College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea.
College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong Dongjak-gu, Seoul 156-756, Republic of Korea.
Colloids Surf B Biointerfaces. 2017 Dec 1;160:73-83. doi: 10.1016/j.colsurfb.2017.09.010. Epub 2017 Sep 8.
Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer. Bortezomib was loaded within the lipid bilayers, while gemcitabine was loaded into the hydrophilic interior of the porous GNS via an ammonium sulfate-driven pH gradient method. Physicochemical characterizations and biological studies of GNS-L/GB were performed, with the latter using cytotoxicity assays, cellular uptake and apoptosis assays, live/dead assays, and western blot analysis of pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). The nanoshells showed remotely controllable drug release when exposed to near-infrared laser for site-specific delivery. GNS-L/GB showed synergistic cytotoxicity and improved internalization by cancer cells. High-powered near-infrared continuous wave laser (λ=808nm) effectively killed cancer cells via the photothermal effect of GNS-L/GB, irrespective of cell type in a power density-, time-, and GNS dose-dependent manner. These results suggest that this method can provide a novel approach to achieve synergistic combinational chemotherapy and photothermal therapy, even with resistant pancreatic cancer.
胰腺癌预后极差,85%的死亡率归因于其侵袭性和无症状生长、高转移性潜能以及对已无效的化疗迅速产生耐药性。在本研究中,制备了等离子体空心金纳米壳(GNS),其表面覆盖有聚乙二醇化的热敏脂质,作为高效平台来同时递送两种药物,硼替佐米和吉西他滨(GNS-L/GB),用于胰腺癌的联合化疗和光热治疗。硼替佐米被装载在脂质双层内,而吉西他滨则通过硫酸铵驱动的 pH 梯度方法装载到多孔 GNS 的亲水性内部。对 GNS-L/GB 进行了物理化学特性和生物学研究,后者使用细胞毒性测定、细胞摄取和细胞凋亡测定、活/死测定以及胰腺癌细胞系(MIA PaCa-2 和 PANC-1)的 Western blot 分析。当纳米壳暴露于近红外激光下时,可实现远程控制的药物释放,用于特定部位的药物输送。GNS-L/GB 表现出协同细胞毒性,并通过癌细胞的内化得到改善。高功率近红外连续波激光(λ=808nm)通过 GNS-L/GB 的光热效应有效杀死癌细胞,而与细胞类型、功率密度、时间和 GNS 剂量无关。这些结果表明,这种方法可以为实现协同联合化疗和光热治疗提供一种新的途径,甚至对耐药性胰腺癌也有效。
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