Mannosylated poly(acrylic acid)-coated mesoporous silica nanoparticles for anticancer therapy

• DOI: 10.1016/j.jconrel.2022.06.064
• Publication Date: 2022-07-09T00:02:44Z
• Authors: Haesoo Lee; Miseop Choi; Ha-Eun Kim; Minki Jin; Woo-Jin Jeon; Minwoo Jung; Hyelim Yoo; Jong-Hee Won; Young-Guk Na; Jae-Young Lee; Hasoo Seong; Hong-Ki Lee; Cheong-Weon Cho
• Keywords: Drug Carriers; Polymers; Acrylic Resins; Antineoplastic Agents; Hydrogen-Ion Concentration; Silicon Dioxide; 01 natural sciences; 0104 chemical sciences; 3. Good health; Drug Liberation; Mice; Drug Delivery Systems; Doxorubicin; Animals; Humans; Nanoparticles; Reactive Oxygen Species; Mannose; Porosity

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.