Block copolymer-templated mineralization for pH-responsive robust nanocarriers of 5-fluorouracil

We describe a novel synthetic method to prepare calcium carbonate (CaCO₃)-mineralized nanoparticles for the intracellular delivery of an anticancer drug, 5-fluorouracil (5-FU). The 5-FU-loaded mineralized nanoparticles (FU-CaCO₃-MNPs) were prepared by block copolymer (poly(ethylene glycol)-b-poly(L-aspartic acid) (PEG-PAsp))-templated mineralization in the presence of calcium cations (Ca₂₊), carbonate anions (CO₃ ^2-), and negatively charged 5-FU. The mineralization produced hybrid nanoparticles consisting of 5-FU-loaded CaCO ₃ cores and PEG shells. The mineralized CaCO₃ cores of the nanoparticles could stably hold loaded 5-FU by maintaining the structural robustness, and the outer corona of PEG provided colloidal stability to the nanoparticles in serum solutions. The 5-FU release from the FU-CaCO ₃-MNPs at physiological pH (pH 7.4) was efficiently inhibited, whereas at an endosomal pH (pH 5.0), the 5-FU release was facilitated. Fluorescence microscopic analysis showed that FU-CaCO₃-MNPs were taken up by the MCF-7 breast cancer cells, and transferred into acidic endosomes to dissolve the CaCO₃ core. Finally, the 5-FU release was facilitated to inhibit the proliferation of cancer cells. These mineralized hybrid nanoparticles may serve as a useful candidate for enhanced intracellular delivery of many ionic anticancer drugs. [Figure not available: see fulltext.]