Publications by authors named "Chang-Ming Dong"

Despite the great progress of various multifunctional wound dressings, it is challenging to simultaneously achieve complete healing and functional remodeling for diabetic foot ulcers and refractory chronic wounds. Aiming to comprehensively regulate chronic inflammation, angiogenesis, and metabolism processes, herein, a novel kind of dynamic hyaluronic acid (HA) hydrogel was designed by combining boronate and coordination chemistry. Besides having injectability, self-healing, and detachment properties, dynamic HA hydrogels presented diabetic wound-responsive degradation and controllable HS release.

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Chronic diabetic wounds seriously threaten the health and life of human beings, however, it is challenging to develop pluripotent dressings that comprehensively remodel inflammation microenvironment, neovascularization and reepithelization to achieve high performance healing in diabetic wounds. Herein we construct a bioinspired polysaccharide coordinated hydrogel composed of bisphosphate-modified β-glucan (BG) with bioactive metal ions of Zn and Mg, in which multiple chelation enables fast gelation, self-healing, and dynamically sealing wounds. In vitro Mg release from BGM or BGMZ could promote intracellular uptake of Zn through upregulating Zn-related transporter protein ZIP6 while intracellular Mg remained relatively stable via downregulating the Mg transporter protein of MagT1.

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It is challenging for nanovaccines (NVs) to effectively deliver antigens/neoantigens to prime specifically potent immunities and remodel immunosuppressive tumor microenvironment (TME) for combating immune "cold" cancers. Herein, a novel kind of mannosylated fluoropolypeptide NVs of MFPCOFG (i.e.

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Fatal massive hemorrhage and diabetic wound healing are world widely challenging in surgical managements, and uncontrolled bleeding, chronic inflammation and damaged remodeling heavily hinder the whole healing processes. Considering hemostasis, inflammation and wound microenvironment cooperatively affect the healing progression, we design all-in-one beta-glucan (BG) hybrid hydrogels reinforced with laponite nanoclay that demonstrate tunable tissue adhesion, resistant vascular burst pressure and cooperative wound microenvironment regulation for arterial hemostasis and diabetic wound prohealing. Those hydrogels had honeycomb-like porous microstructure with average pore size of 7-19 μm, tissue adhesion strength of 18-46 kPa, and vascular burst pressure of 58-174 mmHg to achieve superior hemostasis in rat liver and femoral artery models.

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Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 μm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation.

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Regulating the wound microenvironment to promote proliferation, vascularization, and wound healing is challenging for hemostats and wound dressings. Herein, polypeptide composite hydrogels have been simply fabricated by mixing a smaller amount of metal ion-coordinated nanoparticles into dopamine-modified poly(L-glutamic acid) (PGA), which had a microporous size of 10-16 μm, photothermal conversion ability, good biocompatibility, and multiple biological activities. scratch healing of fibroblast L929 cells and the tube formation of HUVECs provide evidence that the PGA composite hydrogels could promote cell proliferation, migration, and angiogenesis with the assistance of mild photothermia.

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Ferroptosis is a novel type of iron-dependent non-apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug-resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H S), and immunotherapy (IT). To be noted, the combo therapies such as FT-CT, FT-PTT, FT-GT, and FT-IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects.

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Owing to having a unique mechanism to kill cancer cells via the membrane accumulation of lipid peroxide (LPO) and the downregulation of glutathione peroxidase-4 (GPX-4), the ferroptosis therapy (FT) of tumors based on the Fenton reaction of iron nanoparticles has been receiving much attention in the past decade; however, there are some hurdles including the uncontrollable release of iron ions, slower kinetics of the intracellular Fenton reaction, and poor efficacy of FT that need to be overcome. Considering cooperative coordination of a multivalent thiol-pendant polypeptide ligand with iron ions, we put forward a facile strategy for constructing the iron-coordinated nanohybrid of methacryloyloxyethyl phosphorylcholine-grafted polycysteine/iron ions/tannic acid (i.e.

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Tumor microenvironment responsive nanomedicine has drawn considerable attention for combination therapy, but still remains a significant challenge for less side effects and enhanced anti-tumor efficiency. Herein, we develop a pH/ROS dual-responsive supramolecular polypeptide nanoprodrug (PFW-DOX/GOD) by using pillar[5]arene-based host-guest strategy for combined glucose degradation, chemodynamic therapy (CDT), and chemotherapy (CT). The PFW-DOX/GOD consists of a pH-responsive ferrocene/pillar[5]arene-containing polypeptide, a ROS-responsive polyprodrug, and encapsulated glucose oxidase (GOD).

