In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX-loaded NPs without the folic targeting ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying that they are a highly promising potential carrier for cancer treatments.
The integration of various therapy strategies into a single nanoplatform for synergistic cancer treatment has presented a great prospect. Herein, docetaxel (DTX)-loaded poly lactic-co-glycolic acid (PLGA)-coated polydopamine modified with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was synthesized for chemo-photothermal synergistic therapy against cancer. Firstly, the DTX-loaded PLGA NPs were prepared by a facile and robust nanoprecipitation method. Then, they were coated with dopamine to achieve the photothermal effects and to be further modified with TPGS, which can inhibit the P-glycoprotein-mediated multidrug resistance (MDR). The near-infrared (NIR) laser irradiation triggered DTX release from DTX-loaded PLGA NPs@PDA-TPGS, and then the chemo-photothermal therapy effect could be enhanced. The in vitro experimental results illustrated that DTX-loaded PLGA NPs@PDA-TPGS exhibits excellent photothermal conservation properties and remarkable cell-killing efficiency. In vivo antitumor studies further confirmed that DTX-loaded PLGA NPs@PDA-TPGS could present an outstanding synergistic antitumor efficacy compared with any monotherapy. This work exhibits a novel nanoplatform, which could not only load chemotherapy drugs efficiently, but could also improve the therapeutic effect of chemotherapy drugs by overcoming MDR and light-mediated photothermal cancer therapy.
The design of multifunctional nanocarriers for the co-delivery of anticancer drugs and genetic agents offers an effective and promising strategy to combat multidrug-resistant cancer. Herein, we developed a simple and facile method to fabricate a drug-self-gated and pH-sensitive mesoporous silica vehicle as a "four-in-one" versatile co-delivery system, which possesses targeted chemo and gene therapy capability against multidrug-resistant cancer. P-gp siRNA molecules were loaded into the channels of mesoporous silica nanoparticles. A chemotherapeutic drug (DOX) was employed as a gatekeeper via a pH-sensitive benzoic-imine covalent bond. Folic acid conjugation onto the surface endowed this system with an excellent tumor-targeting effect, which was demonstrated by the cellular and tumor targeting assay. The effective downregulation of P-gp protein by the co-delivered P-gp siRNA was observed by western blotting. Both the in vitro cell viability study and in vivo tumor inhibition assay showed a synergistic effect in suppressing cancer cell proliferation. Therefore, this drug-self-gated nanosystem exhibited great potential for improved multidrug-resistant cancer treatment without any further potential risks of capping agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.