Institute of Urology, Southeast University Medical College, Nanjing 210009, China.
The State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210009, China.
Int J Mol Sci. 2022 Mar 26;23(7):3623. doi: 10.3390/ijms23073623.
Castration-resistant prostate cancer (CRPC) is the most common malignant tumor of the male urinary system. Nanodrug delivery systems (NDDS) have been widely applied in drug delivery for tumor therapy; however, nanotherapeutics encounter various biological barriers that prevent successful accumulation of drugs, specifically at diseased sites. Therefore, there is an urgent need to develop a CRPC-targeting nanocomposite with fine biocompatibility for penetrating various biological barriers, delivering sufficient drugs to the targeting site and improving therapeutic efficiency. In this work, CRPC cell membranes were firstly adapted as biomimetic vectors for the encapsulating PEG-PLGA polymer containing the chemotherapy drug docetaxel (DTX). The CRPC membrane-camouflaged nanoparticles can easily escape early recognition by the immune system, penetrate the extracellular barrier, and evade clearance by the circulatory system. In addition to the characteristics of traditional nanoparticles, the CRPC cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize the same cancer cell types and increase the targeted drug delivery of DTX. In vivo fluorescence and radionuclide dual-model imaging were fulfilled by decorating the biomimetic nanosystem with near-infrared dye and isotope, which validated the homotypic targeting property offered by the CRPC cell membrane coating. Importantly, remarkably improved therapeutic efficacy was achieved in a mice model bearing CRPC tumors. This homologous cell membrane enabled an efficient drug delivery strategy and enlightened a new pathway for the clinical application of tumor chemotherapy drugs in the future.
去势抵抗性前列腺癌（CRPC）是男性泌尿系统最常见的恶性肿瘤。纳米药物递送系统（NDDS）已广泛应用于肿瘤治疗的药物递送；然而，纳米疗法遇到了各种生物屏障，阻止了药物的成功积累，特别是在病变部位。因此，迫切需要开发一种具有精细生物相容性的 CRPC 靶向纳米复合材料，以穿透各种生物屏障，将足够的药物递送到靶向部位，并提高治疗效率。在这项工作中，首先将 CRPC 细胞膜用作包封含有化疗药物多西紫杉醇（DTX）的聚乙二醇-聚乳酸共聚物的仿生载体。CRPC 膜伪装的纳米颗粒可以轻易逃避免疫系统的早期识别，穿透细胞外屏障，并逃避循环系统的清除。除了传统纳米颗粒的特性外，CRPC 细胞膜还包含一系列高度特异性的同种型部分，可用于识别相同的癌细胞类型，并增加 DTX 的靶向药物递送。通过用近红外染料和同位素修饰仿生纳米系统，实现了体内荧光和放射性核素双模成像，验证了 CRPC 细胞膜涂层提供的同种型靶向特性。重要的是，在携带 CRPC 肿瘤的小鼠模型中实现了显著提高的治疗效果。这种同源细胞膜提供了一种有效的药物递送策略，为肿瘤化疗药物的临床应用开辟了新途径。
