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转铁蛋白导向脂质体纳米载体:一种靶向癌症治疗的策略。

Transferrin-guided liposomal nanocarriers: A strategy for targeted cancer treatment.

作者信息

Saeed Mohd, Altamash Mohd, Almoyad Mohammad Ali Abdullah, Wahab Shadma, Gupta Garima, Goh Khang Wen, Kesharwani Prashant

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.

Department of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Khamis Mushyt, PO Box. 4536, ZIP 61412, Saudi Arabia.

出版信息

Int J Biol Macromol. 2025 Jun 20;319(Pt 3):145377. doi: 10.1016/j.ijbiomac.2025.145377.

Abstract

Cancer, characterized by uncontrolled cell proliferation and aberrant vascularization, remains a major challenge in clinical therapeutics. While chemotherapy is a cornerstone of cancer treatment, its effectiveness is often limited by systemic toxicity and lack of tissue specificity, which constrain the achievable therapeutic doses. When compared to traditional formulations, targeted drug delivery systems employing nanoparticles have demonstrated up to ten times greater bioavailability and three to five times higher drug accumulation in tumor tissues. Nanoparticles (NPs) offer versatile and customizable platforms that improve the solubility, permeability, and bioavailability of therapeutic agents. In addition, NPs exhibit favorable pharmacokinetic properties, enable sustained and controlled drug release, and allow selective targeting of specific cells, tissues, or organs-collectively enhancing the therapeutic efficacy of conventional drugs. Also, by lowering systemic toxicity, nanocarriers enable 50-70 % dosage reductions in chemotherapeutic drugs without sacrificing effectiveness. This review highlights recent advances in nanotechnology-driven strategies to overcome these limitations, with a particular focus on transferrin (Tf) receptor-mediated targeting. It begins by discussing the biological rationale for Tf-targeted drug delivery and the advantages of liposomal formulations in oncology, particularly describing their use in treating brain cancer, liver cancer, lung cancer, ovarian cancer, breast cancer, bone cancer, gastric cancer, and prostate cancer. Subsequently, it explores various methods for the preparation of Tf-engineered liposomes, ranging from conventional techniques to advanced drug encapsulation strategies to solve the problems that arises when transferrin is used alone like BBB penetration, Drug resistance. Finally, the review provides a comprehensive analysis of preclinical and clinical studies evaluating the efficacy and safety of Tf-functionalized liposomes in cancer therapy.

摘要

癌症以细胞不受控制的增殖和异常血管化为特征,仍然是临床治疗中的一项重大挑战。虽然化疗是癌症治疗的基石,但其有效性常常受到全身毒性和缺乏组织特异性的限制,这限制了可达到的治疗剂量。与传统制剂相比,采用纳米颗粒的靶向药物递送系统已显示出生物利用度提高多达十倍,肿瘤组织中的药物蓄积量提高三到五倍。纳米颗粒(NPs)提供了多功能且可定制的平台,可改善治疗剂的溶解度、渗透性和生物利用度。此外,纳米颗粒具有良好的药代动力学特性,能够实现药物的持续和可控释放,并允许对特定细胞、组织或器官进行选择性靶向,从而共同提高传统药物的治疗效果。而且,通过降低全身毒性,纳米载体能够在不牺牲疗效的情况下将化疗药物的剂量降低50%至70%。本综述重点介绍了纳米技术驱动的策略在克服这些局限性方面的最新进展,特别关注转铁蛋白(Tf)受体介导的靶向作用。首先讨论了Tf靶向药物递送的生物学原理以及脂质体制剂在肿瘤学中的优势,尤其描述了它们在治疗脑癌、肝癌、肺癌、卵巢癌、乳腺癌、骨癌、胃癌和前列腺癌中的应用。随后,探讨了制备Tf工程化脂质体的各种方法,从传统技术到先进的药物封装策略,以解决单独使用转铁蛋白时出现的问题,如血脑屏障穿透、耐药性。最后,本综述对评估Tf功能化脂质体在癌症治疗中的疗效和安全性的临床前和临床研究进行了全面分析。

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