A salt-triggered multifunctional smart window derived from a dynamic polyampholyte hydrogel.

Hydrogel smart windows are promising candidates for the automatic modulation of light transmittance through thermo-, humidity-, and electrochromic mechanisms. However, thermo- and humidity-triggered hydrogel smart windows are usually passively controlled and are not convenient for achieving active actuation; electrochromic windows require complex assembly and energy input. In addition, existing hydrogel smart windows are susceptible to physical damage, which may significantly shorten their working life. Herein, a salt-triggered polyampholyte hydrogel (PAH) is developed as a novel smart window with active and facile actuation as well as self-healing ability. The dynamic ionic bonds in PAH can reversibly disassociate and reform in alternate aqueous sodium chloride solution (NaCl(aq.)) and H2O, accounting for the reversible transparency-shifting and efficient modulation of light transmittance. PAH also enables patterning through precisely localized treatment with NaCl(aq.), which is useful for one-time information input/storage. Information encryption can be further realized by embedding PAH into an inherently transparent hydrogel or pasting it on an information carrier; the visibility of information is in line with the transparency-shifting of PAH. Moreover, the dynamic ionic bonds can endow the PAH-derived hydrogel smart window with self-healing and automatic damage-repairing abilities without sacrificing light modulation. Thus, salt-triggered PAH provides a new idea for designing actively actuating hydrogel smart windows with multifunctionality.

A Nanounit Strategy Disrupts Energy Metabolism and Alleviates Immunosuppression for Cancer Therapy.

Aberrant energy metabolism not only endows tumor cells with unlimited proliferative capacity but also contributes to the establishment of the glucose-deficient/lactate-rich immunosuppressive tumor microenvironment (ITM) impairing antitumor immunity. Herein, a novel metabolic nanoregulator (D/B/CQ@ZIF-8@CS) was developed by enveloping 2-deoxy-d-glucose (2-DG), BAY-876, and chloroquine (CQ) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously deprive the energy/nutrition supply of tumor cells and relieve the ITM for synergetic tumor starvation-immunotherapy. Aerobic glycolysis, glucose uptake, and autophagy flux could be concurrently blocked by D/B/CQ@ZIF-8@CS, cutting off the nutrition/energy supply and the source of lactate. Furthermore, inhibition of glucose uptake and aerobic glycolysis could effectively reverse the glucose-deficient/lactate-rich ITM, thus functionally inactivating regulatory T cells and augmenting anti-CTLA-4 immunotherapy. Such a two-pronged strategy would provide new insights for the design of metabolic intervention-based synergistic cancer therapy.

Enhancing the Accumulation of Polymer Micelles by Selectively Dilating Tumor Blood Vessels with NO for Highly Effective Cancer Treatment.

The accumulation of nanoparticles in tumors by the enhanced permeability and retention (EPR) effect is effective and well known. However, how to maximize accumulation is still a bottleneck in the development of nanomedicine. Herein, a tumor vascular-targeted hybrid polymeric micelle, which has a great capacity to selectively augment the EPR effect of nanoparticles by dilating tumor blood vessels via the activity of nitric oxide (NO), is presented. Under neutral conditions, the micelle is stable, with a long blood circulation half-life due to the carboxylated poly(ethylene glycol) (PEG) layer; in mildly acidic tumor tissues, the micelle can selectively target the tumor blood vessels by the exposed cyclic Arg-Gly-Asp peptide (cRGD) peptides, which is realized with a pH-dependent hydrolysis of the monomethoxy PEG layer. Simultaneously, exposed copper ions catalyze the decomposition of endogenous NO donors, which generates NO in situ, leading to vasodilation and increased tumor vascular permeability. As a result, the accumulation of nanoparticles is significantly enhanced, and a high accumulation of doxorubicin in tumors is achieved at 48 h after injection. This high dose of therapeutic agent produces a large inhibition of tumor growth (94%) in cancer treatment, and shows no general toxicity, with 100% of the mice surviving the treatment regimen.

