Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200 nm in the neutral pH and 60 nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Gold Nanorods/Polypyrrole/m-SiO2 Core/Shell Hybrids as Drug Nanocarriers for Efficient Chemo-Photothermal Therapy.

Combination therapy as a novel strategy with the combination of photothermal therapy and chemotherapy (photothermal-chemotherapy) has aroused the tremendously increasing interest owing to the synergistic therapeutic effect on destroying cancer cells because the hyperthermia generated from photothermal therapy can promote drug delivery into tumors, which would highly increase therapeutic efficacy as compared to those sole treatments. Herein, we fabricated a novel nanomaterial-based carrier composed of gold nanorods (GNRs), polypyrrole (PPy), and mesoporous silica to form GNRs/PPy/m-SiO2 core/shell hybrids. After loading the anticancer drug of doxorubicin (DOX), the photothermal effect and the drug-release behavior of GNRs/PPy@m-SiO2-DOX hybrids were investigated. The in vitro and in vivo near-infrared (NIR) photothermal-chemotherapy were also revealed. The results indicated that the NIR-induced photothermal effect was beneficial to promote the release of the drug. In addition, combination therapy demonstrated the enhanced synergistic efficacy and excellent treatment efficacy for cancer therapy.

Building covalent crosslinks of carboxymethyl konjac glucomannan with boronic ester bonds for fabricating multimodal hydrogel sensor.

As the derivative of konjac glucomannan (KGM), carboxymethyl konjac glucomannan (CMK) has attracted increasing attention in the polysaccharide hydrogel fields with the aim of improving the performance related to drug delivery and release. In this study, we prepared a CMK-based hydrogel with dual characteristic crosslinks, and unlocked new applications of this type of hydrogel in soft sensor fields. CMK and poly (vinyl alcohol) were used as substrates, and physical crosslinks were constructed via the freeze-thawing treatments and covalent crosslinks were built via the boronic ester bonding. As-prepared hydrogel possessed significantly improved mechanical performance because the boronic ester bonding, on the one hand, well associated the two kinds of polymer chains, and on the other hand, played the role of 'sacrificial crosslinks'. Furthermore, the occurrence of dynamic boronic ester bonding gave the hydrogel strain- and temperature-sensitive ionic conductivity, and therefore, the hydrogels could be used to identify human motions and as-resulted environmental temperature alterations, and worked well in various scenarios. This work activates new application of CMK in the multimodal sensing field, and also proposes an intriguing way of building multiple crosslinks in the KGM derivative-based hydrogels.

Gold nanorod@void@polypyrrole yolk@shell nanostructures: Synchronous regulation of photothermal and drug delivery performance for synergistic cancer therapy.

Synergistic therapy has been emerging as new trend for effective tumor treatment due to synchronous function and cooperative reinforcement of multi therapeutic modalities. Herein, gold nanorods (GNRs) encapsulated into polypyrrole (PPy) shell with tunable void space (GNRs@Void@PPy) showing yolk@shell nanostructures were innovatively designed. The exploitation of dual near-infrared (NIR) absorptive species offered synergistic enhancement of photothermal performance. In addition, the manipulation of the void space between them provided additional benefits of high drug encapsulation efficiency (92.6%) and, interestingly, tumor microenvironment and NIR irradiation triggered targeted drug releasing. Moreover, the GNRs@Void@PPy exhibited excellent biocompatibility, and optimal curative effect by chemo-photothermal synergistic therapy was achieved through both in vitro and in vivo antitumor activity investigation.

Artesunate-loaded poly (lactic-co-glycolic acid)/polydopamine-manganese oxides nanoparticles as an oxidase mimic for tumor chemo-catalytic therapy.

Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application as a first-line agent in clinic. To improve the cure efficacy of cancer, nanozyme with enzyme-like activity has now been extensively investigated as a new strategy for tumor treatment. Herein, an anti-tumor platform based on manganese oxides (MnOx) modified poly (lactic-co-glycolic acid) (PLGA)@polydopamine (PDA) nanoparticles (PP-MnOx NPs) as an oxidase mimic was developed. PP-MnOx NPs could not only produce abundant reactive oxygen species to inhibit tumor growth taking advantage of their oxidase-like activity, but also encapsulate and release antitumor drug (artesunate) to function as chemotherapy, achieving remarkable synergistic chemo-catalytic therapeutic effects. As an oxidase mimics, PP-MnOx NPs induced the decrease of mitochondrial membrane potential, down-regulation of Bcl-2, as well as activation of Bax and Caspase-3, demonstrating that the apoptosis triggered by PP-MnOx NPs was mediated via mitochondrial pathways. Importantly, the artesunate in PP-MnOx NPs further promoted this apoptosis. In addition, Mn ions released from PP-MnOx NPs facilitated the tumor-microenvironment-specific T1-weighted magnetic resonance imaging. Taken together, this study well clarifies the antitumor mechanism of artesunate-loaded PP-MnOx NPs and offer a synergistic chemo-catalytic strategy for tumor theranostics.

Controllable Synthesis of Gold Nanorod/Conducting Polymer Core/Shell Hybrids Toward in Vitro and in Vivo near-Infrared Photothermal Therapy.

