Hollow polypyrrole coated with mesoporous silica nanoparticles graft copolymer multifunctional nanocomposites for intracellular cancer therapy

Abstract A novel hollow polypyrrole coated by mesoporous silica nanoparticles graft poly(2-(4-formylbenzoyloxy)ethyl methacrylate-co-2-(dimethylamino)ethyl methacrylate)-block-poly(triethylene glycol methyl ether methacrylate) multifunctional nanocomposite (HPPy@MSN-SS-NH-g-P(FBEMA-co-DMAEMA)-b-PTEGMA) was designed and prepared via disulfide bond linkages. This material as a gatekeeper integrated multifunctionality such as pore capping, and pH and potothermal multistimuli response abilities, and possessed good photothermal stability, near-infrared (NIR) photothermal conversion capacity and dispersion stability in aqueous solution. It could entrap anticancer doxorubicin (DOX) by pore channels of HPPy@MSN, the core of amphiphilic copolymer micelles and Schiff base linkages, offering a load capacity and load efficiency of up to about 41.5 and 83.1%, respectively. Dynamic light scattering analysis showed that the DOX-loaded preparations had particle size of less than 300 nm, and could achieve intracellular chemo–photothermal combination therapy by controlling the mesopore on-off based on the gatekeepers, tumor environments including pH and reductant stimuli. The drug-loaded nanoparticles exhibited optimal drug release dynamics in cancer tissues upon triggered by pH and glutathione (GSH) under the NIR irradiation. Cell counting Kit-8 assay manifested that the nanocarriers are non-toxic and safe, whereas the drug-loaded preparations exhibited robust anticancer efficacy. Cellular uptake and TUNEL assay revealed high concentrations of DOX accumulating around and inside Hela cells, accordingly producing significant tumor cell apoptosis. Therefore, the newly-developed materials can be used for comprehensive therapy of cancer as a promising candidate of drug delivered carriers.