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy.

Mitochondrial-targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin-loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core-shell-SS-shell architecture are composed of a core of Fe3 O4 colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near-infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment.

Redox-responsive polyanhydride micelles for cancer therapy.

Biodegradable polyanhydrides possess unique features like those that they can predominantly undergo surface erosion, and the payloads can be released by a steady speed. However, there is little work that has been published to describe the polyanhydride micelles with redox-responsiveness as a nanocarrier for drug delivery. In this study, we develop one type of new amphiphilic polyanhydride copolymer containing disulfide bonds between the hydrophilic and hydrophobic segments. The copolymer can self-assemble into stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 69 nm. The disassembly behaviors of the micelles triggered by glutathione are evaluated from the changes of the micellar size, morphology and molecular weight. An approximate zero-order in vitro drug release mode with a fast speed can be achieved in a reducing and acid environment similar with that of tumor cells. In vitro cytotoxicity analysis demonstrate that the Cur-loaded micelles are of great efficiency in inhibiting the growth of cancer cells due to the rapidly intracellular delivery of therapeutic agent. Both the qualitative and quantitative results of the antitumor activity in 4T1 tumor-bearing BALB/c mice reveal that the redox-responsive micelles have a more significant therapeutic effect to artificial solid tumor compared to the redox-insensitive micelles. This study provides a new insight into the biomedical application of polyanhydrides in drug delivery.

Co-delivery of dexamethasone and green tea polyphenols using electrospun ultrafine fibers for effective treatment of keloid.

PURPOSE: The electrospun polymer ultrafine fiber meshes wereused to co-deliver dexamethasone (DEX) and green tea polyphenols (GTP) in order to acquire a suitable balance between effective treament of keloid and safety to the skin. METHODS: This co-delivery system was prepared with a simple electrospinning technology. Keloid model was established on the back of athymic nude mice with the human keloid tissues and the formulated fiber meshes were applied onto keloids for an in vivo evaluation on their therapeutic effects. RESULTS: Unlike other therapeutic formulations, these fiber meshes as a new surgical dressing possess multiple useful functions, including the capabilities of maintaining a moist environment, resisting bacterial infection and controlling the drug release. Hydrophobic DEX molecules inside the fiber meshes can be released successfully from the channels formed by the early release of the hydrophilic GTP molecules and then transported across the skin. A distinctive result acquired from histological analysis shows that after 3-month treatment, the DEX/GTP-loaded fiber meshes significantly induce the degradation of collagen fibers in keloid on the back of nude mice compared to the traditional treatment. CONCLUSION: The dressing formulation based on nanofibers provides a promising platform for the treatment of keloid.

Controlled green tea polyphenols release from electrospun PCL/MWCNTs composite nanofibers.

Poly(ɛ-caprolactone)/multi-walled carbon nanotubes (PCL/MWCNTs) composite nanofibers with various content of green tea polyphenols (GTP) were successfully fabricated via an electrospinning technology to maintain the chemical structural stability of GTP. The non-covalent interaction between MWCNTs and GTP was measured by UV-vis spectrophotometer and FT-IR. The topographical features of the nanofibers were characterized by scanning electron microscopy (SEM). The dispersibility of MWCNTs and the distribution of GTP in nanofibers were observed by transmission electron microscopy (TEM) and laser scanning confocal microscope (LSCM), respectively. In vitro degradation was also characterized in terms of the morphological change and the mass loss of the nanofiber meshes. In vitro GTP release behavior was investigated in phosphate-buffered solution (PBS) at 37°C. Alamar blue assays were performed to estimate the cytotoxicity of the nanofibers with normal osteoblast cells and the antiproliferative effects to A549 and Hep G2 tumor cells. The results exhibited that the GTP-loaded composite nanofibers possessed a significant inhibition effect to tumor cells. Therefore, GTP, as a multifunctional drug, encapsulated into polymer composite nanofibers, must have broad application prospects in cancer therapy.