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功能化壳聚糖用于癌症纳米药物递送。

Functionalized chitosan for cancer nano drug delivery.

机构信息

Non-Destructive Biomedical and Pharmaceutical Research Centre, Smart Manufacturing Research Institute, Universiti Teknologi MARA Selangor, 42300 Puncak Alam, Selangor, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, 42300 Puncak Alam, Selangor, Malaysia.

Non-Destructive Biomedical and Pharmaceutical Research Centre, Smart Manufacturing Research Institute, Universiti Teknologi MARA Selangor, 42300 Puncak Alam, Selangor, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, 42300 Puncak Alam, Selangor, Malaysia; Sino-Malaysia Molecular Oncology and Traditional Chinese Medicine Delivery Joint Research Centre, Medical College, Yangzhou University, 136, Jiangyang Middle Road, Yangzhou, Jiangsu Province, China; Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Biotechnol Adv. 2023 Oct;67:108200. doi: 10.1016/j.biotechadv.2023.108200. Epub 2023 Jun 16.

Abstract

Chitosan is a biotechnological derivative of chitin receiving a widespread pharmaceutical and biomedical applications. It can be used to encapsulate and deliver cancer therapeutics with inherent pH-dependent solubility to confer drug targeting at tumour microenvironment and anti-cancer activity synergizing cancer cytotoxic drug actions. To further reduce the off-target and by-stander adverse effects of drugs, a high targeted drug delivery efficiency at the lowest possible drug doses is clinically required. The chitosan has been functionalized with covalent conjugates or complexes and processed into nanoparticles to encapsulate and control drug release, to avoid premature drug clearance, to deliver drugs passively and actively to cancer site at tissue, cell or subcellular levels, and to promote cancer cell uptake of nanoparticles through membrane permeabilization at higher specificity and scale. Nanomedicine developed using functionalized chitosan translates to significant preclinical improvements. Future challenges related to nanotoxicity, manufacturability, selection precision of conjugates and complexes as a function of cancer omics and their biological responses from administration site to cancer target need critical assessments.

摘要

壳聚糖是甲壳素的生物技术衍生物,在药物和生物医学领域得到了广泛应用。它可以用于封装和输送癌症治疗药物,具有内在的 pH 依赖性溶解度,以实现药物在肿瘤微环境中的靶向作用,并与癌症细胞毒性药物协同发挥抗癌活性。为了进一步降低药物的脱靶和旁观者不良反应,临床上需要以尽可能低的药物剂量实现高靶向药物递送效率。壳聚糖已通过共价轭合物或复合物进行功能化,并加工成纳米颗粒以封装和控制药物释放,以避免药物过早清除,在组织、细胞或亚细胞水平上被动和主动地将药物递送至癌症部位,并通过膜通透性提高纳米颗粒对癌细胞的摄取特异性和规模。使用功能化壳聚糖开发的纳米医学在临床前研究中取得了显著进展。未来的挑战涉及纳米毒性、可制造性、作为癌症组学功能的共轭物和复合物的选择精度,以及它们从给药部位到癌症靶标的生物学反应,需要进行批判性评估。

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