Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Small. 2017 Mar;13(10). doi: 10.1002/smll.201603121. Epub 2016 Dec 27.
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, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer-specific drug delivery. Theranostic NPs are 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) is loaded into BPLP-PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP-PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell-cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The "self-powered" immune cell-mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.
尽管在靶向药物输送系统方面已经做出了巨大努力，但目前的治疗效果仍然受到循环时间短和靶向效率有限的影响。细胞介导的药物输送和治疗诊断纳米医学的结合，有可能在治疗和诊断应用中改善癌症的管理。作者利用先天免疫细胞靶向肿瘤细胞的能力，开发了一种新的药物输送系统，利用巨噬细胞作为纳米颗粒（NP）载体和导航器，实现癌症特异性药物输送。治疗诊断 NPs 由独特的聚合物、可生物降解的发光明胶（BPLP-PLA）制成，具有强荧光、可生物降解性和细胞相容性。为了最大限度地降低癌症药物对免疫细胞和其他健康细胞的毒性，将抗 BRAF V600E 突变黑色素瘤特异性药物（PLX4032）载入 BPLP-PLA 纳米颗粒中。还将 muramyl tripeptide 连接到纳米颗粒上，以提高纳米颗粒的载药效率。所得的纳米颗粒被巨噬细胞内化，通过 BPLP-PLA 的固有荧光进行跟踪。携带纳米颗粒的巨噬细胞通过细胞间结合将药物递送至黑色素瘤细胞。药理研究还表明，载有 PLX4032 的纳米颗粒能有效杀死黑色素瘤细胞。“自供电”免疫细胞介导的药物输送系统在靶向治疗诊断癌症纳米技术方面取得了重大进展。
