Hybrid mesoporous silica-based nanocarriers for responsive drug release in cancerous cell line

Abstract

In this work, the synthesis of organic–inorganic hybrids based on pH-responsive, poly(acrylic acid) (PAA) and thermoresponsive, poly(N-isopropyl acrylamide) (PNIPAM), grafted from RAFT agent-primed mesoporous silica nanoparticles (MSNs), has been studied. The confirmation of polymer grafting was obtained through several techniques, for example, FTIR spectroscopy, NMR spectroscopy, etc. The presence of C–H stretching vibrations from FTIR confirmed the presence of organic network in the inorganic MSNs. Further support appeared as notable resonances in 13C solid-state NMR. The resonance at 175 ppm from C=O group for PAA-grafted MSNs, and at 170–172 ppm from C=O group for PNIPAM-grafted MSNs confirmed the grafting of polymer from the RAFT agent-primed MSNs. Morphological analysis for PAA- and PNIPAM-grafted MSNs was performed using FESEM and TEM. The images manifested spherical shape for isobutyric acid group, and short rod shape for phenyl ethyl group-containing RAFT agent-primed MSNs. Subsequently, for assessing their effectiveness as drug delivery vehicle, the anti-cancerous drug doxorubicin hydrochloride (Dox) was loaded into the MSNs. An effective loading in the range of 50–55% in case of PAA-grafted and 49–61% in case of PNIPAM-grafted MSNs (at pH 7.4, 25 °C) was observed. Subsequently release efficiencies for these Dox-encapsulated MSNs were studied at varying pH, temperature and time. The treatment of cultured MCF-7 cell lines by the control MSNs and polymer-grafted MSNs revealed that they are non-toxic. However, when the MSNs were Dox-loaded, the PAA-grafted ones demonstrated higher cytotoxicity than the PNIPAM-grafted MSNs at equivalent dose at pH 7.4 and 37°C. Together with other established features, we show that the polymer-grafted MSNs studied in this work can be utilized as an efficient drug delivery system for different therapeutic applications.