Bacterial infection is a vital factor to delay the wound healing process. The antibiotics abuse leads to drug resistance of some pathogenic bacteria. Non-antibiotic-dependent multifunctional ...biomaterials with accelerated wound healing performance are urgently desired. Herein, we reported a composite antibacterial hydrogel PDA-PAM/Mg2+ that shows excellent self-healing and tissue adhesive property, and photothermal antibacterial functions for accelerating wound healing. The gel was composed of polyacrylamide (PAM), polydopamine (PDA), and magnesium (Mg2+) and prepared via a two-step procedure: an alkali-induced dopamine pre-polymerization and followed radical polymerization process. The composite gel shows excellent tissue adhesiveness and Mg2+-synergized photothermal antibacterial activity, inducing a survival rate of 5.29% for S. aureus and 7.06% for E. coli after near infrared light irradiation. The composite hydrogel further demonstrated efficient bacteria inhibition, enhanced wound healing and collagen deposition in a full-thickness skin defect rat model. Together, the PDA-PAM/Mg2+ hydrogel presents an excellent wound dressing with excellent tissue adhesion, wound healing, and antibacterial functions.
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•A self-healing multifunctional hydrogel with photothermal antibacterial properties was developed and applied in wound healing.•The hydrogel exhibited enhanced self-healing and adhesion properties.•The hydrogel exhibited excellent photothermal effect and photothermal stability and repeatability.•The hydrogel could accelerate wound healing by promoting cell proliferation and collagen deposition.
Osteoarthritis (OA) is a common degenerative joint disease that can lead to disability. Blocking the complex malignant feedback loop system dominated by oxidative stress and pro-inflammatory factors ...is the key to treating OA. Here, we develop a multifunctional composite thermo-sensitive hydrogel (HPP@Cu gel), which is utilized by Poloxamer 407 (P407) and hyaluronic acid (HA) mixture as the gel matrix, then physically mixed with copper nanodots (Cu NDs) and platelet-rich plasma (PRP). Cu NDs is a novel nano-scavenger of reactive oxygen and nitrogen species (RONS) with efficient free radical scavenging activity. HPP@Cu gel is injected into the articular cavity, where it form an in situ gel that slowly released Cu NDs, HA, and PRP, prolonging the duration of drug action. Our results indicate that HPP@Cu gel could efficiently remove RONS from inflammatory sites and promote repolarization of macrophages to an anti-inflammatory phenotype. The HPP@Cu gel therapy dramatically reduces cartilage degradation and inflammatory factor production in OA rats. This study provides a reliable reference for the application of injectable hydrogels in inflammatory diseases associated with oxidative stress.
Porous polymer microspheres (PPMs) have been widely applied in various biomedical fields. Herein, the self‐assisted preparation of poly(ester‐thioether)‐based porous microspheres and hierarchical ...microcages, whose pore sizes can be controlled by varying the polymer structures, is reported. Poly(ester‐thioether)s with alkyl side chains (carbon atom numbers were 2, 4, and 8) can generate hollow porous microspheres; the longer alkyl chain length, the larger pore size of microspheres. The allyl‐modified poly(ester‐thioether) (PHBDT‐g‐C3) can form highly open, hierarchically interconnected microcages. A formation mechanism of these PPMs is proposed; the hydrophobic side chains‐mediated stabilization of oil droplets dictate the droplet aggregation and following solvent evaporation, which is the key to the formation of PPMs. The hierarchically interconnected microcages of PHBDT‐g‐C3 are due to the partially crosslinking of polymers. Pore sizes of PPMs can be further tuned by a simple mixing strategy of poly(ester‐thioether)s with different pore‐forming abilities. The potential application of these PPMs as H2O2‐responsive vehicles for delivery of hydrophobic (Nile Red) and hydrophilic (doxorubicin hydrochloride) cargos is also investigated. The microspheres with larger pore sizes show faster in vitro drug release. The poly(ester‐thioether)‐based polymer microspheres can open a new avenue for the design of PPMs and provide a H2O2‐responsive drug delivery platform.
A series of poly(ester‐thioether)‐based hollow porous microspheres and microcages are prepared by solvent evaporation method in the absence of porogens. The pore sizes of porous microspheres are reliant on the alkyl chain lengths and allyl chain in the polymer side chains. The longer alkyl chain leads to larger pore sizes and faster drug release.
