Polylactic acid based polymeric nanoparticle mediated co-delivery of navitoclax and decitabine for cancer therapy

IF 4.7 4区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-01-01 DOI:10.1016/j.nano.2022.102627

Neha Mehrotra PhD , Mohd Anees M.Sc , Sachchidanand Tiwari M.Tech , Surender Kharbanda PhD , Harpal Singh PhD

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引用次数: 2

Abstract

Combination chemotherapy with systemic administration of drugs in their free form can be challenging due to non-synchronized pharmacokinetics and sub-optimal tumor accumulation. The present study investigates a PLA-based block copolymeric nanocarrier for the co-delivery of navitoclax and decitabine (NAV/DCB NPs) for combination cancer therapy. NAV/DCB NPs exhibited potent in vitro synergistic cytotoxicity in both acute myeloid leukemia and breast cancer cell lines. Biodistribution studies of NAV/DCB NPs in tumor bearing mice, showed significant drug accumulation in tumor tissue and detectable quantities in plasma even after 48 h. Good hemocompatibility with reduced in vivo platelet toxicity indicated that encapsulation in PLA-based nanocarrier helped ameliorate navitoclax associated thrombocytopenia. In vivo biological activity of NAV/DCB NPs evaluated in xenograft AML and syngeneic breast cancer model, demonstrated potent tumor growth inhibition efficacy. PLA-based NAV/DCB dual NPs present a novel, safe and effective nanoformulation for combination cancer therapy in both solid tumors and hematologic malignancies.

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聚乳酸基聚合物纳米颗粒介导的纳维托克拉克和地西他滨共同递送用于癌症治疗

由于非同步的药代动力学和次优的肿瘤积累，联合化疗与全身自由形式的药物管理可能具有挑战性。本研究研究了一种基于pla的嵌段共聚物纳米载体，用于联合递送navitoclax和地西他滨(NAV/DCB NPs)用于联合癌症治疗。NAV/DCB NPs在急性髓性白血病和乳腺癌细胞系中均表现出强大的体外协同细胞毒性。NAV/DCB NPs在荷瘤小鼠体内的生物分布研究显示，即使在48小时后，NAV/DCB NPs在肿瘤组织中也有明显的药物积累，血浆中也有可检测到的药物量。良好的血液相容性和体内血小板毒性降低表明，pla纳米载体的包封有助于改善navitoclax相关的血小板减少。NAV/DCB NPs的体内生物活性在异种移植物AML和同基因乳腺癌模型中被评估，显示出强大的肿瘤生长抑制作用。基于pla的NAV/DCB双NPs为实体瘤和血液系统恶性肿瘤的联合治疗提供了一种新的、安全有效的纳米制剂。

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来源期刊

Nanomedicine: Nanotechnology, Biology and Medicine 医学-纳米科技

CiteScore

8.10

自引率

3.60%

发文量

104

审稿时长

4.6 months

期刊介绍： Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.