Patrojanasophon Prasopchai, Singpanna Kanokwan, Rojanarata Theerasak, Opanasopit Praneet, Ngawhirunpat Tanasait, Pengnam Supusson, Pornpitchanarong Chaiyakarn
Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand; Research and Innovation Center for Advanced Therapy Medicinal Products, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Int J Biol Macromol. 2025 Feb;290:138976. doi: 10.1016/j.ijbiomac.2024.138976. Epub 2024 Dec 20.
This study aimed to develop cisplatin (CDDP)-loaded folic acid (FA)-decorated nanoparticles (NPs) as targeted drug carrier towards overexpressed folate receptors on the oral carcinoma cell line (KB cells). The FA-conjugated thiolated succinyl chitosan (FA-SH-SCS) and maleimide-grafted-carboxymethyl cellulose (CMC-MAL) were synthesized and acquired in the preparation of NPs via thiol-maleimide click reaction. The physicochemical characteristics, drug loading, and drug release of the FA-decorated NPs (FA-NPs) were examined. Also, the in vitro biocompatibility, cellular uptake, and cell death mechanism were investigated. Relatively spherical NPs with negative charge were obtained with a size of approximately 200 nm. The formation of FA-NPs through click reaction was confirmed by the pH change and Ellman's assay. The release of CDDP from the FA-NPs was influenced by the acidic tumor environment. The FA-NPs were non-toxic to the normal cells. Furthermore, FA-NPs improved the cellular uptake of CDDP in oral carcinoma cells through specific recognition of folate receptors by FA-NPs. The delivery of CDDP by FA-NPs to the KB cell induced the apoptotic cell death pathway. Therefore, FA-NPs presented the potential to be effective nanocarriers for CDDP delivery in the treatment of oral cancer via active targeting approach.
本研究旨在开发负载顺铂（CDDP）的叶酸（FA）修饰纳米颗粒（NPs），作为针对口腔癌细胞系（KB细胞）上过表达叶酸受体的靶向药物载体。合成了叶酸共轭硫醇化琥珀酰壳聚糖（FA-SH-SCS）和马来酰亚胺接枝羧甲基纤维素（CMC-MAL），并通过硫醇-马来酰亚胺点击反应用于制备纳米颗粒。研究了FA修饰纳米颗粒（FA-NPs）的理化特性、载药量和药物释放情况。此外，还研究了其体外生物相容性、细胞摄取和细胞死亡机制。获得了相对呈球形且带负电荷的纳米颗粒，尺寸约为200nm。通过pH变化和埃尔曼测定法证实了通过点击反应形成了FA-NPs。FA-NPs中CDDP的释放受酸性肿瘤环境影响。FA-NPs对正常细胞无毒。此外，FA-NPs通过FA-NPs对叶酸受体的特异性识别提高了口腔癌细胞中CDDP的细胞摄取。FA-NPs将CDDP递送至KB细胞诱导了凋亡细胞死亡途径。因此，FA-NPs有潜力成为通过主动靶向方法在口腔癌治疗中有效递送CDDP的纳米载体。