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•Polymeric nanoparticles generated by PEG-Chrysin conjugates were fabricated.•π–π Stacking interaction within the DOX loaded nanoparticles was investigated.•The nanoparticles with ...short mPEG1000 chains exhibited higher anticancer activity.•The nanoparticle provides a new carrier for anticancer drug delivery.
Nanoparticle-based drug delivery systems promise the safety and efficacy of anticancer drugs. Herein, we presented a facile approach to fabricate novel nanoparticles generated by PEG-Chrysin conjugates for the delivery of anticancer drug doxorubicin. Chrysin was immobilized on the terminal group of methoxy poly(ethylene glycol) (mPEG) to form mPEG-Chrysin conjugate. The conjugates were self-assembled into nanoparticles. Doxorubicin (DOX) was loaded in the nanoparticles. The self-assembly, drug release profiles, interactions between nanoparticle and drug, cellular uptake and in vitro anticancer activity of the DOX loaded nanoparticles were investigated. The results showed that the mean diameters of drug loaded nanoparticles were below 200nm. Strong π–π stacking interaction was tested within the drug loaded nanoparticles. The drug release rate was closely related to the chain length of PEG, shorter PEG chain resulted faster release. The mPEG-Chrysin conjugate was non-toxic to both 3T3 fibroblasts and HepG2 cancer cells. The cellular uptake measurements demonstrated that the mPEG1000-Chrysin nanoparticles exhibited higher capability in endocytosis. The IC50 of drug loaded mPEG1000-Chrysin nanoparticles was 4.4μg/mL, which was much lower than that of drug loaded mPEG2000-Chrysin nanoparticles (6.8μg/mL). These nanoparticles provided a new strategy for fabricating antitumor drug delivery systems.
A facile method has been developed for the large‐scale synthesis of random copolypeptides composed of multiple (i.e., cationic, hydrophobic, and hydrophilic) amino acids and their relative ratios ...have been optimized for broad‐spectrum antibacterial effect. The copolypeptides obtained have measured compositions close to the design ratios in spite of the differing reactivities of the different amino acids. An optimized random copolypeptide of lysine, leucine, and serine (denoted as KLS‐3) mimicking the composition of LL‐37 host defense peptide gives broad spectrum antibacterial activity against clinically relevant Gram‐negative and Gram‐positive bacteria such as methicillin‐resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1) with minimum inhibitory concentrations (MICs) of 32–64 μg mL−1, as well as good MICs against multidrug resistant Gram‐negative bacteria of Escherichia coli EC 958 (64 μg mL−1) and Klebseilla pneumoniae PTR3 (128 μg mL−1). This method can be applied to the facile large‐scale copolymerization of multiple amino acids, including unnatural amino acids, to make effective antibacterial copolypeptides.
A facile method for the large‐scale synthesis of random polypeptides composed of multiple (i.e., cationic, hydrophobic, and hydrophilic) amino acids is proposed by using diphenylphosphoryl azide. The copolypeptides mimicking hose defense peptide LL‐37 and lipopeptide antibiotic polymyxin B show broad‐spectrum antibacterial effects against both Gram‐positive, Gram‐negative strains, and even multidrug‐resistant clinically relevant strains.
Metal–organic frameworks (MOFs) are a class of important porous, crystalline materials composed of metal ions (clusters) and organic ligands. Owing to the unique redox chemistry, photochemical and ...electrical property, and catalytic activity of Cu2+/+, copper-based MOFs (Cu-MOFs) have been recently and extensively explored in various biomedical fields. In this review, we first make a brief introduction to the synthesis of Cu-MOFs and their composites, and highlight the recent synthetic strategies of two most studied representatives, three-dimensional HKUST-1 and two-dimensional Cu-TCPP. The recent advances of Cu-MOFs in the applications of cancer treatment, bacterial inhibition, biosensing, biocatalysis, and wound healing are summarized and discussed. Furthermore, we propose a prospect of the future development of Cu-MOFs in biomedical fields and beyond.
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•Recent advances of copper-based metal–organic frameworks (Cu-MOFs) in biomedical fields are reviewed.•We introduced the synthesis of Cu-MOFs and their composites.•We highlight the progresses of Cu-MOFs in the fields of cancer and bacterial inhibition.•Biosensing of H2O2, glucose, nucleic acids, and bacteria by Cu-MOFs are presented.•Applications of Cu-MOFs in physiological catalysis and wound healing are provided.
