Solid SiO2-Sealed Mesoporous Silica for Synergistically Combined Use of Inorganic and Organic Filters to Achieve Safe and Effective Skin Protection from All-Band UV Radiation.

To effectively shield the full band of ultraviolet (UV) radiation and provide desirable protection, the combination of inorganic and organic filters was often used to protect human skin from the serious harm of UV exposure. However, the incompatibility of different filters and their mutual negative effect limit the production of multifilter sunscreen. In addition, the hazard of reactive oxygen species (ROS) produced by inorganic filters after UV exposure and the skin permeability of organic filters remain unresolved problems. In this study, titanium dioxide (TiO2) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), two kinds of common filters with complementary UV shielding range, were first encapsulated into large mesoporous silica nanoparticles (MSN, ∼300 nm) to obtain MSN-TiO2 and MSN-DHHB. Also, a SiO2 coating was then made to seal and stabilize the MSN-TiO2 and MSN-DHHB. The structure, UV screen function, and safety of the SiO2-coated filters, MSN-TiO2@SiO2 and MSN-DHHB@SiO2, were evaluated. The good mechanical stability exhibited by the solid SiO2 layer prevented the release and skin penetration of the sealed DHHB and the photocatalysis of TiO2. Furthermore, the combination of MSN-TiO2@SiO2 and MSN-DHHB@SiO2 in sunscreen cream showed excellent UV shielding performance on covering the whole UV radiation range without mutual interference. Therefore, coating SiO2 over MSN is a feasible strategy for entrapping various filters to improve their photostability, preventing skin penetration and ROS generation, and enhancing their compatibility with different sunscreen formulations.

PolyTLR7/8a-conjugated, antigen-trapping gold nanorods elicit anticancer immunity against abscopal tumors by photothermal therapy-induced in situ vaccination.

Nanovaccine can elicit antigen-specific immune responses against tumor cells expressing homologous antigens and has attracted enormous attention in cancer immunotherapy. However, tumor heterogeneity remarkably hinders the development of nanovaccines. Here we demonstrate that PTT-induced in situ vaccination cancer therapy can elicit potent antitumor immunity against disseminated and metastatic tumors. Gold nanorods (AuNRs) covalently coupled with amphiphilic polyTLR7/8a and MMP-2-sensitive R9-PEG conjugate (AuNRs-IMQD-R9-PEG) were developed as a new biocompatible PTT agent with favorable photothermal efficiency and stability. Importantly, AuNRs-IMQD-R9-PEG can effectively absorb tumor-derived protein antigens, forming nanovaccines directly in vivo and enhance the activation of host dendritic cells (DCs), thereby amplifying adaptive antitumor T-cell responses, triggering effector memory immune responses, and activating innate antitumor immunity. Remarkably, peri-tumoral administration of low-dose multifunctional AuNRs followed by non-invasive near-infrared (NIR) laser irradiation enables efficient tandem PTT-vaccination treatment modality that can inhibit local as well as untreated distant and metastatic tumors in mice inoculated with poorly immunogenic, highly metastatic 4T1 tumors. Our findings indicate that AuNRs-IMQD-R9-PEG-mediated in situ cancer vaccination provides a powerful immunotherapy characterized by markedly increased infiltration of effector CD8+ T, natural killer T (NKT) cells in tumors and long-term animal survival, thus, offering a promising therapeutic strategy for advanced, disseminated cancers.

Thermosensitive injectable hydrogel enhances the antitumor effect of embelin in mouse hepatocellular carcinoma.

Embelin, an active ingredient of traditional herbal medicine, is used to treat many diseases such as cancer. However, embelin is hydrophobic and insoluble in water, which makes it unsuitable for in vivo applications. In this study, we constructed an embelin-loaded thermosensitive injectable hydrogel system that we named Embelin/PECT(gel) based on the amphiphilic triblock copolymer of poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly (ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT). The cytotoxicity and the antitumor effects of Embelin/PECT(gel) on mouse hepatic cancers were investigated in vitro and in vivo. Results indicated that embelin was formulated in PECT hydrogel and could be continuously released from Embelin/PECT(gel) , showing a higher cytotoxicity for H22 cells in vitro compared with free embelin. The aqueous solution of Embelin/PECT(gel) transformed into gel at the injection site within seconds, which later eroded and degraded over time in vivo. A single local peritumoral injection of Embelin/PECT(gel) in liver at a low dosage of 0.5 mg per mouse exhibited a significant antitumor effect, which was comparable to the antitumor effect of the embelin solution treatment at a total dose of 6 mg per mouse in mouse hepatic cancer. Embelin/PECT(gel) , as a drug delivery system in liver, represents a novel therapeutic drug candidate for the clinical treatment of advanced hepatocellular carcinoma.

