Construction of hyaluronic acid nanoparticles responsive to breast cancer microenvironment and evaluation of its function in vitro / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare hyaluronic acid(HA)-modified breast cancer microenvironment respond nanoparticles and investigate their physicochemical properties as well as in vitro function. METHODS: The polymer HA-PASP was prepared by linking HA with polyaspartic acid (PASP) through a hydrazone bond. Polyethylene glycol (PEG) was used as contrast material for PEG-PASP. Using Doxorubicin(DOX) as a model drug, HA-PASP-NPs@DOX and PEG-PASP-NPs@DOX were prepared by dialysis method. Particle size, morphology and Zeta potential of nanoparticles were observed by particle size tester and transmission electron microscope (TEM). The physical and chemical properties of nanoparticles were evaluated including encapsulation efficiency, drug loading, stability and drug release ability. In vitro function was evaluated including breast cancer cell targeting and tumor microenvironmental response. RESULTS: HA-PASP-NPs@DOX was spherical and uniform, size was (143±21) nm and Zeta potential was (-27.8±3.8) mV, encapsulation efficiency was 28.3% and drug loading was 5.2%. Under pH 7.4, the structure of nanoparticles was stable for more than 30 d, but under pH 6.5 the drug release up to 96%. HA-PASP-NPs@DOX was targeted to MDA-MB-231 cells, which increased DOX uptake by tumor cells. CONCLUSION: The HA-PASP-NPs@DOX could be successfully prepared by dialysis method, which target breast cancer cells and release drugs efficiently in an acidic environment, what′s more, increase cytotoxicity activity.