Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Nanomedicine. 2024 Oct 1;19:10045-10064. doi: 10.2147/IJN.S479270. eCollection 2024.
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.
聚乙二醇（PEG）修饰的纳米颗粒（NPs）由于肿瘤细胞摄取和治疗效果有限，常常难以有效对抗转移和液体肿瘤。为了解决这个问题，正在开发具有增强肿瘤选择性和内化作用的主动靶向脂质体，以提高摄取和治疗效果。使用双功能蛋白对 PEG 化 NPs 进行功能化，并通过非共价附着方法增强靶向药物输送，已成为一种很有前途的方法。在这些方法中，一步法和两步法靶向策略因其简单性、效率和多功能性而脱颖而出。一步法策略将链霉亲和素标记的抗体或双特异性抗体（PEG/DIG×标记物）直接整合到 PEG 化 NPs 中。这种方法利用抗体和 PEG 之间的天然相互作用进行稳定、特异性结合，允许修饰生物素/Fc 结合分子，如蛋白 A、G 或抗 Fc 肽。只需将 bsAbs 与 PEG 化 NPs 混合即可提高肿瘤靶向性和内化作用。两步法策略涉及首先在肿瘤细胞表面积累 bsAbs（PEG/biotin×肿瘤标记物），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 bsAbs 捕获 PEG 化 NPs，引发第二次内化和细胞毒性。这两种策略都旨在通过使特异性识别和结合疾病特异性标记物或受体，增强 PEG 化 NPs 的靶向能力。这篇综述为靶向纳米医学发展中加速临床转化提供了潜在途径。
