In Situ Formation of Homogeneous Tellurium Nanodots in Paclitaxel-Loaded MgAl Layered Double Hydroxide Gated Mesoporous Silica Nanoparticles for Synergistic Chemo/PDT/PTT Trimode Combinatorial Therapy.

A folic acid (FA) functional drug delivery system (MT@L-PTX@FA) based on in situ formation of tellurium nanodots (Te NDs) in paclitaxel (PTX)-loaded MgAl layered double hydroxide (LDHs) gated mesoporous silica nanoparticles (MSNs) has been designed and fabricated for targeted chemo/PDT/PTT trimode combinatorial therapy. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), N2 adsorption-desorption, Fourier transform infrared (FT-IR) spectra, and UV-vis spectra were used to demonstrate the successful fabrication of MT@L-PTX@FA. In particular, the in situ generated Te NDs showed a homogeneous ultrasmall size. Reactive oxygen species (ROS) generation, photothermal effects, and photostability evaluations indicated that the in situ generated homogeneous Te NDs could serve as the phototherapeutic agent, converting the photon energy to ROS and heat under near-infrared (NIR) irradiation efficiently. The drug-release test revealed that MT@L-PTX@FA showed an apparent sustained release character in a pH-sensitive manner. In addition, cell imaging experiments demonstrated that MT@L-PTX@FA could selectively enter into cancer cells owing to the function of FA and release of PTX efficiently for chemotherapy for the reason that the low intracellular pH would dissolve MgAl LDHs to Mg2+ and Al3+. Cytotoxicity tests also indicated that MT@L-PTX@FA exhibited enhanced therapeutic effect in cancer cells under NIR irradiation, benefiting from the synergy based on targeted chemo/PDT/PTT trimode combinatorial therapy. The preliminary results reported here will shed new light on the future design and applications of nanosystems for synergistic combinatorial therapy.