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Supramolecular nanomedicine assembly combined with polypeptide prodrug could become a powerful strategy to minimize drug leakage in blood circulation and trigger sufficient drug release at tumor tissue. Here, we developed a charge-reversal amphiphilic pillar[5]arene-modified polypeptide (P5-PLL-DMA), and reactive oxygen species (ROS)-sensitive polypeptide prodrug (P-PLL-DOX) including a ROS-cleavable thioketal (TK) linker between doxorubicin (DOX) and poly(-lysine) (PLL), which could assemble via pillar[5]arene host-guest recognition, and further encapsulate chlorin e6 (Ce6) to obtain a supramolecular polypeptide prodrug (SPP-DOX/Ce6). The chemical conjugation to load drugs of DOX and the negatively charge of SPP-DOX/Ce6 could prevent premature drug leakage, and reduce undesirable interaction with serum proteins to enhance stability under physiological conditions (pH 7.

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Stimuli-responsive prodrug-based nanoplatform with synergistic antitumor activity is of central importance to the development of promising nanomedicines for cancer therapy. Here, we describe a polydopamine-drug conjugate nanocomposite (ZP-PDA-DOX) with targeted cancer photothermal-chemotherapy (PTT-CT), which constructed by a gradual copolymerization of dopamine (DA) and pH-sensitive dopamine-derived prodrug (DA-DOX) into the porous channels of zeolite imidazolate frameworks-8 (ZIF-8), followed by PEGylation with amino-terminated folic acid-polyethylene glycol (NH -PEG-FA) to acquire the high biocompatibility, specificity, and excellent tumor-targeting property. The incorporation of polydopamine strengthened the stability and dispersion of ZIF-8, and also conferred photothermal conversion effect.

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Polymeric hydrogels have been increasingly studied for wound sealants, adhesives, hemostats, and dressings, however, multi-component gelation, adhesion-causing tissue damage, inefficient hemostasis, and skin scarring in wound healing hamper their advances. So it is urgent to develop multifunctional single-component polymeric hydrogels with benign tissue detachment, high performance hemostasis, and scarless wound healing attributes. Herein, a dopamine-modified poly(l-glutamate) hydrogel at an ultralow concentration of 0.

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Ferroptosis therapy (FT) based on the Fenton reaction of ferrous nanoparticles has been becoming a unique strategy for cancer treatment; however, current ferrous nanoparticles suffer from slower Fenton reaction kinetics, lower ferroptosis efficacy, and long-term toxicity, so it is urgent to construct biocompatible ferrous nanomaterials with highly efficient Fenton reaction activity for cancer FT. Inspired by single-atom catalysis and size-determined tumor penetration, we conceived an innovative strategy for constructing ultrasmall zwitterionic polypeptide-coordinated nanohybrids of PCGA@FeNP with about 6 nm by utilizing thiol/hydroxyl-iron cooperative coordination chemistry. The ultrasmall size, unsaturated ferrous coordination, and intracellular acidic pH could accelerate the Fenton reaction, thus boosting the efficacy of ferroptosis.

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Stimuli-responsive polypeptide nanoassemblies exhibit great potentials for cancer nanomedicines because of desirable biocompatibility and biodegradability, unique secondary conformations, varying functionalities, and especially the stimuli-enhanced therapeutic efficacy and reduced side effect. This review introduces the design and fabrication of stimuli-responsive polypeptide nanoassemblies that exhibit endogenous stimuli (e.g.

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The second near infrared photoacoustic imaging (NIR-II PAI) and photothermal therapy (NIR-II PTT) have attracted wide interest in cancer theranostics because of maximum permission exposure (MPE), deep penetration, and lower scattering and background noise compared to NIR-I counterparts; however, it is imperative to develop biocompatible nanomaterials having NIR-II response. By utilizing multivalent Au-S coordination bonds, we constructed a zwitterionic polypeptide nanocomposite of PMC@AuNP with a suitable size of 48 ± 2 nm, which possessed a strong and broad absorbance at 650-1100 nm and an excellent photothermal conversion efficiency of 49.5%.

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Multidrug resistance (MDR) induced by the overexpression of P-glycoprotein (P-gp) transporters mainly leads to chemotherapy (CT) failure. Herein, a NIR/pH dual-sensitive charge-reversal polypeptide nanocomposite (PDA-PLC) was developed for co-delivering a nitric oxide (NO) donor and doxorubicin (DOX). Under near-infrared (NIR) irradiation, the released high-concentration of NO gas inhibited the P-gp expression to sensitize the chemotherapeutic medicine DOX and assisted photothermal therapy (PTT) to eradicate cancer cells without skin scarring.

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Over the past decades, near infrared light (NIR)-sensitive photothermal agents (PTAs) that can efficiently absorb light and generate heat have been investigated worldwide for cancer photothermal therapy (PTT) and the combination treatments, which have some peculiar advantages including spatiotemporal targeting, the ability-to-reverse multidrug resistance, the immunity-stimulating function, and the synergistic effect in combination treatments. In this review, we first focus on emerging melanin-like polymers and coordination polyphenol polymer-based PTAs that hold transition potential because of their facile synthesis and good biocompatibility/biodegradability. We briefly introduce polymeric PTAs for emerging NIR-II (1000-1700 nm) PTT in deep tumors to overcome shallow penetration depth and threshold irradiation intensity of NIR-I (700-900 nm).

