Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science - Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, India; Epigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science - Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, India.
Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science - Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, India.
Int J Pharm. 2021 Sep 5;606:120866. doi: 10.1016/j.ijpharm.2021.120866. Epub 2021 Jul 6.
Delivery of combination chemotherapeutic agents to the tumor via nanovesicles has the potential for superior tumor suppression and reduced toxicity. Herein, we prepare a block copolymer (mPH-RA) composed of methoxy-poly(ethylene glycol) (mPEG), b-poly(N-(2 hydroxypropyl) methacrylamide) (pHPMA), and all-trans retinoic acid (ATRA) by conjugating ATRA to the pre-formed copolymer, mPEG-b-pHPMA(mP-b-pH). Doxorubicin-loaded micelles, Dox@mP-b-pH, and Dox@mPH-RA were characterized by determining particle size, zeta potential, % DL, EE, Dox release, hemolysis study, and by DSC. The Dox@mPH-RA micelles (mPH-RA: Dox ratios of 10:0.5-2) displayed nano-size (36-45 nm), EE. 26-74%, and DL. 2.9-5.6%. Dox@mPH-RA micelles displayed the highest penetrability and cytotoxicity than free Dox and Dox@mP-b-pH micelles in breast cancer cell lines. Dox@mPH-RA exhibited the highest induction of apoptosis (94.1 ± 3%) than Dox (52.1 ± 4.5%), and Dox@mP-b-pH (81.7 ± 3%), and arrested cells in the highest population in G2 and S phase. Dox@mPH-RA increased the t and C of Dox and demonstrated improved therapeutic efficacy and highest Dox distribution to the tumor. The Dox@mPH-RA increased the levels of apoptosis markers, caspase 3, 7, Ki-67, and caused the highest DNA fragmentation. The presence of RA improved the micelles' physicochemical properties, Dox-loading ability, and the therapeutic potential in Dox@mPH-RA via the combination therapeutic strategy.
通过纳米囊泡将联合化疗药物递送到肿瘤部位具有更好的肿瘤抑制作用和降低毒性的潜力。在此，我们通过将全反式维甲酸（ATRA）偶联到预先形成的共聚物甲氧基聚乙二醇（mPEG）-b-聚（N-（2-羟丙基）甲基丙烯酰胺）（pHPMA）（mP-b-pH）上来制备嵌段共聚物（mPH-RA）。阿霉素负载的胶束，Dox@mP-b-pH 和 Dox@mPH-RA 通过测定粒径、Zeta 电位、%DL、EE、Dox 释放、溶血研究和 DSC 进行表征。Dox@mPH-RA 胶束（mPH-RA：Dox 比为 10:0.5-2）显示出纳米尺寸（36-45nm）、EE. 26-74%和 DL. 2.9-5.6%。与游离 Dox 和 Dox@mP-b-pH 胶束相比，Dox@mPH-RA 胶束在乳腺癌细胞系中显示出最高的穿透性和细胞毒性。Dox@mPH-RA 诱导的凋亡率（94.1±3%）高于 Dox（52.1±4.5%）和 Dox@mP-b-pH（81.7±3%），并使细胞停滞在 G2 和 S 期的最高群体中。Dox@mPH-RA 增加了 Dox 的 t 和 C，并显示出改善的治疗效果和最高的 Dox 分布到肿瘤。Dox@mPH-RA 增加了凋亡标志物，半胱天冬酶 3、7、Ki-67 的水平，并导致最高的 DNA 片段化。RA 的存在通过联合治疗策略改善了胶束的物理化学性质、Dox 载药能力和治疗潜力。
