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 CaCO3 NPs (DOX@CaCO3/mHA-PEG NPs) for the potential synergistic therapy of breast tumors via Ca2+-induced blood coagulation and drug delivery. This core/shell nanoparticle, with similar to 300 nm in size and-8.6 mV in charge, was composed of 27% of DOX, 65% of CaCO3, and 8% of mHA-PEG in weight percentage. DOX@CaCO3/mHA-PEG NPs were stable in the environment mimicking the bloodstream due to the crosslinked shell with almost no premature delivery of DOX and Ca2+, both of which however were fast released by pH/Hyals stimuli in the mimicking microenvironment of breast cancer cells. The released Ca2+ 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 Ca2+. The released DOX migrated into the cell nucleus for killing cancer cells, while the released Ca2+ moved outside the cells so as to induce tumor vessel coagulation. Herein, DOX@CaCO3/mHA-PEG NPs is a potential candidate for breast cancer synergistic therapy by the com-bination of starvation therapy and chemotherapy.

Automated summary

In this study, a methacrylated hyaluronan-polyethylene glycol (mHA-PEG) decorated and DOX-loaded CaCO3 NPs (DOX@CaCO3/mHA-PEG NPs) were developed for the potential synergistic therapy of breast tumors. The nanoparticles showed stable behavior in the bloodstream and released DOX and Ca2+ in the microenvironment of breast cancer cells. The released DOX killed cancer cells while the released Ca2+ induced tumor vessel coagulation.