Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, TX 76019, USA.
Acta Biomater. 2012 Aug;8(8):2996-3004. doi: 10.1016/j.actbio.2012.04.042. Epub 2012 May 3.
New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N-isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α(5)β(3) receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml(-1). Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.
新型基于磁性的核壳粒子（MBCSP）被开发出来，旨在靶向皮肤癌细胞，同时以受控方式输送化疗药物。MBCSP 由聚（N-异丙基丙烯酰胺-丙烯酰胺-烯丙胺）的温度响应性壳和嵌入磁铁矿纳米粒子的聚（乳酸-共-羟基乙酸）（PLGA）核组成。为了靶向黑色素瘤癌细胞，MBCSP 与专门结合黑色素瘤细胞的α(5)β(3)受体的 Gly-Arg-Gly-Asp-Ser（GRGDS）肽缀合。MBCSP 具有独特的多功能和控制药物释放特性。特别是，它们可以提供双重药物释放机制（通过 PLGA 核的降解实现药物的持续释放，以及通过温度响应性聚合物壳响应温度变化实现的控制释放）和双重靶向机制（磁性定位和受体介导的靶向）。体外研究结果表明，GRGDS 缀合的 MBCSP 的平均直径为 296nm，在高达 500μgml(-1)的浓度下对人真皮成纤维细胞没有细胞毒性。此外，从核心观察到姜黄素的持续释放和从 MBCSP 壳的温度依赖性释放阿霉素。这些粒子在磁共振成像中也产生了暗对比信号。最后，在 B16F10 黑色素瘤原位小鼠模型中，这些粒子在肿瘤部位聚集，特别是在存在磁铁的情况下。结果表明，MBCSP 作为一种靶向技术具有很大的潜力，用于治疗和监测黑色素瘤，以减少化疗试剂的副作用，实现靶向药物输送。
