Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery.
Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery.
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DOI：
10.1002/smll.201603121
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Xie Z;Su Y;Kim GB;Selvi E;Ma C;Aragon-Sanabria V;Hsieh JT;Dong C;Yang J
尽管在靶向给药系统方面已经做出了巨大的努力，但目前的治疗结果仍然存在循环时间短和靶向效率有限的问题。细胞介导的药物传递和治疗纳米药物的集成可能会在治疗和诊断应用中改善癌症的管理。通过利用先天免疫细胞靶向肿瘤细胞的能力，我们开发了一种新型的药物传递系统，利用巨噬细胞作为纳米颗粒载体和导航器来实现肿瘤特异性药物传递。以一种独特的聚合物--可生物降解的光致发光聚乳酸(BPLP-PLA)为原料，制备了具有强荧光、生物可降解性和细胞相容性的医用纳米颗粒。为了将抗癌药物对免疫细胞和其他健康细胞的毒性降至最低，将抗BRAF V600E突变黑色素瘤特异性药物(PLX4032)负载到BPLP-PLA纳米粒中。纳米粒上还偶联了胞壁三肽(MTP)，提高了纳米粒的载药效率。生成的纳米颗粒被内化在巨噬细胞中，并通过BPLP-PLA的本征荧光进行跟踪。携带纳米颗粒的巨噬细胞通过细胞与细胞的结合将药物输送到黑色素瘤细胞。药理学研究还表明，负载PLX4032的纳米颗粒有效地杀死了黑色素瘤细胞。我们的“自供电”免疫细胞介导的药物传递系统展示了靶向治疗癌症纳米技术的潜在重大进步。
Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell’s ability to target tumor cells, we developed a novel drug delivery system by using macrophages as both nanoparticle-carriers and navigators to achieve cancer-specific drug delivery. Theranostic nanoparticles were fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti-BRAF V600E mutant melanoma specific drug (PLX4032) was loaded into BPLP-PLA nanoparticles. Muramyl tripeptide (MTP) was also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles were internalized within macrophages, which were tracked via the intrinsic fluorescence of BPLP-PLA. Macrophages carrying nanoparticles delivered drugs to melanoma cells via cell-cell binding. Pharmacological studies also indicated that the PLX4032 loaded nanoparticles effectively killed melanoma cells. Our “self-powered” immune cell-mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.