Nehate Chetan, Nayal Aradhana, Koul Veena
Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi 110016, India.
Biomedical Engineering Unit, All India Institute of Medical Sciences, New Delhi 110029, India.
ACS Biomater Sci Eng. 2019 Jan 14;5(1):70-80. doi: 10.1021/acsbiomaterials.8b00238. Epub 2018 Oct 19.
In the present investigation, the potential of a novel, self-assembled, biocompatible, and redox-sensitive copolymer system with disulfide bond was explored for doxorubicin (DOX) delivery through polymersome nanostructures of ∼120 nm. The polymer system was synthesized with less steps, providing a high yield of 86%. The developed polymersomes showed admirable biocompatibility with high dose tolerability and . The colloidal stability of DOX-loaded polymersomes depicted a stable and uniform particle size over a period of 72 h. The cellular internalization of polymersomes was assessed in HeLa and MDA-MB-231 cell lines, where enhanced cellular internalization was observed. The dose-dependent cytotoxicity was observed for DOX-loaded polymersomes by MTT cytotoxicity assay in the above cell lines. The tumor suppression studies were assessed in Ehrlich ascites tumor (EAT) carrying Swiss albino mice, where polymersomes exhibited a 7.16-fold reduction in tumor volume correlated with control and 5.39-fold higher tumor inhibition capacity compared to conventional chemotherapy (free DOX treatment). The developed polymersomes gave safer insights concerning DOX associated toxicities by histopathology and serum biochemistry analysis. Thus, results focus on the potential of redox responsive polymersomes for efficacious and improved DOX therapy with enhanced antitumor activity and insignificant cardiotoxicity which can be translated to clinical settings.
在本研究中，探索了一种具有二硫键的新型自组装、生物相容性和氧化还原敏感性共聚物体系通过约120 nm的聚合物囊泡纳米结构递送阿霉素（DOX）的潜力。该聚合物体系合成步骤较少，产率高达86%。所制备的聚合物囊泡表现出令人钦佩的生物相容性和高剂量耐受性。负载DOX的聚合物囊泡的胶体稳定性在72小时内呈现出稳定且均匀的粒径。在HeLa和MDA-MB-231细胞系中评估了聚合物囊泡的细胞内化情况，观察到细胞内化增强。通过MTT细胞毒性试验在上述细胞系中观察到负载DOX的聚合物囊泡具有剂量依赖性细胞毒性。在携带艾氏腹水瘤（EAT）的瑞士白化小鼠中评估了肿瘤抑制研究，聚合物囊泡的肿瘤体积与对照组相比减少了7.16倍，与传统化疗（游离DOX治疗）相比肿瘤抑制能力高5.39倍。通过组织病理学和血清生化分析，所制备的聚合物囊泡在DOX相关毒性方面提供了更安全的见解。因此，结果聚焦于氧化还原响应性聚合物囊泡在有效且改良的DOX治疗中的潜力，具有增强的抗肿瘤活性和微不足道的心脏毒性，有望转化至临床应用。
