Shah Devansh, Bhattacharya Sankha
School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 42540h5, India.
Biomed Mater. 2025 Jul 23;20(4). doi: 10.1088/1748-605X/adefa7.
Poly (ortho esters) (POEs), biodegradable polymers featuring acid-labile ortho ester bonds formed through diol-diketene acetal reactions, are transforming cancer treatment with pH-sensitive surface erosion. This analysis explores the development of POE I, II, III, and IV (POE I-IV), suggesting that their adjustable degradation and controlled drug release may address multidrug resistance (MDR) and transform targeted cancer treatment. We seek to highlight the structural adaptability of POEs, their therapeutic functions, and their potential as advanced drug delivery systems. POE I, developed in the 1970s, faced challenges with autocatalytic degradation. POE II brought in neutral byproducts for enhanced stability, POE III facilitated injectable semi-solid formulations, and POE IV, the ultimate advancement, incorporates latent acid segments for self-catalysed hydrolysis in acidic tumour micro environments (pH 6.5-6.8), removing the need for external excipients. POE nanoparticles (50-300 nm) flexibly modify their size to improve tumour infiltration through the enhanced permeability and retention effect. Surface alterations, such as PEGylation or ligand attachment (e.g. folic acid), enable accurate targeting while minimising systemic toxicity. POEs are proficient in jointly delivering chemotherapeutics and immunomodulators, addressing MDR by inducing apoptosis, necrosis, autophagy, and pyroptosis, enhancing anti-tumour immunity. The degradation products that are biocompatible, such as acids and alcohols, promote immune interaction within the tumour microenvironment (TME). The review examines the synthesis, characterisation, and applications of POEs in post-surgical chemotherapy, ocular oncology, and protein delivery, as well as their interactions with cancer cell membranes and modulation of the TME. Issues such as scalability in manufacturing, enduring biocompatibility, and regulatory challenges are tackled, along with POEs' promise in immunotherapy and gene editing for tailored medicine. Through the integration of these insights, we emphasise POEs as a symbol of optimism for targeted, less harmful cancer therapies, leading to groundbreaking oncology advancements.
聚原酸酯（POEs）是一类可生物降解的聚合物，其具有通过二醇 - 二乙烯酮缩醛反应形成的对酸不稳定的原酸酯键，正通过pH敏感的表面侵蚀改变癌症治疗方式。本分析探讨了聚原酸酯I、II、III和IV（POE I - IV）的发展历程，表明其可调节的降解和可控的药物释放或许能够解决多药耐药性（MDR）问题，并变革靶向癌症治疗。我们旨在突出聚原酸酯的结构适应性、治疗功能及其作为先进药物递送系统的潜力。20世纪70年代开发的POE I面临自催化降解的挑战。POE II产生中性副产物以增强稳定性，POE III促进了可注射半固体制剂的发展，而POE IV作为最终的进展，包含潜在酸性片段以在酸性肿瘤微环境（pH 6.5 - 6.8）中进行自催化水解，无需外部辅料。POE纳米颗粒（50 - 300纳米）可灵活调整其大小，通过增强的渗透和滞留效应改善肿瘤浸润。表面修饰，如聚乙二醇化或配体附着（如叶酸），可实现精准靶向，同时将全身毒性降至最低。POEs擅长联合递送化疗药物和免疫调节剂，通过诱导细胞凋亡、坏死、自噬和焦亡来解决多药耐药性问题，增强抗肿瘤免疫力。具有生物相容性的降解产物，如酸和醇，可促进肿瘤微环境（TME）内的免疫相互作用。本综述研究了聚原酸酯在术后化疗、眼部肿瘤学和蛋白质递送中的合成、表征及应用，以及它们与癌细胞膜的相互作用和对肿瘤微环境的调节。还探讨了制造中的可扩展性、持久的生物相容性和监管挑战等问题，以及聚原酸酯在免疫治疗和基因编辑用于个性化医疗方面的前景。通过整合这些见解，我们强调聚原酸酯是靶向、低伤害癌症治疗乐观前景的象征，将引领肿瘤学取得突破性进展。
