Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan, ROC.
Biomaterials. 2016 Sep;101:241-50. doi: 10.1016/j.biomaterials.2016.06.008. Epub 2016 Jun 4.
Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment.
联合化疗通常需要多种药物，按照不同的方案进行多次注射，而药物分子在适当的时间到达病变组织并达到有效治疗浓度的概率非常低。本工作阐明了一种可注射的共递药系统，它基于阳离子脂质体，通过静电相互作用吸附在阴离子空心微球（Lipos-HMs）上，通过外部施加的高频磁场（HFMF）以热驱动的方式，可以实现局部序列特异性释放化学预防剂（1,25(OH)2D3）和抗癌药物（阿霉素；DOX），时间可控。Lipos-HMs 通过降低抗氧化酶（超氧化物歧化酶）的细胞质表达，极大地促进了肿瘤细胞中活性氧（ROS）的积累，从而增加了癌细胞对 DOX 的细胞毒性作用的敏感性。在携带异种移植肿瘤的裸鼠中，在 HFMF 暴露下用 Lipos-HMs 治疗可有效抑制肿瘤生长，是所有研究中最有效的治疗干预措施。这些实验结果表明，Lipos-HMs 中顺序释放 1,25(OH)2D3 和 DOX 的协同抗癌作用可能具有最大化 DOX 细胞毒性的潜力，从而支持更有效的癌症治疗。
