Thermo/pH dual-stimuli-responsive drug delivery for chemo-/photothermal therapy monitored by cell imaging

A thermo/pH dual-stimuli-responsive drug delivery system (DDS) based on polymer coated mesoporous silica nanostructures (MSNs) is developed for facilitating chemotherapy and photothermal therapy. Thermo/pH-responsive polymer, poly((N-isopropylacrylamide, NIPAM)-co-methacrylic acid, MA), is grafted onto MSNs by in situ polymerization, followed by loading a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and a near-infrared-absorbing phototherapeutic agent (indocyanine green, ICG) to construct the intelligent drug delivery system, shortly as DOX-ICG-MSN@p(NIPAM-co-MA). At NIR irradiation, the photothermal conversion capability of ICG raises the temperature of the DDS and opens the gatekeeper by shrinkage of the copolymer p(NIPAM-co-MA), which triggers controlled release of DOX at an elevated temperature. On the other hand, drug release is also realized at pH 5.3, a characteristic pH value in cancer cell microenvironment, at which it not only causes the shrinkage of the pH-sensitive polymeric moiety of methacrylic acid in MSN@p(NIPAM-co-MA) but also deteriorates electrostatic interaction of DOX molecules in the mesoporous channel by protonation of silanols. In addition, ICG further ensures photothermal therapy (PTT) and photodynamic therapy (PDT). The cytotoxicity assay of HeLa cells shows obvious synergistic effect by demonstrating that the combined use of DOX and ICG is more effective in killing HeLa cells than free DOX and ICG. The endocytosis of the drug is monitored by cell imaging.