학술논문
肿瘤基质力学特性影响纳米药物递送的研究进展 / Research Progress on the Influence of Tumor Extracellular Matrix Mechanic Properties on Nanodrug Delivery
Document Type
Academic Journal
Author
Source
四川大学学报(医学版) / Journal of Sichuan University(Medical Sciences). 55(1):13-18
Subject
Language
Chinese
ISSN
1672-173X
Abstract
纳米药物广泛应用于生物医学领域,尤其在肿瘤治疗方面表现出巨大的应用潜力.然而肿瘤处于极其复杂的微环境中,在其发展过程中胶原等物质不断沉积和重塑,导致肿瘤发展过程中细胞外基质力学特性发生明显改变.以往研究主要关注纳米药物特定的理化性质,例如粒径、电荷、形状、表面化学性质等对细胞摄取、细胞毒性以及体内药物动力学的影响.鲜有研究关注基质力学特性对纳米药物递送的影响.本综述从肿瘤基质力学的特征、检测方法对该领域的相关研究进行系统的总结,同时也对纳米药物递送过程中可能参与的力学生物学机制进行深入探讨,并提出几个值得重视的研究方向:策略上,重视基质力学-纳米力学的联合靶向递送,实现对药物的精确递送;空间上,重视实体肿瘤内部非线性的空间力学异质性,构建力学微环境适应性纳米载体,以提高递送效率;时间上,重视实体瘤发展、治疗过程中力学微环境动态发展与变化,根据患者个体肿瘤组织的基质力学特性,制定个体化的治疗策略,可以提高治疗的针对性和疗效;此外,可探索动态基质力学环境条件下力学靶向纳米药物递送、降解和代谢等问题.
Nanodrugs are widely utilized in the biomedical fields,exhibiting immense potential in cancer therapy in particular.However,tumors exist in an extremely complicated microenvironment where substances like collagen are continuously deposited and remodeled,leading to significant alterations in the mechanical properties of the extracellular matrix(ECM)during tumor development.Previous research has primarily focused on the specific physicochemical properties of nanodrugs,such as particle size,electric charge,shape,surface chemistry,etc.,and their effects on cellular uptake,cytotoxicity,and in vivo pharmacokinetics.Limited studies have been done to explore the impact of ECM mechanical properties on nanodrug delivery.In this review,we systematically summarized the relevant research findings on this topic from the perspective of the characteristics and testing methods of tumor ECM mechanics.Additionally,we made a thorough discussion of the potential mechanical and biological mechanisms involved in nanodrug delivery.We proposed several noteworthy research directions.Regarding the overall strategy,there is a need to emphasize targeted delivery that combines ECM mechanics and nanomechanics to achieve precise drug delivery.Regarding the spatial aspect,attention should be given to the nonlinear spatial mechanical heterogeneity within the interior of solid tumors and the construction of mechanic microenvironment-adaptive nanocarriers to improve the delivery efficiency.Regarding the temporal aspect,emphasis should be placed on the dynamic development and changes in the mechanical microenvironment during solid tumor growth and treatment processes.Based on the stromal mechanical characteristics of the tumor tissues of individual patients,personalized treatment strategies can be formulated,which will enhance treatment specificity and efficacy.In addition,issues such as mechanically targeted nanodrug delivery,degradation,and metabolism under dynamic ECM mechanical conditions warrant further investigation.
Nanodrugs are widely utilized in the biomedical fields,exhibiting immense potential in cancer therapy in particular.However,tumors exist in an extremely complicated microenvironment where substances like collagen are continuously deposited and remodeled,leading to significant alterations in the mechanical properties of the extracellular matrix(ECM)during tumor development.Previous research has primarily focused on the specific physicochemical properties of nanodrugs,such as particle size,electric charge,shape,surface chemistry,etc.,and their effects on cellular uptake,cytotoxicity,and in vivo pharmacokinetics.Limited studies have been done to explore the impact of ECM mechanical properties on nanodrug delivery.In this review,we systematically summarized the relevant research findings on this topic from the perspective of the characteristics and testing methods of tumor ECM mechanics.Additionally,we made a thorough discussion of the potential mechanical and biological mechanisms involved in nanodrug delivery.We proposed several noteworthy research directions.Regarding the overall strategy,there is a need to emphasize targeted delivery that combines ECM mechanics and nanomechanics to achieve precise drug delivery.Regarding the spatial aspect,attention should be given to the nonlinear spatial mechanical heterogeneity within the interior of solid tumors and the construction of mechanic microenvironment-adaptive nanocarriers to improve the delivery efficiency.Regarding the temporal aspect,emphasis should be placed on the dynamic development and changes in the mechanical microenvironment during solid tumor growth and treatment processes.Based on the stromal mechanical characteristics of the tumor tissues of individual patients,personalized treatment strategies can be formulated,which will enhance treatment specificity and efficacy.In addition,issues such as mechanically targeted nanodrug delivery,degradation,and metabolism under dynamic ECM mechanical conditions warrant further investigation.