Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy

• Published in: Bioactive materials Vol. 41; pp. 158 - 173
• Main Authors: Leng, Tongtong, Zhang, Long, Ma, Junping, Qu, Xiaoyan, Lei, Bo
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.11.2024; KeAi Publishing Communications Ltd; KeAi Communications Co., Ltd
• Subjects: Angiogenesis; Animal models; Anti-inflammatory; Anti-inflammatory agents; Antioxidants; Bioactive materials; Bioactive polymers; Bioavailability; Biocompatibility; Biodegradation; Biological activity; Cell adhesion & migration; Cell growth; Cell migration; Chromatography; Citrate polymer; Curcumin; Cytotoxicity; Drug resistance; Edema; Endothelial cells; Fourier transforms; Free radicals; In vivo methods and tests; Inflammation; Inflammatory diseases; Lung diseases; Lungs; Methicillin; Microscopy; Molecular modelling; Molecular weight; NF-κB protein; NMR; Nuclear magnetic resonance; Oxygen; Photoluminescence; Photons; Polyethylene glycol; Polyglycol; Polymerization; Polymers; Regenerative medicine; Robustness; Sequences; Side effects; Staphylococcus aureus; Staphylococcus infections; Tissue engineering; Transcriptomes; Wound healing; Wound infection; Bioactive materials; Bioactive polymers; Citrate polymer; Anti-inflammatory; Inflammatory diseases
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.07.002

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system. [Display omitted] •The amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nanooligomers were reported.•PCGC demonstrated the good cellular compatibility, hemocompatibility and enhanced cellular uptake.•PCGC could efficiently scavenge the reactive nitrogen and intracellular oxygen species.•PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF- κB.•PCGC could efficiently treat acute lung injury and infected wound injury.