Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Her...Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.展开更多
Natural remedies are gaining attention as promising approaches to alleviating inflammation,yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects.To ove...Natural remedies are gaining attention as promising approaches to alleviating inflammation,yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects.To overcome these limitations,we have developed a novel nano-antioxidant(EK)based on epigallocatechin gallate(EGCG)aimed at enhancing the oral and systemic bioavailability,as well as the anti-inflammatory efficacy,of curcumin(Cur)in conditions such as acute colon and kidney inflammation.EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine(K),resulting in the formation of EGCG oligomers.These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm.In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages,a key component in the body’s inflammatory response.By efficiently encapsulating curcumin within these EK nanoparticles,we create Cur@EK,a formulation that demonstrates a synergistic anti-inflammatory effect.Specifically,Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-αand IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages,highlighting its potent anti-inflammatory properties.When administered either orally or intravenously,Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury.These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact,offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.展开更多
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 accelerate...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/Mg^(2+)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(Mg^(2+))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 Mg^(2+)-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/Mg^(2+) hydrogel presents an excellent wound dressing with excellent tissue adhesion,wound healing,and antibacterial functions.展开更多
Biodegradable polymer particles have been used as dermal fillers for pre-clinical and clinical trials.The impact of material properties of polymers is very important to develop products for aesthetic medicine such as ...Biodegradable polymer particles have been used as dermal fillers for pre-clinical and clinical trials.The impact of material properties of polymers is very important to develop products for aesthetic medicine such as dermal fillers.Herein,eight biodegradable polymers with different molecular weights,chemical compositions or hydrophilic-hydrophobic properties were prepared and characterized for systematical study for aesthetic medicine applications.Polymer microspheres with 20-100 lmwere prepared.The in vitro degradation study showed that poly(L-lactic-co-glycolic acid)75/25 microspheres degraded the fastest,whereas poly(L-lactic acid)(PLLA)microspheres with intrinsic viscosity of 6.89([g]¼6.89)with the highest molecular weight showed the slowest degradation rate.After these microspheres were fabricated dermal fillers according to the formula of SculptraVR,they were injected subcutaneously into the back skin of rabbits.In vivo results demonstrated that the degradation rate of microspheres strongly correlated with the foreign body reaction and collagen regeneration was induced by microspheres.The microspheres with faster degradation rate induced inflammatory response and the collagen regeneration maintained in shorter time.PLLA([g]¼3.80)microsphere with a moderate molecular weight and degradation rate could strongly regenerate Type I and III collagen to maintain a long-term aesthetic medicine effect.These properties of size,morphology and degradation behavior would influence the foreign body reaction and collagen regeneration.展开更多
Inflammatory bowel disease(IBD)is a chronic and refractory condition characterized by disrupted epithelial barrier,dysregulated immune balance,and altered gut microbiota.Nano-enabled interventions for restoring gut ho...Inflammatory bowel disease(IBD)is a chronic and refractory condition characterized by disrupted epithelial barrier,dysregulated immune balance,and altered gut microbiota.Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD.Herein,we developed a combination of olsalazine(Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation.The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages.The composite of nanoneedles and inulin gel(Cu2(Olsa)/Gel)displayed a macroporous structure,improved bio-adhesion,and enhanced colon retention after oral administration.Mechanistically,the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies,resulting in significant alleviation of colitis in three animal models of IBD.Furthermore,analysis of gut microbiota revealed that Cu2(Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria.Overall,this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy,offering an efficient approach to restore intestinal homeostasis.展开更多
基金supported by the National Natural Science Foundation of China[52073216 and 51773130].
文摘Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.
基金financial support by the Med-X Innovation Programme of Med-X Center for Materials,Sichuan University(MCM202302)the Sichuan Science and Technology Program(2024NSFSC0605).
文摘Natural remedies are gaining attention as promising approaches to alleviating inflammation,yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects.To overcome these limitations,we have developed a novel nano-antioxidant(EK)based on epigallocatechin gallate(EGCG)aimed at enhancing the oral and systemic bioavailability,as well as the anti-inflammatory efficacy,of curcumin(Cur)in conditions such as acute colon and kidney inflammation.EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine(K),resulting in the formation of EGCG oligomers.These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm.In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages,a key component in the body’s inflammatory response.By efficiently encapsulating curcumin within these EK nanoparticles,we create Cur@EK,a formulation that demonstrates a synergistic anti-inflammatory effect.Specifically,Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-αand IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages,highlighting its potent anti-inflammatory properties.When administered either orally or intravenously,Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury.These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact,offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.
基金supported by the National Natural Science Foundation of China(No.51773130,52073216 and 51903172)National Science Foundation of Zhejiang province(LY20B040004).
文摘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/Mg^(2+)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(Mg^(2+))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 Mg^(2+)-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/Mg^(2+) hydrogel presents an excellent wound dressing with excellent tissue adhesion,wound healing,and antibacterial functions.
基金supported by the National Science Foundation of China(51773130)Sichuan Science and Technology Program(2019JDRC0098)+1 种基金SCU-Enterprise Joint Project(18H0350)Sichuan Province Health Department(18P J553).
文摘Biodegradable polymer particles have been used as dermal fillers for pre-clinical and clinical trials.The impact of material properties of polymers is very important to develop products for aesthetic medicine such as dermal fillers.Herein,eight biodegradable polymers with different molecular weights,chemical compositions or hydrophilic-hydrophobic properties were prepared and characterized for systematical study for aesthetic medicine applications.Polymer microspheres with 20-100 lmwere prepared.The in vitro degradation study showed that poly(L-lactic-co-glycolic acid)75/25 microspheres degraded the fastest,whereas poly(L-lactic acid)(PLLA)microspheres with intrinsic viscosity of 6.89([g]¼6.89)with the highest molecular weight showed the slowest degradation rate.After these microspheres were fabricated dermal fillers according to the formula of SculptraVR,they were injected subcutaneously into the back skin of rabbits.In vivo results demonstrated that the degradation rate of microspheres strongly correlated with the foreign body reaction and collagen regeneration was induced by microspheres.The microspheres with faster degradation rate induced inflammatory response and the collagen regeneration maintained in shorter time.PLLA([g]¼3.80)microsphere with a moderate molecular weight and degradation rate could strongly regenerate Type I and III collagen to maintain a long-term aesthetic medicine effect.These properties of size,morphology and degradation behavior would influence the foreign body reaction and collagen regeneration.
基金supported by the National Natural Science Foundation of China(51903172,52073216)the Sichuan Science and Technology Program(2022NSFSC1939).
文摘Inflammatory bowel disease(IBD)is a chronic and refractory condition characterized by disrupted epithelial barrier,dysregulated immune balance,and altered gut microbiota.Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD.Herein,we developed a combination of olsalazine(Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation.The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages.The composite of nanoneedles and inulin gel(Cu2(Olsa)/Gel)displayed a macroporous structure,improved bio-adhesion,and enhanced colon retention after oral administration.Mechanistically,the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies,resulting in significant alleviation of colitis in three animal models of IBD.Furthermore,analysis of gut microbiota revealed that Cu2(Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria.Overall,this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy,offering an efficient approach to restore intestinal homeostasis.
