滨州医学院学报2025，Vol.48Issue(4)：337-343,7.DOI:10.19739/j.cnki.issn1001-9510.2025.04.001
一种具有低氧和弱酸双重响应纳米药物的构建及活性
Construction and activity of a nanomedicine with dual response to hypoxia and weak acidity
摘要
Abstract
Objective To design a weak acid and hypoxia dual response nanodrug TPZ/GOx@CaCO3 to improve its antitu-mor efficacy in response to the characteristics of weak acidity and hypoxia in the tumor microenvironment.Methods A weakly a-cidic and hypoxic dual-responsive nanodrug TPZ/GOx@CaCO3,which encapsulates tirapazamine(TPZ)and glucose oxidase(GOx),was successfully constructed using calcium carbonate(CaCO3)as a carrier by the co-precipitation method.The particle size and zeta potential of TPZ/GOx@CaCO3 were measured with dynamic light scattering(DLS);and the transmission electron microscopy(TEM)was used to observe the morphology under normoxic and hypoxic conditions.The success of the synthesis,as well as the determination of encapsulation efficiency and drug loading capacity,was analyzed and measured through UV-Vis full spectrum scanning.The acid responsiveness of the drug carrier and the dissociation and release profile of the nanomedicine were evaluated by comparing and analyzing the extent of pH change in the solution upon the addition of the nanomedicine under weak acidic,neutral,and weak alkaline conditions,as well as through drug release experiments.The impact of the carrier on the sur-vival rate of L929 cells and the effect of the nanomedicine on the survival rate of 4T1 cells were evaluated through cytotoxicity experiments.The cytotoxic effect was evaluated through live/dead cell staining experiments.Further evaluation of its cytotoxic effect was conducted through apoptosis experiments.Results The nanodrug has a spherical shape with uniform particle size,good morphology,and a drug loading and encapsulation rate that meet the regulatory requirements.Its zeta potential is stably maintained at-10.4 mV.Under weakly acidic conditions,the CaCO3 will dissociate and become irregular,releasing the encap sulated TPZ and GOx.TPZ/GOx@CaCO3 exhibits the highest cytotoxicity,with an IC50 value of 7.2 μg/mL.In the live/dead cell staining experiment,the red fluorescence intensity of TPZ/GOx@CaCO3 is significantly higher than that of GOx@CaCO3 and TPZ@CaCO3,and it induces the highest degree of tumor cell apoptosis.Conclusion The dual-responsive nanomedicine TPZ/GOx@CaCO3,specifically designed for the hypoxic and weakly acidic microenvironment of tumor sites,exhibits excellent antitu-mor activity,providing scientific and technical support for advancements in antitumor therapy.关键词
肿瘤微环境/纳米药物/双重响应/抗肿瘤Key words
tumor microenvironment/nanomedicine/dual response/anti-tumor分类
医药卫生引用本文复制引用
刘钰榕,姜羽轩,陈静..一种具有低氧和弱酸双重响应纳米药物的构建及活性[J].滨州医学院学报,2025,48(4):337-343,7.基金项目
国家自然科学基金(82102209) （82102209）
