College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
ACS Appl Mater Interfaces. 2020 Dec 23;12(51):56767-56781. doi: 10.1021/acsami.0c17235. Epub 2020 Dec 8.
The consolidation of nanovectors with biological membranes has recently been a subject of interest owing to the prolonged systemic circulation time and delayed clearance by the reticuloendothelial system of such systems. Among the different biomembranes, the macrophage membrane has a similar systemic circulation time, with an additional chemotactic aptitude, targeting integrin proteins. In this study, we aimed to establish a laser-activated, disintegrable, and deeply tumor-penetrative nanoplatform. We used a highly tumor-ablative and laser-responsive disintegrable copper sulfide nanoparticle, loaded it with paclitaxel, and camouflaged it with the macrophage membrane for the fabrication of PTX@CuS@MMNPs. The paclitaxel release profile was favorable for release in the tumor microenvironment, and the release was accelerated after laser exposure. Cellular internalization was improved by membrane encapsulation. Cellular uptake, cytotoxicity, reactive oxygen species generation, and apoptosis induction of PTX@CuS@MMNPs were further improved upon laser exposure, and boosted permeation was achieved by co-administration of the tumor-penetrating peptide iRGD. tumor accumulation, tumor inhibition rate, and apoptotic marker expression induced by PTX@CuS@MMNPs were significantly improved by laser irradiation and iRGD co-administration. PTX@CuS@MMNPs induced downregulation of cellular proliferation and angiogenic markers but no significant changes in body weight, survival, or significant toxicities in vital organs after laser exposure, suggesting their biocompatibility. The disintegrability of the nanosystem, accredited to biodegradability, favored efficient elimination from the body. In conclusion, PTX@CuS@MMNPs showed promising traits in combination therapies for excellent tumor eradication.
纳米载体与生物膜的融合最近成为研究热点，因为这种系统可以延长系统循环时间并延迟网状内皮系统的清除。在不同的生物膜中，巨噬细胞膜具有相似的系统循环时间，并且具有趋化性，靶向整合蛋白。在这项研究中，我们旨在建立一种激光激活、可分解和深度穿透肿瘤的纳米平台。我们使用了一种高度肿瘤消融和激光响应的可分解硫化铜纳米颗粒，将其装载紫杉醇，并将其伪装成巨噬细胞膜，以制备 PTX@CuS@MMNPs。紫杉醇的释放曲线有利于在肿瘤微环境中释放，并且激光照射后释放加速。通过膜封装提高了细胞内化。激光照射后，PTX@CuS@MMNPs 的细胞摄取、细胞毒性、活性氧生成和细胞凋亡诱导进一步提高，并且通过共给药穿透肽 iRGD 实现了增强的渗透。PTX@CuS@MMNPs 的肿瘤积累、肿瘤抑制率和凋亡标志物表达通过激光照射和 iRGD 共给药显著提高。PTX@CuS@MMNPs 诱导细胞增殖和血管生成标志物下调，但激光照射后体重、存活或重要器官无明显毒性变化，表明其生物相容性。纳米系统的可分解性归因于生物降解性，有利于从体内有效消除。总之，PTX@CuS@MMNPs 在联合治疗中显示出良好的肿瘤消除潜力。
