Almoustafa Hassan A, Alshawsh Mohammed Abdullah, Al-Suede Fouad Saleih R, Alshehade Salah Abdulrazak, Abdul Majid Amin Malik Shah, Chik Zamri
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
EMAN Biodiscoveries Sdn. Bhd., A1-4, Lot 5, Persiaran 2/1, Kedah Halal Park, Kawasan Perindustrian Sungai Petani, Sungai Petani 08000, Malaysia.
Polymers (Basel). 2023 Jan 5;15(2):284. doi: 10.3390/polym15020284.
Polyethylene glycol (PEG) coated Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for cancer treatment are biocompatible, nonimmunogenic and accumulate in tumour sites due to the enhanced permeability and retention (EPR). Doxorubicin (DOX) is a potent but cardiotoxic anticancer agent. Hyaluronic acid (HA) occurs naturally in the extra-cellar matrix and binds to CD44 receptors which are overexpressed in cancer metastasis, proven to be characteristic of cancer stem cells and responsible for multidrug resistance. In this study, an athymic mice model of breast cancer metastasis was developed using red fluorescent protein (RFP)-labelled triple negative cancer cells. The animals were divided into four treatment groups (Control, HA-PEG-PLGA nanoparticles, PEG-PLGA nanoparticles, and Free DOX). The tumour size growth was assessed until day 25 when animals were sacrificed. Mice treated with HA-PEG-PLGA NPs inhibited tumour growth. The tumour growth at day 25 (118% ± 13.0) was significantly (p < 0.05) less than PEG-PLGA NPs (376% ± 590 and control (826% ± 970). Fluorescent microscopy revealed that HA-PEG-PLGA NPs had significantly (p < 0.05) less metastasis in liver, spleen, colon, and lungs as compared to control and to Free DOX groups. The efficacy of HA-PEG-PLGA NPs was proven in vivo. Further pharmacokinetic and toxicity studies are required for this formulation to be ready for clinical research.
用于癌症治疗的聚乙二醇(PEG)包覆的聚乳酸-乙醇酸共聚物(PLGA)纳米颗粒(NPs)具有生物相容性、无免疫原性,并且由于增强的通透性和滞留效应(EPR)而在肿瘤部位蓄积。阿霉素(DOX)是一种强效但具有心脏毒性的抗癌药物。透明质酸(HA)天然存在于细胞外基质中,并与CD44受体结合,CD44受体在癌症转移中过度表达,已被证明是癌症干细胞的特征并导致多药耐药。在本研究中,使用红色荧光蛋白(RFP)标记的三阴性癌细胞建立了无胸腺小鼠乳腺癌转移模型。将动物分为四个治疗组(对照组、HA-PEG-PLGA纳米颗粒组、PEG-PLGA纳米颗粒组和游离DOX组)。评估肿瘤大小的生长情况,直至第25天处死动物。用HA-PEG-PLGA NPs治疗的小鼠抑制了肿瘤生长。第25天时的肿瘤生长(118%±13.0)显著(p<0.05)小于PEG-PLGA NPs组(376%±590)和对照组(826%±970)。荧光显微镜检查显示,与对照组和游离DOX组相比,HA-PEG-PLGA NPs在肝脏、脾脏、结肠和肺中的转移显著(p<0.05)减少。HA-PEG-PLGA NPs的疗效在体内得到了证实。该制剂要准备好进行临床研究,还需要进一步的药代动力学和毒性研究。