PDF(Pubmed)
Abstract：
Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer (∼0.0014%) reaching tumor cells, limiting the therapeutic efficacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment efficacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fibroblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic efficacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings.
摘要：
纳米颗粒已显示出通过增强的渗透性和保留效应用于肿瘤靶向递送的巨大潜力。然而,肿瘤机械微环境，以致密的细胞外基质（ECM）为特征，高肿瘤硬度和固体应力，导致只有0.7％的给药剂量积累在实体瘤中，甚至更少（〜0.0014％）达到肿瘤细胞，限制纳米颗粒的治疗功效。此外，肿瘤机械微环境可以调节肿瘤细胞的干性，促进肿瘤侵袭，转移和降低治疗疗效。在这次审查中,介绍了机械的检测方法。调节机械微环境的策略，包括通过物理，化学和生物方法，ECM形成的破坏，耗尽或抑制癌症相关的成纤维细胞，然后总结。最后,讨论了机械调节策略的进一步临床应用以增强纳米药物的治疗效果的前景和挑战。本综述可为纳米颗粒的合理设计和临床应用提供指导。