Disulfiram (DSF) has been used as an alcoholism drug for 70 years. Recently, it has attracted increasing attention owing to the distinguished anticancer activity, which can be further potentiated by ...the supplementation of Cu2+. Although encouraging anticancer results are obtained in lab, the clinical outcomes of oral DSF are not satisfactory, which urges an in-depth understanding of the underlying mechanisms, bottlenecks, and proposal of potential methods to address the dilemma. In this review, a critical summarization of various molecular biological anticancer mechanisms of DSF/Cu2+ is provided and the predicament of orally delivering DSF in clinical oncotherapy is explained by the metabolic barriers. We highlight the recent advances in the DSF/Cu2+ delivery strategies and the emerging treatment regimens for cancer treatment. Last but not the least, we summarize the clinical trials regarding DSF and make a prospect of DSF/Cu-based cancer therapy.
The inflammatory bowel disease (IBD) is incurable, chronic, recrudescent disorders in the inflamed intestines. Current clinic treatments are challenged by systemic exposure-induced severe side ...effects, inefficiency after long-term treatment, and increased risks of infection and malignancy due to immunosuppression. Fortunately, naturally bioactive small molecules, reactive oxygen species scavengers (or antioxidants), and gut microbiota modulators have emerged as promising candidates for the IBD treatment. Polymeric systems have been engineered as a delivery vehicle to improve the bioavailability and efficacy of these therapeutic agents through targeting the mucosa and enhancing intestinal adhesion and retention, and reduce their systemic toxicity. Herein we survey polymer-derived drug delivery systems for combating the IBD. Advanced delivery technologies, therapeutic intervention strategies, and the principles for the construction of hierarchical, mucosa-targeting, and bioresponsive systems are elaborated, providing insights into design and development of from-bench-to-bedside drug delivery polymeric systems for the IBD treatment.
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•Polymer-derived drug delivery systems enable hierarchal functions in IBD treatment.•As drug carriers, various nano/micro and hybrid formulations are developed.•Harnessing polymer-biointerface interactions for efficient targeting/accumulation.•Polymeric delivery systems alleviate colitis by mono- and combination therapy.
Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC)2, is the ...crucial DSF’s metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu(II) and carboxylic groups in poly(ethylene glycol)-b-poly(ester-carbonate) (PEC) for efficient loading of Cu(DDC)2, which was generated by the in situ reaction of DSF and Cu(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu(II), and PEC. These Cu(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu(DDC)2-based chemotherapy and chemodynamic therapy mediated by bioavailable Cu(II) that was not in the form of Cu(DDC)2. The in vivo antitumor results demonstrated that the Cu(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.
Platinum-based chemotherapy is widely used to treat various cancers. However, exogenous platinum is likely to cause severe side effects and drug resistance induced by upregulated glutathione (GSH) in ...cancer cells poses a threat to the management of cancer progression and recurrence. Anticancer copper-organic complexes are excellent candidates to substitute platinum-based chemotherapeutics, exhibiting lower systemic toxicity and even overcoming platinum-based chemotherapy resistance. Here, we report the GSH-resistance of copper(II) bis(diethyldithiocarbamate) (CuET) and its reversal of cisplatin resistance in non-small-cell lung cancer
cuproptosis. Electrochemistry and UV-vis spectroscopy studies demonstrate that CuET possesses a lower reduction potential and the reaction inertness with GSH. Importantly, CuET overcomes the drug resistance of A549/DDP cells and the anticancer effect is hardly affected by intracellular GSH levels. To improve the solubility and bioavailability, bovine serum albumin-stabilized CuET nanoparticles (NPs) are prepared and they have a high drug loading content of 27.5% and excellent physiological stability.
studies manifest that CuET NPs augment the distributions in the cytosol and cytoskeleton, inducing cell death
cuproptosis in A549/DDP cells, which is distinctly different from the apoptosis pattern induced by cisplatin.
antitumor evaluation shows that the nanomedicine has superior biosafety and potent antitumor activity in a cisplatin-resistant tumor model. Our study suggests that copper-organic complex-based nanosystems could be a powerful toolbox to tackle the platinum-based drug resistance and systemic toxicity concerns.