TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

Additive Manufacturing for Terahertz Metamaterials on the Dielectric Surface based on Optimized Electrohydrodynamic Drop-on-demand Printing Technology.

The conventional techniques used to fabricate terahertz metamaterials, such as photolithography and etching, face hindrances in the form of high costs, lengthy processing cycles, and environmental pollution. In contrast, electrohydrodynamic (EHD) drop-on-demand (DOD) printing technology holds promise as an additive manufacturing method capable of producing micrometer- and nanometer-scale patterns rapidly and cost-effectively. However, achieving stable large-area printing proves challenging due to issues related to charge accumulation in insulated substrates and inconsistent meniscus vibration. In this paper, a smooth bipolar waveform driving method is proposed aimed at solving the problems of charge accumulation on insulated substrates and poor print consistency. The method involves utilizing driving waveforms with opposite polarities for neighboring droplets, allowing the charges carried by the printed droplets to neutralize each other. Moreover, extending the duration of the high voltage rise and fall times enhances the consistency of meniscus motion, thereby improving the stability of printing. Through optimization of the printing parameters, droplets with a diameter of 1.37 µm and straight lines with a width of 3 µm were printed. Furthermore, this approach was employed to print terahertz metamaterial surface devices, and the performance of the metamaterial is in good agreement with the simulation results. These findings demonstrate that the method greatly improves the stability of EHD DOD printing, thereby advancing the application of the technology in additive processing at the micro- and nanoscale.

Self-controlled release of Oxaliplatin prodrug from d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) functionalized mesoporous silica nanoparticles for cancer therapy.

Oxaliplatin is a promising antitumor drug, but its effectiveness is limited by its side effects in vivo. In this study, we introduced an Oxaliplatin prodrug (Oxa(IV)) self-controlled release strategy, in which Oxa(IV) is encapsulated by TPGS functionalized mesoporous silica nanoparticles (MSNs), and its release is controlled by biological stimuli, such as acidic environments in tumor tissue and high concentrations of reductants in cancer cells. Despite the lack of auxiliary "gatekeepers" to MSNs, this simplified model of Oxa(IV)-MSNs-TPGS could fine-tune the movements of the drug release. Furthermore, we utilized a prodrug approach to avoid the side effects of Oxaliplatin, and we used TPGS groups to reduce multidrug resistance (MDR). Finally, the toxicity of Oxa(IV)-MSNs-TPGS to a human lung adenocarcinoma cell line (A549) in vitro was significantly lower than that of Oxaliplatin. This model demonstrates the considerable potential of a simple self-controlled release system with multiple functions.

A multifunctional nanoplatform for cancer chemo-photothermal synergistic therapy and overcoming multidrug resistance.

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.

pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy.

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, N2 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.

Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects.

Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH2-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH2-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.

A drug-self-gated and tumor microenvironment-responsive mesoporous silica vehicle: "four-in-one" versatile nanomedicine for targeted multidrug-resistant 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.