes were further embedded into the erythrocyte membrane (RBC)-camouflaged framework. The designed ZNPC-ICG@RBC could be efficiently accumulated within the tumor sites (continue for ~60 h) and rapidly internalized into cancer cells upon laser irradiation rather than macrophage RAW264.7 cells. Compared with the free ZnPC or ICG, the biomimetic ZNPC-ICG@RBC nanoprobes exhibited amplified therapeutic effects by simultaneously producing ROS and hyperthermia, thereby synergistically improving antitumor efficiency and eliminating the tumors without any regrowth under the guidance of fluorescence imaging. The co-delivery of ZnPC and ICG via a biomimetic carrier-free system might be a promising strategy for bimodal phototherapy of cancer.
传统的联合光动力疗法（PDT）和光热疗法（PTT）由于药物负载量极低，且需要分别用不同波长的光来激活，因此在癌症的临床治疗中受到限制。我们偶然发现，酞菁锌（ZNPC，一种典型的疏水性光敏剂）和吲哚菁绿（ICG，一种临床批准的荧光探针）可以共组装成无载体的纳米药物（几乎 100wt%），用于单一近红外激光诱导的高效 PDT/PTT。有趣的是，ICG 可以作为“转换器”，调节 ZNPC/ICG 共组装结构的几何形状，从针状/纺锤状结构通过立方结构最终到球形结构。不幸的是，纳米药物会迅速被免疫清除。ZNPC-ICG 纳米探针进一步嵌入红细胞膜（RBC）伪装框架中。设计的 ZNPC-ICG@RBC 可以在激光照射下高效地在肿瘤部位积累（持续约 60h）并迅速被内化到癌细胞中，而不是巨噬细胞 RAW264.7 细胞中。与游离的 ZnPC 或 ICG 相比，仿生 ZNPC-ICG@RBC 纳米探针通过同时产生 ROS 和高热来放大治疗效果，从而协同提高抗肿瘤效率，并在荧光成像的指导下消除肿瘤而不复发。通过仿生无载体系统共递送 ZnPC 和 ICG 可能是癌症双模式光疗的一种有前途的策略。
