Chitosan nanoparticles (NPs) are well-recognized as promising vehicles for delivering anticancer drugs due to their distinctive characteristics. They have the potential to enclose hydrophobic anticancer molecules, thereby enhancing their solubilities, permeabilities, and bioavailabilities; without the use of surfactant, i.e., through surfactant-free solubilization. This allows for higher drug concentrations at the tumor sites, prevents excessive toxicity imparted by surfactants, and could circumvent drug resistance. Moreover, biomedical engineers and formulation scientists can also fabricate chitosan NPs to slowly release anticancer agents. This keeps the drugs at the tumor site longer, makes therapy more effective, and lowers the frequency of dosing. Notably, some types of cancer cells (fallopian tube, epithelial tumors of the ovary, and primary peritoneum; lung, kidney, ependymal brain, uterus, breast, colon, and malignant pleural mesothelioma) have overexpression of folate receptors (FRs) on their outer surface, which lets folate-drug conjugate–incorporated NPs to target and kill them more effectively. Strikingly, there is evidence suggesting that the excessively produced FR&αgr (isoforms of the FR) stays consistent throughout treatment in ovarian and endometrial cancer, indicating resistance to conventional treatment; and in this regard, folate-anchored chitosan NPs can overcome it and improve the therapeutic outcomes. Interestingly, overly expressed FRs are present only in certain tumor types, which makes them a promising biomarker for predicting the effectiveness of FR-targeted therapy. On the other hand, the folate-modified chitosan NPs can also enhance the oral absorption of medicines, especially anticancer drugs, and pave the way for effective and long-term low-dose oral metronomic scheduling of poorly soluble and permeable drugs. In this review, we talked briefly about the techniques used to create, characterize, and tailor chitosan-based NPs; and delved deeper into the potential applications of folate-engineered chitosan NPs in treating various cancer types. Schematic illustration of target ligand-drug incorporated chitosan nanoparticles and its advantage in treating cancer. Figure created with BioRender.Com.

中文翻译：

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叶酸工程壳聚糖纳米颗粒：下一代抗癌纳米载体


壳聚糖纳米颗粒 （NPs） 因其独特的特性而被公认为是有前途的抗癌药物递送载体。它们有可能包围疏水性抗癌分子，从而提高它们的溶解度、渗透性和生物利用度;无需使用表面活性剂，即通过不含表面活性剂的增溶。这允许肿瘤部位的药物浓度更高，防止表面活性剂赋予的过度毒性，并且可以规避耐药性。此外，生物医学工程师和配方科学家还可以制造壳聚糖 NP 以缓慢释放抗癌剂。这样可以使药物在肿瘤部位停留更长时间，使治疗更有效，并降低给药频率。值得注意的是，某些类型的癌细胞（输卵管、卵巢上皮肿瘤和原发性腹膜;肺、肾、室管膜脑、子宫、乳腺癌、结肠和恶性胸膜间皮瘤）在其外表面过表达叶酸受体 （FR），这使得叶酸药物偶联物掺入的 NP 可以更有效地靶向和杀死它们。引人注目的是，有证据表明，在卵巢癌和子宫内膜癌的整个治疗过程中，过量产生的 FR&αgr（FR 的亚型）保持一致，表明对常规治疗的耐药性;在这方面，叶酸锚定的壳聚糖 NPs 可以克服它并改善治疗效果。有趣的是，过表达的 FRs 仅存在于某些肿瘤类型中，这使它们成为预测 FR 靶向治疗效果的有前途的生物标志物。 另一方面，叶酸改性壳聚糖 NPs 还可以增强药物，尤其是抗癌药物的口服吸收，为难溶性和渗透性药物的有效和长期低剂量口服节律调度铺平了道路。在这篇综述中，我们简要讨论了用于创建、表征和定制基于壳聚糖的 NP 的技术;并深入研究了叶酸工程壳聚糖 NP 在治疗各种癌症类型中的潜在应用。掺入壳聚糖纳米颗粒的靶配体药物及其在治疗癌症中的优势的示意图。使用 BioRender.Com 创建的图窗。