Silica–Calix Hybrid Composite of Allyl Calix[4]arene Covalently Linked to MCM-41 Nanoparticles for Sustained Release of Doxorubicin into Cancer Cells

[Image: see text] An inorganic–organic hybrid material, MCM-allylCalix, was synthesized by covalent modification of an MCM-41 surface with a tetra-allyl calixarene conjugate. The synthesized hybrid was characterized by (13)C and (29)Si MAS–NMR, Fourier transform infrared (FT-IR), Brunauer–Emmett–Teller surface area, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) analyses. The application of this MCM-allylCalix hybrid has been demonstrated for loading and in vitro release of doxorubicin (Dox) in phosphate-buffered saline (PBS) buffer as well as in the cancer cells, viz., MCF7, HeLa, and MDA-MB231. The Dox-loaded hybrid, MCM-allylCalix-Dox, was characterized by TEM, FT-IR, TGA, N(2) sorption, diffuse refectance spectroscopy–UV, and fluorescence microscopy to confirm the presence of the drug. The release study of the drug from MCM-allylCalix-Dox was carried out in PBS buffer at pH 5 and 7.4. The results showed ∼140% increase in the release of Dox at pH 5 compared to that at pH 7.4 in 144 h, suggesting a pH-triggered release of the drug. MCM-allylCalix-Dox releases a greater amount of Dox compared to that released from unmodified MCM-Dox. Cytotoxicity studies suggested that MCM-allylCalix-Dox exhibits anticancer activity that is dependent on the nature of the cell. The Dox-loaded hybrid shows more cytotoxicity for MCF7 compared to that for the HeLa and MDA-MB231 cells. This was further supported by ∼120% more internalization of Dox into MCF7 cells compared to that in the other two cell lines. Both fluorescence microscopy and fluorescence-activated cell sorting studies suggested concentration-dependent internalization of Dox into the MCF7 and HeLa cells. The results suggested that the inorganic–organic hybrid can be useful in sustained drug delivery into cancer cells.