Hyaluronan derivative decorated calcium carbonate nanoparticle as a potential platform for breast cancer synergistic therapy via blood coagulation and drug delivery
Malignant tumor is seriously threatening human lives, and synergistic therapy has recently become a promising strategy. In this study, we developed a methacrylated hyaluronan-polyethylene glycol (mHA-PEG) decorated and DOX-loaded CaCO 3 NPs ( [email protected] 3 /mHA-PEG NPs) for the potential synergistic therapy of breast tumors via Ca 2+ -induced blood coagulation and drug delivery. This core/shell nanoparticle , with ∼300 nm in size and −8.6 mV in charge, was composed of 27% of DOX , 65% of CaCO 3 , and 8% of mHA-PEG in weight percentage. [email protected] 3 /mHA-PEG NPs were stable in the environment mimicking the bloodstream due to the crosslinked shell with almost no premature delivery of DOX and Ca 2+ , both of which however were fast released by pH/Hyals stimuli in the mimicking microenvironment of breast cancer cells. The released Ca 2+ caused fast in vitro blood clotting within 12 min. These nanoparticles were highly internalized by MCF-7 and MDA-MB-231 breast cancer cells, followed by the intracellular release of DOX and Ca 2+ . The released DOX migrated into the cell nucleus for killing cancer cells, while the released Ca 2+ moved outside the cells so as to induce tumor vessel coagulation. Herein, [email protected] 3 /mHA-PEG NPs is a potential candidate for breast cancer synergistic therapy by the combination of starvation therapy and chemotherapy.
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