Magnetoresponsive Virus-Mimetic Nanocapsules with Dual Heat-Triggered Sequential-Infected Multiple Drug-Delivery Approach for Combinatorial Tumor Therapy
Magnetoresponsive Virus-Mimetic Nanocapsules with Dual Heat-Triggered Sequential-Infected Multiple Drug-Delivery Approach for Combinatorial Tumor Therapy
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DOI：
10.1002/smll.201402969
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发表时间：
2015-05-27
期刊：
影响因子：
13.3
通讯作者：
Hu, Shang-Hsiu
中科院分区：
文献类型：
--
作者：
Fang, Jen-Hung;Lee, Yun-Ting;Hu, Shang-Hsiu
刺激响应性药物递送系统构成了一种有吸引力的方法来引导和限制药物在特定感兴趣部位的时空释放。然而，由于天然肿瘤屏障的存在，大多数系统难以影响肿瘤组织中的每个癌细胞，导致潜在的肿瘤复发。在这里，核-壳磁响应病毒模拟纳米胶囊（VNs），它可以感染癌细胞顺序和双重作为磁热剂制造通过锚定氧化铁纳米粒子在单组分蛋白质（乳铁蛋白）壳，报告。由于具有大的亲水/疏水抗癌货物，多柔比星和paliclavin的有效载荷，VN可以在施加外部高频磁场（HFMF）的同时提供快速的药物释放和强烈的热量。此外，在通过HFMF操作从死细胞中释放后，构建性VN可以依次感染邻近的癌细胞并将足够的治疗剂递送到下一个靶向部位。由于连续细胞感染的高效率，VN在组合治疗后成功地消除了皮下肿瘤。这些结果表明，VN可用于局部靶向的、按需的磁响应化疗/热疗，结合重复细胞感染用于肿瘤治疗和其他治疗应用。
Stimuli-responsive drug-delivery systems constitute an appealing approach to direct and restrict drug release spatiotemporally at the specific site of interest. However, it is difficult for most systems to affect every cancer cell in a tumor tissue due to the presence of the natural tumor barrier, leading to potential tumor recurrence. Here, core-shell magnetoresponsive virus-mimetic nanocapsules (VNs), which can infect cancer cells sequentially and double as a magnetothermal agent fabricated through anchoring iron oxide nanoparticles in a single-component protein (lactoferrin) shell, are reported. With large payload of hydrophilic/hydrophobic anticancer cargos, doxorubicin and palictaxel, VNs can simultaneously give a rapid drug release and intense heat while applying an external high-frequency magnetic field (HFMF). Furthermore, after being liberated from dead cells by HFMF manipulation, the constructive VNs can sequentially infect neighboring cancer cells and deliver sufficient therapeutic agents to next targeted sites. With high efficiency for sequential cell infections, VNs have successfully eliminated subcutaneous tumor after a combinatorial treatment. These results demonstrate that the VNs could be used for locally targeted, on-demand, magnetoresponsive chemotherapy/hyperthermia, combined with repeated cell infections for tumor therapy and other therapeutic applications.