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Albumin-Gold Nanorod Nanoplatform for Cell-Mediated Tumoritropic Delivery with Homogenous ChemoDrug Distribution and Enhanced Retention Ability
Theranostics ( IF 12.4 ) Pub Date : 2017-07-22 , DOI: 10.7150/thno.19279
Hsien-Ting Chiu , Cheng-Kuan Su , Yuh-Chang Sun , Chi-Shiun Chiang , Yu-Fen Huang

Recently, living cells with tumor-homing properties have provided an exciting opportunity to achieve optimal delivery of nanotherapeutic agents. However, premature payload leakage may impair the host cells, often leading to inadequate in vivo investigations or therapeutic efficacy. Therefore, a nanoplatform that provides a high drug-loading capacity and the precise control of drug release is required. In the present study, a robust one-step synthesis of a doxorubicin (DOX)-loaded gold nanorod/albumin core-shell nanoplatform (NR@DOX:SA) was designed for effective macrophage-mediated delivery to demonstrate how nanoparticle-loaded macrophages improve photothermal/chemodrug distribution and retention ability to achieve enhanced antitumor effects. The serum albumin shell of these nanoagents served as a drug reservoir to delay the intracellular DOX release and drug-related toxicity that impairs the host cell carriers. Near-infrared laser irradiation enabled on-demand payload release to destroy neighboring tumor cells. A series of in vivo quantitative analyses demonstrated that the nanoengineered macrophages delivered the nanodrugs through tumor-tropic migration to tumor tissues, resulting in the twice homogenous and efficient photothermal activations of drug release to treat prostate cancer. By contrast, localized pristine NR@DOX:SAs exhibit limited photothermal drug delivery that further reduces their retention ability and therapeutic efficacy after second combinational treatment, leading to a failure of cancer therapy. Moreover, the resultant unhealable wounds impair quality of life. Free DOX has rapid clearance and therefore exhibits limited antitumor effects. Our findings suggest that in comparison with pristine nanoparticles or free DOX, the nanoengineered macrophages effectively demonstrate the importance and effect of homogeneous drug distribution and retention ability in cancer therapy.

中文翻译:

白蛋白-金纳米棒纳米平台用于细胞介导的均质化学分布和增强的保留能力的促肿瘤递送。

最近,具有肿瘤归巢特性的活细胞为实现纳米治疗剂的最佳递送提供了令人兴奋的机会。然而,过早的有效负载泄漏可能会损害宿主细胞,从而经常导致体内不足调查或疗效。因此,需要提供高载药量和精确控制药物释放的纳米平台。在本研究中,设计了一种稳定的一步法合成负载阿霉素(DOX)的金纳米棒/白蛋白核-壳纳米平台(NR @ DOX:SA),以有效地巨噬细胞介导的递送,以证明负载纳米颗粒的巨噬细胞如何改善光热/化学药物的分布和保留能力可实现增强的抗肿瘤作用。这些纳米剂的血清白蛋白壳充当药物贮存库,以延迟细胞内DOX释放和损害宿主细胞载体的药物相关毒性。近红外激光照射可按需释放有效载荷,以破坏邻近的肿瘤细胞。一系列体内定量分析表明,纳米工程巨噬细胞通过向肿瘤的向肿瘤组织的迁移传递了纳米药物,从而导致了两次均一且有效的光热活化药物释放,从而治疗了前列腺癌。相比之下,局部原始NR @ DOX:SAs表现出有限的光热药物传递,这在第二次联合治疗后进一步降低了其保留能力和治疗功效,从而导致癌症治疗失败。此外,所导致的无法治愈的伤口损害了生活质量。游离DOX具有快速清除能力,因此显示出有限的抗肿瘤作用。我们的发现表明,与原始纳米颗粒或游离DOX相比,
更新日期:2017-12-01
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