Department of Biological Science, Birla Institute of Technology & Science Pilani, Hyderabad Campus, Jawaharnagar, Kapra Mandal, Hyderabad, Telangana 500078, India.
Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, Telangana 500076, India.
Biomed Mater. 2023 Aug 2;18(5). doi: 10.1088/1748-605X/ace8de.
Folate receptor (FR) () has long been the subject of active interest as regards its potential to serve as a target for cancer therapy. FR has been found to be overexpressed in several cancers, including clinical samples of different stages from OSCC (oral squamous cell carcinoma) patients. However, no clear correlation or conclusive finding has been obtained so far which might indicate the efficacy of FR as a credible target for the treatment of OSCC. All cell lines to be used were assessed for FR-expression. Subsequently, we developed glucose-derived carbon nanospheres (CSPs) and primed them with a Folate-based cationic lipid FA8 and the chemotherapeutic drug doxorubicin (DOX). CSP based delivery systems along with pristine drug DOX were characterized and treated subsequently tocultures of OSCC cells and assessed for cancer cell targetability as well as cell death. Subsequently, treatment was administered to immunocompetent C57 mice carrying MOC2 based syngeneic OSCC tumours and assessed for tumour regression and toxicity. Ligand primed targeted CSPs exhibited commendable drug uptake as well as efficient induction of cell death. Further, receptor blocking studies revealed FR-mediated uptake, preferentially in cancer cells. Drug once delivered by ligand-primed CSPs was retained longer inside cells than pristine drug alone, indicating possibilities of better therapeutic outcome. In animal studies, CSP-FA8-DOX (Ligand primed targeted CSP) demonstrated significant regression in tumour size compared to pristine DOX as well as CSP-DOX (non-targeted CSP) treated animals. FR-mediated system CFD demonstrated targeted drug uptake and apoptotic death selectively in cancer cells. Significant tumour regression was also observed. Overall, it may be presumed that the FR is a therapeutic target with substantial potential in OSCC treatment.
叶酸受体 (FR) () 一直是一个活跃的研究对象，因为它有可能成为癌症治疗的靶点。已经发现 FR 在几种癌症中过度表达，包括来自 OSCC（口腔鳞状细胞癌）患者的不同阶段的临床样本。然而，到目前为止，还没有明确的相关性或结论性的发现可以表明 FR 作为 OSCC 治疗的可信靶点的疗效。所有要使用的细胞系都进行了 FR 表达评估。随后，我们开发了葡萄糖衍生的碳纳米球 (CSP)，并用叶酸基阳离子脂质 FA8 和化疗药物阿霉素 (DOX) 对其进行了预处理。CSP 基递药系统与原始药物 DOX 一起进行了表征，并随后用于 OSCC 细胞培养物中，以评估癌细胞靶向性和细胞死亡。随后，在携带基于 MOC2 的同源 OSCC 肿瘤的免疫功能正常的 C57 小鼠中进行了治疗，并评估了肿瘤消退和毒性。配体预处理的靶向 CSP 表现出令人称道的药物摄取以及高效诱导细胞死亡。此外，受体阻断研究表明 FR 介导的摄取，优先在癌细胞中。与单独使用原始药物相比，配体预处理的 CSP 递送的药物在细胞内保留时间更长，这表明可能会有更好的治疗效果。在动物研究中，与单独使用 DOX 以及 CSP-DOX（非靶向 CSP）治疗的动物相比，CSP-FA8-DOX（配体预处理的靶向 CSP）在肿瘤大小方面表现出显著的消退。FR 介导的系统 CFD 选择性地在癌细胞中显示出靶向药物摄取和凋亡死亡。也观察到了显著的肿瘤消退。总体而言，可以假定 FR 是一个具有很大潜力的治疗靶点，在 OSCC 治疗中具有很大的潜力。