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Efficient therapeuic proteins' delivery into mammalian cells and subcellular transport (e.g., fast escape from endolysosomes into cytoplasm) are two key biological barriers that need to be overcome for antigen-based immunotherapy and related biomedical applications.

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Combating multidrug resistance (MDR) of tumors is still challenging for clinical chemotherapy, cocktail chemotherapy (CCT), and currently widely-studied nanodrug-based treatments. Inspired by different MDR-overcoming and antitumor mechanisms of CCT and photothermal therapy (PT), a dual drug-paired polyprodrug nanoparticle (PDCN25-CDDP) was constructed to achieve the combination therapy PT-CCT for reversing MDR and combating multidrug resistant cancers. The PT-CCT treatment can greatly downregulate the P-gp expression level and achieve utmost MDR-reversal and antitumor efficacy by both a cocktail effect of CCT and a synergistic effect of CCT with PT; meanwhile, PT can inhibit the expression of heat shock protein 90 and enhance the thermosensitivity of cancer cells.

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Multidrug resistance (MDR) of cancers that results from overexpression of a P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypeptide nanomedicines. Herein, a novel polypeptide nanocomposite PNOC-PDA that integrates heat-sensitive NO gas delivery and photothermal conversion attributes can overcome MDR and maximize CT; meanwhile the optimized CT and intracellular high-concentration NO gas can assist a mild photothermal therapy (PTT) to eradicate cancer cells. The triple therapies produced a superior and synergistic effect on MDR-reversal and killing MCF-7/ADR in vitro, and the P-gp expression level was downregulated to 46%, as confirmed by means of MTT, Western blot, flow cytometry, and confocal laser scanning microscopy.

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Although photothermal therapy (PT) and photothermal-chemotherapy (PT-CT) treatments have been used to achieve complete ablation of solid tumors, they are often implemented at more than 50 °C under high intensity and using a high dose of NIR irradiation, concomitantly inducing heavy skin burning, tissue damage, and ugly scarring. Moreover, the residual tumor cells at the treated site cannot be completely eradicated, resulting in tumor recurrence and metathesis. These key obstacles have prohibited PT and PT-CT treatments from transitioning to clinical use, therefore achieving traceless ablation of solid tumors without recurrence is still a challenge for real applications.

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Some of the biomedical polymer-drug conjugates are being translated into clinical trials; however, they intrinsically lack photothermal and multi-imaging capabilities, hindering them from imaging-guided precision cancer therapy and complete tumor regression. We introduce a new concept of all-in-one biopolymer-drug conjugate nanotheranostics and prepare a kind of intracellular pH-sensitive polydopamine-doxorubicin (DOX) conjugate nanoparticles (PDCNs) under mild conditions. Significantly, this strategy integrates polymeric prodrug-induced chemotherapy (CT), near-infrared (NIR) light-mediated photothermal therapy (PT), and triple modalities including DOX self-fluorescence, photothermal, and photoacoustic (PA) imaging into one conjugate nanoparticle.

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Increasing efforts are being made on controlled photopolymerization methodologies; however, the previous polymerization systems need additional photoactive initiators or catalysts. The controlled synthesis of the hyperbranched polypeptide is still challenging, and developing a photopolymerization method to prepare a hyperbranched polypeptide is urgent for constructing biodegradable polymers and biomaterials. Without addition of any initiator/catalyst, we combine the inimer (initiator + monomer) ring-opening polymerization (ROP) and photocaged chemistry to prepare hyperbranched and linear polypeptides.

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To integrate cocktail chemotherapy with photothermal therapy into one biocompatible and biodegradable nanocarrier, the plasmonic, lactose-targeted, and dual anticancer drugs-loaded polypeptide composite nanoparticles were for the first time fabricated under mild conditions. The glyco-PEGylated polypeptide micelles that self-assembled from the lactose (LAC) and PEG grafted polycysteine terpolymer were used as templates to generate the plasmonic composite nanoparticles, as mainly characterized by DLS, TEM, SEM, and XPS. These composite nanoparticles showed a broad and strong near-infrared (NIR) absorption at 650-1100 nm and increased the temperature of phosphate buffer solution by 30.

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Biodegradable, biocompatible polypeptide micelles were used as a reducing agent and template in an autoreduction method for preparing plasmonic gold-embedded polypeptide micelles under mild conditions. The micelles were fully characterized by DLS, TEM, SEM, and AFM. The in situ reduced gold was embedded in the interior core of the disulfide bond-cross-linked polypeptide micelles by forming multivalent Au-S bonds.

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