Photothermal therapy (PTT) is a minimally invasive tumor treatment technology, and is regarded as a potential anticancer strategy because of its targeted destruction and low toxicity. Specifically, near-infrared light-induced PTT has attracted intriguing interest because of the high transparency of tissue, blood, and water. However, effective PTT generally requires the assistance of photothermal agents. Gold nanorods (GNRs) and conducting polymer are often used as photothermal materials because of their high absorption efficiency and photothermal conversion efficiency. Herein, we combined GNRs with poly( o-methoxyaniline) (POMA, a polyaniline derivative) to form GNRs/POMA core/shell hybrids through the surfactant-assisted chemical oxidative polymerization route and studied their photothermal conversion properties. The configuration of GNRs/POMA core/shell hybrids has been precisely controlled through adjusting the monomer concentration, and the relationship between morphology and absorption band of GNRs/POMA core/shell hybrids has been revealed. Finally, the in vitro and in vivo experiments were performed, and the results indicated that the GNRs/POMA core/shell hybrids with optimized absorbance at around 808 nm exhibited the best performance on photothermal therapy under 808 nm NIR laser irradiation.

Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections.

The use of natural substance to ward off microbial infections has a long history. However, the large-scale production of natural extracts often reduces antibacterial potency, thus limiting practical applications. Here we present a strategy for converting natural organosulfur compounds into nano-iron sulfides that exhibit enhanced antibacterial activity. We show that compared to garlic-derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold increase in antibacterial efficacy to kill several pathogenic and drug-resistant bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released from nano-iron sulfides possess potent bactericidal activity and the release of polysulfanes can be accelerated by the enzyme-like activity of nano-iron sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides can effectively disrupt pathogenic biofilms on human teeth and accelerate infected-wound healing. Together, our approach to convert organosulfur compounds into inorganic polysulfides potentially provides an antibacterial alternative to combat bacterial infections.

Interactions between flavonoids and hemoglobin in lecithin liposomes.

In this paper, the binding of flavonoids (quercetin and rutin) to hemoglobin (Hb) have been investigated by fluorescence, absorption spectroscopy and circular dichroism (CD) spectroscopy. The binding parameters and binding mode between flavonoids and Hb are determined and the results of CD and synchronous fluorescence spectra indicate a conformational change of Hb with addition of flavonoids. The effects of lecithin liposomes on the binding parameter of quercetin and rutin to Hb are also studied. When incorporated into liposome, flavonoids can reduce the fluorescence of tryptophanyl residues of Hb to a lesser extent. The difference of the structure characteristics between quercetin and rutin has a significant effect on their binding affinity for Hb.

Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy.

Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn2+-coordinated doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn2+-PDA@DOX/PLGA nanoparticles. In our system, Mn2+-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn2+-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.

Drug-loaded chondroitin sulfate-based nanogels: preparation and characterization.

Chondroitin sulfate-based (NMChS) nanogels synthesized by inverse microemulsion polymerization method for drug delivery were reported. The properties of NMChS were investigated by light scattering, FTIR, (1)H NMR and transmission electron microscopy observations. The results showed that the size of NMChS nanogels could be controlled in the range of 145-340 nm by changing the degree of maleoyl substitution of chondroitin sulfate, and these nanogels were responsive to pH changes, which exhibited extended stability in aqueous media and low cytotoxicity in vitro by MTT assays. When these nanogels were loaded with doxorubicin hydrochloride (DOX·HCl), a cytotoxic drug for cancer treatment, the high loading ability and the pH triggered-release of drug were obtained due to the electrostatic interactions between drug and matrix, and the pore size of the polymer network. This study clearly showed that the chondroitin sulfate-based nanogels are biocompatible and biodegradable, rendering potential for drug delivery applications.

Chondroitin sulfate functionalized mesostructured silica nanoparticles as biocompatible carriers for drug delivery.

Mesoporous silica nanoparticles (MSNs) have garnered a great deal of attention as potential carriers for therapeutic payloads. Here, we report a pH-responsive drug-carrier based on chondroitin sulfate functionalized mesostructured silica nanoparticles (NMChS-MSNs) ie, the amidation between NMChS macromer and amino group functionalized MSNs. The prepared nanoparticles were characterized using dynamic light scattering, fourier transform infrared spectroscopy and transmission electron microscopy. The resultant NMChS-MSNs were uniform spherical nanoparticles with a mean diameter of approximately 74 nm. Due to the covalent graft of hydrophilic and pH responsive NMChS, the NMChS-MSNs could be well dispersed in aqueous solution, which is favorable to being utilized as drug carriers to construct a pH-responsive controlled drug delivery system. Doxorubicin hydrochloride (DOX), a well-known anticancer drug, could be effectively loaded into the channels of NMChS-MSNs through electrostatic interactions between drug and matrix. The drug release rate of DOX@NMChS-MSNs was pH dependent and increased with the decrease of pH. The in vitro cytotoxicity test indicated that NMChS-MSNs were highly biocompatible and suitable to use as drug carriers. Our results imply that chondroitin sulfate functionalized nanoparticles are promising platforms to construct the pH-responsive controlled drug delivery systems for cancer therapy.