Ibrahim Muhammad Aiman Irfan, Othman Rozana, Chee Chin Fei, Ahmad Fisol Faisalina
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Centre for Natural Products Research & Drug Discovery (CENAR), Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Biomedicines. 2023 Jul 24;11(7):2080. doi: 10.3390/biomedicines11072080.
Targeting folate receptors is a potential solution to low tumor selectivity concerning conventional chemotherapeutics. Apart from antibody-drug conjugates, folate-functionalized nanoparticle drug delivery systems are interesting to be explored due to many advantages, yet currently, none seems to enter the clinical trials. Multiple in vitro evidence is available to support its efficacy compared to the non-targeting carrier and free drug formulation. Additionally, several studies pointed out factors affecting its effectiveness, including surface properties and endosomal trapping. However, in vivo biodistribution studies revealed issues that may arise from folate receptor targeting, including rapid liver uptake, subsequently reducing the nanoparticles' tumor uptake. This issue may be due to the folate receptor β expressed by the activated macrophages in the liver; route of administration and tumor location might also influence the targeting effectiveness. Moreover, it is perplexing to generalize nanoparticles reported from various publications, primarily due to the different formulations, lack of characterization, and experimental settings, making it harder to determine the accurate factor influencing targeting effectiveness.
针对叶酸受体是解决传统化疗药物肿瘤选择性低这一问题的潜在方法。除了抗体药物偶联物外，叶酸功能化纳米颗粒药物递送系统因其诸多优点而值得探索，但目前似乎尚无进入临床试验的产品。与非靶向载体和游离药物制剂相比，有多项体外证据支持其疗效。此外，多项研究指出了影响其有效性的因素，包括表面性质和内体捕获。然而，体内生物分布研究揭示了叶酸受体靶向可能出现的问题，包括肝脏快速摄取，随后降低纳米颗粒的肿瘤摄取。这个问题可能是由于肝脏中活化巨噬细胞表达的叶酸受体β；给药途径和肿瘤位置也可能影响靶向效果。此外，要对各种出版物报道的纳米颗粒进行概括很困难，主要是因为制剂不同、缺乏表征和实验设置，这使得更难确定影响靶向效果的准确因素。
