Gagneja Simran, Capalash Neena, Sharma Prince
Department of Microbiology, Panjab University, Chandigarh, India.
Department of Biotechnology, Panjab University, Chandigarh, India.
Int J Biol Macromol. 2024 Aug;275(Pt 2):133744. doi: 10.1016/j.ijbiomac.2024.133744. Epub 2024 Jul 8.
Hyaluronic acid is a major constituent of the extracellular matrix of vertebrate tissue that provides mechanical support to cells and acts as a mediator in regulation of necessary biochemical process essential for maintenance of tissue homeostasis. The variation in quantity of hyaluronic acid content in tissues is often associated with different pathological conditions. It is associated with tumor aggression and progression as it plays crucial role in regulating different aspects of tumorigenesis and several defined hallmarks of cancer. It assists in tumor progression by undergoing extracellular remodeling to establish tumor microenvironment which restricts the delivery of cytotoxic drugs to neoplastic cells due to increase in interstitial pressure. Hyaluronic acid catabolic and anabolic genes and low-molecular weight hyaluronic acid play significant role in the establishing tumor microenvironment by assisting in cell proliferation, metastasis and invasion. On the other hand, it is also used as an effective drug-delivery platform in cancer therapies as its biocompatibility and biodegradability lower the toxicity of chemotherapeutic drugs and increase drug retention. High-molecular weight hyaluronic acid-bioconjugates specifically bind with hyaladherins, facilitating targeted drug delivery and also exert anti-inflammatory properties. This review also highlights the market and patent trends in the development of effective chemotherapeutic hyaluronic acid formulations and the current scenario regarding clinical trials.
透明质酸是脊椎动物组织细胞外基质的主要成分,为细胞提供机械支持,并在调节维持组织稳态所必需的生化过程中起介质作用。组织中透明质酸含量的变化通常与不同的病理状况相关。它与肿瘤侵袭和进展相关,因为它在调节肿瘤发生的不同方面以及癌症的几个明确特征中起着关键作用。它通过进行细胞外重塑来建立肿瘤微环境,从而促进肿瘤进展,由于间质压力增加,这种微环境会限制细胞毒性药物向肿瘤细胞的递送。透明质酸分解代谢和合成代谢基因以及低分子量透明质酸通过协助细胞增殖、转移和侵袭,在建立肿瘤微环境中发挥重要作用。另一方面,它还因其生物相容性和可生物降解性降低了化疗药物的毒性并增加了药物滞留时间,而被用作癌症治疗中的有效药物递送平台。高分子量透明质酸生物共轭物与透明质酸黏附素特异性结合,促进靶向药物递送并发挥抗炎特性。本综述还强调了有效化疗透明质酸制剂开发中的市场和专利趋势以及当前临床试验的情况。