Graft copolymer nanoparticles with pH and reduction dual-induced disassemblable property for enhanced intracellular curcumin release.

Nanoparticle (NP)-assisted drug delivery systems with disassemblable behaviors in response to intracellular microenvironment are urgently demanded in systemic cancer chemotherapy for enhanced intracellular drug release. Curcumin (CUR), an effective and safe anticancer agent, was limited by its water insolubility and poor bioavailability. Herein, pH and reduction dual-induced disassemblable NPs for high loading efficiency and improved intracellular release of CUR were developed based on an acid degradable cyclic benzylidene acetal groups (CBAs)-functionalized poly(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl)ethane methacrylate)-g-SS-poly(ethylene glycol) (PTTMA-g-SS-PEG) graft copolymer, which was readily prepared via RAFT copolymerization and coupling reaction. The NPs self-assembled from PTTMA-g-SS-PEG copolymers were stable at physiological pH, and quickly disassembled in mildly acidic and reductive environments because of the hydrolysis of CBAs in hydrophobic PTTMA core and the cleavage of disulfide-linked detachable PEG shell. PTTMA-g-SS-PEG NPs exhibited excellent CUR loading capacity with drug loading content up to 19.2% and entrapment efficiency of 96.0%. Within 20 h in vitro, less than 15.0% of CUR was released from the CUR-loaded NPs in normal physiological conditions, whereas 94.3% was released in the presence of reductive agent and mildly acidic conditions analogous to the microenvironment in endosome/lysosome and cytoplasm. Confocal fluorescence microscopies revealed that the CUR-loaded PTTMA-g-SS-PEG NPs exhibited more efficiently intracellular CUR release for EC-109 cells than that of CUR-loaded reduction-unresponsive PTTMA-g-PEG NPs and free CUR. In vitro cytotoxicity studies displayed blank PTTMA-g-SS-PEG NPs showed low toxicity at concentrations up to 1.0 mg/mL, whereas CUR-loaded PTTMA-g-SS-PEG NPs demonstrated more efficient growth inhibition toward EC-109 and HepG-2 cells than reduction-unresponsive controls and free CUR. Therefore, the above results indicated that pH and reduction dual-induced disassemblable PTTMA-g-SS-PEG NPs may have emerged as superior nanocarriers for active loading and promoted intracellular drug delivery in systemic cancer chemotherapy.

Enhanced gene delivery and siRNA silencing by gold nanoparticles coated with charge-reversal polyelectrolyte.

Charge-reversal functional gold nanoparticles first prepared by layer-by-layer technique were employed to deliver small interfering RNA (siRNA) and plasmid DNA into cancer cells. Polyacrylamide gel electrophoresis measurements of siRNA confirmed the occurrence of the charge-reversal property of functional gold nanoparticles. The expression efficiency of enhanced green fluorescent protein (EGFP) was improved by adjuvant transfection with charge-reversal functional gold nanoparticles, which also had much lower toxicity to cell proliferation. Lamin A/C, an important nuclear envelope protein, was effectively silenced by lamin A/C-siRNA delivered by charge-reversal functional gold nanoparticles, whose knockdown efficiency was better than that of commercial Lipofectamine 2000. Confocal laser scanning microscopic images indicated that there was more cy5-siRNA distributed throughout the cytoplasm for cyanine 5-siRNA/polyethyleneimine/cis-aconitic anhydride-functionalized poly(allylamine)/ polyethyleneimine/11-mercaptoundecanoic acid-gold nanoparticle (cy5-siRNA/PEI/PAH-Cit/PEI/MUA-AuNP) complexes. These results demonstrate the feasibility of using charge-reversal functional gold nanoparticles as a means of improving the nucleic acid delivery efficiency.

[Function of nanoparticles in transdermal and transmucosal drug delivery systems].

Nanoparticles had received much attention in the development of new kind of pharmaceutical formation because of the special nano-effectivity. Recently, some studies discovered the special functions of the nanoparticles in transdermal and transmucosal drug delivery systems. Even though the acting mechanism of the nanoparticles in these drug delivery systems are not known, these discoveries of the special function of the nanoparticles provide new developing prospect to the drug delivery systems. This paper mainly reviews the present studying results about the nanoparticles used in the transdermal and transmucosal drug delivery systems, including the lipid nanopaticles, natural polymer and the synthesized polymer nanoparticles.