用于靶向药物递送的抗体非共价附着到聚乙二醇化纳米粒子的策略
Strategies for Non-Covalent Attachment of Antibodies to PEGylated Nanoparticles for Targeted Drug Delivery
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影响因子:6.5
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Kai-Wen Ho, Yen-Ling Liu, Tzu-Yi Liao, En-Shuo Liu, Tian-Lu Cheng
DOI:
10.2147/IJN.S479270
摘要
聚乙二醇（PEG）修饰的纳米粒子（NPs）在抗转移和液体肿瘤方面常因细胞摄取和治疗效果有限而效果受限。为此，开发具有增强肿瘤选择性和内吞能力的主动靶向脂质体成为研究热点，以改善摄取率和治疗效果。利用双功能蛋白对PEG修饰纳米粒子进行功能化，从而通过非共价结合方式增强靶向药物递送，已成为一种有潜力的策略。在这些策略中，一步法和两步法靶向策略因其简便、高效和多样性而脱颖而出。一阶段策略将链霉亲和素标记的抗体或双特异抗体（bsAbs：PEG/DIG × 标记）直接整合到PEG修饰纳米粒子中，利用抗体与PEG之间的天然相互作用实现稳定、特异性结合，允许用生物素/抗Fc肽等修饰分子。简单混合bsAbs与PEG修饰的纳米粒子即可改善肿瘤靶向和内吞。二阶段策略则先在肿瘤细胞表面积累bsAbs（PEG/生物素 × 肿瘤标志物），通过抗体依赖和补体依赖的细胞毒作用启动初步攻击，然后这些bsAbs捕获PEG修饰的纳米粒子，触发第二轮内吞和细胞毒性反应。两者均旨在通过识别和结合疾病特异性标志物或受体，增强PEG修饰纳米粒子的靶向能力。本文综述为推动靶向纳米药物研发的临床转化提供了潜在途径。
Abstract
Polyethylene glycol (PEG)-modified nanoparticles (NPs) often struggle with reduced effectiveness against metastasis and liquid tumors due to limited tumor cell uptake and therapeutic efficacy. To address this, actively targeted liposomes with enhanced tumor selectivity and internalization are being developed to improve uptake and treatment outcomes. Using bi-functional proteins to functionalize PEGylated NPs and enhance targeted drug delivery through non-covalent attachment methods has emerged as a promising approach. Among these, the one-step and two-step targeting strategies stand out for their simplicity, efficiency, and versatility. The one-step strategy integrates streptavidin-tagged antibodies or bispecific antibodies (bsAbs: PEG/DIG × marker) directly into PEGylated NPs. This method uses the natural interactions between antibodies and PEG for stable, specific binding, allowing the modification of biotin/Fc-binding molecules like protein A, G, or anti-Fc peptide. Simply mixing bsAbs with PEGylated NPs improves tumor targeting and internalization. The two-step strategy involves first accumulating bsAbs (PEG/biotin × tumor marker) on the tumor cell surface, triggering an initial attack via antibody-dependent and complement-dependent cytotoxicity. These bsAbs then capture PEGylated NPs, initiating a second wave of internalization and cytotoxicity. Both strategies aim to enhance the targeting capabilities of PEGylated NPs by enabling specific recognition and binding to disease-specific markers or receptors. This review provides potential pathways for accelerating clinical translation in the development of targeted nanomedicine.