Key Laboratory for Organic Electronics & Information Displays and Institute of Advanced Materials, Nanjing University of Posts and Telecommunications , Nanjing 210046, P. R. China.
Department of Radiotherapy, the Second Affiliated Hospital of Nanjing Medical University , Nanjing 210011, P. R. China.
ACS Appl Mater Interfaces. 2016 Jul 20;8(28):17927-35. doi: 10.1021/acsami.6b05677. Epub 2016 Jul 7.
Mesenchymal stem cells (MSCs) have attracted increasing attention as vehicles for cancer treatment. Herein, MSC-based synergistic oncotherapy strategy is presented for the first time. To achieve this goal, yolk-shell structured gold nanorod embedded hollow periodic mesoporous organosilica nanospheres (GNR@HPMOs) with high paclitaxel (PTX) loading capability and excellent photothermal transfer ability upon near-infrared (NIR) light irradiation are first prepared. Cytotoxicity and migration assays show that the viability and tumor-homing capability of MSCs are well-retained after internalization of high content of PTX loaded GNR@HPMOs (denoted as GNR@HPMOs-PTX). In vitro experiments show the GNR@HPMOs-PTX loaded MSCs (GNR@HPMOs-PTX@MSCs) possess synergistic chemo-photothermal killing effects for breast cancer cells. Also, photoacoustic imaging shows that the MSCs can improve dispersion and distribution in tumor tissue for GNR@HPMOs-PTX after intratumoral injection. In vivo experiments in breast cancer model of nude mice further demonstrate that the GNR@HPMOs-PTX@MSCs significantly inhibit tumor growth, suggesting their great potential for synergistic therapy of cancer.
间充质干细胞(MSCs)作为癌症治疗的载体引起了越来越多的关注。本文首次提出了基于 MSC 的协同肿瘤治疗策略。为此,我们首次制备了具有高紫杉醇(PTX)载药能力和近红外(NIR)光照射下优异光热传递能力的蛋黄壳结构金纳米棒嵌入中空周期性介孔有机硅纳米球(GNR@HPMOs)。细胞毒性和迁移实验表明,在高含量载药 GNR@HPMOs(记为 GNR@HPMOs-PTX)内化后,MSCs 的活力和肿瘤归巢能力保持良好。体外实验表明,负载 GNR@HPMOs-PTX 的 MSC(GNR@HPMOs-PTX@MSCs)对乳腺癌细胞具有协同的化疗-光热杀伤作用。此外,光声成像显示,在肿瘤内注射后,MSC 可以改善 GNR@HPMOs-PTX 在肿瘤组织中的分散和分布。在裸鼠乳腺癌模型的体内实验进一步证明,GNR@HPMOs-PTX@MSCs 可显著抑制肿瘤生长,表明其在癌症协同治疗方面具有巨大潜力。