非共价附着在靶向药物递送的抗体纳米颗粒的抗体附着的策略
Strategies for Non-Covalent Attachment of Antibodies to PEGylated Nanoparticles for Targeted Drug Delivery
影响因子:6.50000
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
摘要
聚乙烯乙二醇（PEG）修饰的纳米颗粒（NPS）通常因肿瘤细胞摄取和治疗功效而导致的转移和液体肿瘤的有效性降低。为了解决这个问题，正在开发具有增强肿瘤选择性和内在化的积极靶向脂质体，以改善摄取和治疗结果。使用双官能蛋白来使卵巢NP官能化并通过非共价附着方法增强靶向药物递送，这已成为一种有希望的方法。其中，一步和两步的定位策略在简单，效率和多功能性方面脱颖而出。单步策略将链霉亲和素标记的抗体或双特异性抗体（BSABS：PEG/DIG×Marker）直接集成到Pegymet NP中。该方法使用抗体与PEG之间的自然相互作用进行稳定，特异性结合，从而使生物素/FC结合分子（如蛋白A，G或抗FC肽）进行了修饰。简单地将BSAB与二乙二醇的NP混合可以改善肿瘤的靶向和内在化。两步策略涉及在肿瘤细胞表面上首先积累BSAB（PEG/Biotin×肿瘤标记），从而通过抗体依赖性和补体依赖性细胞毒性引发初始攻击。然后，这些BSAB捕获了卵子的NP，引发了第二波的内在化和细胞毒性。两种策略旨在通过实现特定识别并与疾病特异性标记或受体结合来增强质量NP的靶向能力。这篇综述为靶向纳米医学的发展提供了加速临床翻译的潜在途径。
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.