Rouhani Hasti, Sepehri Nima, Montazeri Hamed, Khoshayand Mohammad Reza, Ghahremani Mohammad Hossein, Ostad Seyed Nasser, Atyabi Fatemeh, Dinarvand Rassoul
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Pharm Res. 2014 Aug;31(8):2124-39. doi: 10.1007/s11095-014-1313-7. Epub 2014 Feb 21.
Oxidation therapy is an antitumor strategy in which, apoptosis or necrosis is caused by either excess delivery of reactive oxygen species (ROS) as an oxidant or anti-oxidant inhibition. Heme oxygenase (HO) is an anti-oxidant enzyme that plays an important role in cell growth and proliferation. The purpose of this study was to prepare poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with zinc protoporphyrin (ZnPP) to deliver the HO inhibitor into tumor.
PLGA NPs were prepared using nanoprecipitation technique and their characteristics were optimized by Box-Behnken experimental design. Scanning electron microscopy and in vitro studies consisting of drug release, HO inhibitory effect, cytotoxicity and cellular uptake followed by in vivo biodistribution and blood cytotoxicity were carried out. Internalization of coumerin-6 loaded NPs by PC3 cells was visualized by confocal laser scanning microscopy beside quantitatively analysis.
NPs average size, entrapment efficiency and drug loading were 100.12 ± 5.345 nm, 55.6% ± 2.49 and 7.98% ± 0.341 respectively. Equal HO inhibitory effect of NPs compared to free ZnPP was observed. The IC50 value of ZnPP-NPs for PC3 human prostate cancer cells was found to be 2.14 ± 0.083 μM.
In conclusion, ZnPP loaded PLGA NPs could exhibit enough HO inhibitory effect against cancer cells to be considered as a promising candidate for cancer treatment investigation.
氧化疗法是一种抗肿瘤策略，通过作为氧化剂的活性氧（ROS）过量递送或抗氧化抑制来引发细胞凋亡或坏死。血红素加氧酶（HO）是一种抗氧化酶，在细胞生长和增殖中起重要作用。本研究的目的是制备负载锌原卟啉（ZnPP）的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NPs），以便将HO抑制剂递送至肿瘤部位。
采用纳米沉淀技术制备PLGA NPs，并通过Box-Behnken实验设计优化其特性。进行扫描电子显微镜观察以及包括药物释放、HO抑制作用、细胞毒性和细胞摄取的体外研究，随后进行体内生物分布和血液细胞毒性研究。通过共聚焦激光扫描显微镜对PC3细胞摄取香豆素-6负载的NPs进行可视化观察，并进行定量分析。
NPs的平均粒径、包封率和载药量分别为100.12±5.345nm、55.6%±2.49和7.98%±0.341。观察到NPs与游离ZnPP具有同等的HO抑制作用。发现ZnPP-NPs对PC3人前列腺癌细胞的IC50值为2.14±0.083μM。
总之，负载ZnPP的PLGA NPs对癌细胞可表现出足够的HO抑制作用，有望成为癌症治疗研究的候选药物。
