Gossypol-Capped Mitoxantrone-Loaded Mesoporous SiO₂ NPs for the Cooperative Controlled Release of Two Anti-Cancer Drugs

Mesoporous SiO₂ nanoparticles, MP-SiO₂ NPs, are functionalized with the boronic acid ligand units. The pores of the MP-SiO₂ NPs are loaded with the anticancer drug mitoxantrone, and the pores are capped with the anticancer drug gossypol. The resulting two-drug-functionalized MP-SiO₂ NPs provide a potential stimuli-responsive anticancer drug carrier for cooperative chemotherapeutic treatment. In vitro experiments reveal that the MP-SiO₂ NPs are unlocked under environmental conditions present in cancer cells, e.g., acidic pH and lactic acid overexpressed in cancer cells. The effective unlocking of the capping units under these conditions is attributed to the acidic hydrolysis of the boronate ester capping units and to the cooperative separation of the boronate ester bridges by the lactate ligand. The gossypol-capped mitoxantrone-loaded MP-SiO₂ NPs reveals preferential cytotoxicity toward cancer cells and cooperative chemotherapeutic activities toward the cancer cells. The MCF-10A epithelial breast cells and the malignant MDA-MB-231 breast cancer cells treated with the gossypol-capped mitoxantrone-loaded MP-SiO₂ NPs revealed after a time-interval of 5 days a cell death of ca. 8% and 60%, respectively. Also, the gossypol-capped mitoxantrone-loaded MP-SiO₂ NPs revealed superior cancer-cell death (ca. 60%) as compared to control carriers consisting of β-cyclodextrin-capped mitoxantrone-loaded (ca. 40%) under similar loading of the mitoxantrone drug. The drugs-loaded MP-SiO₂ NPs reveal impressive long-term stabilities.