Abstract:
Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.
摘要:
纳米技术的最新发展为癌症的诊断和治疗带来了新的方法。虽然增强的渗透性和保留作用促进了纳米化疗剂的外渗,异常的肿瘤脉管系统,高的间质压力和致密的间质结构限制了纳米化疗药物的均匀瘤内分布,并损害了其成像和治疗效果。此外,纳米化学疗法在非肿瘤基质细胞中的异质分布会损害非肿瘤细胞,并干扰肿瘤-基质串扰。这不仅可以抑制肿瘤进展,但也可以矛盾地诱导获得性耐药,促进肿瘤细胞增殖和转移。总的来说,肿瘤微环境对纳米化疗药物的分布及其生物学效应具有重要的调节作用。在这次审查中,肿瘤微环境中的屏障,它对纳米化学疗法的影响,总结了改善纳米化疗药物递送的考虑因素和克服肿瘤微环境诱导的获得性耐药的组合策略。各种策略。,基于纳米技术的方法以及配体介导的方法,氧化还原响应,本文讨论了基于酶介导的组合纳米方法。