Thymopentin-integrated self-assembling nanoplatform for enhanced photo-immunotherapy in diabetic wound healing

Diabetic wounds represent a significant clinical challenge owing to infection, oxidative stress, and immune dysregulation. In this study, a multifunctional photoimmunotherapy nanoplatform (I-P-T NPs) was developed through the self-assembly of the near-infrared photosensitizer IR820, the immunomodulatory agent thymopentin (TP5), and the antioxidant phloretin (Phl) via intermolecular hydrogen bonding and hydrophobic interactions. This nanoplatform integrates photothermal therapy (PTT), immune modulation, and reactive oxygen species scavenging to address the infection-oxidation-immunosuppression triad in diabetic wounds. The I-P-T NPs exhibited robust photothermal conversion under 808 nm irradiation, generating localized hyperthermia with antibacterial effects. In vitro experiments demonstrated that I-P-T NPs promoted M2 macrophage polarization, reduced oxidative stress, enhanced endothelial and keratinocyte migration, and suppressed pro-inflammatory cytokine release. Additionally, the nanoplatform displayed potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In a streptozotocin-induced diabetic mouse model with infected wounds, topical application of I-P-T NPs combined with photothermal treatment accelerated wound closure, enhanced re-epithelialization and collagen deposition, and mitigated inflammation. The self-assembled design improved the solubility of Phl and enabled spatiotemporally controlled delivery of multiple therapeutic components. No significant systemic toxicity was observed, confirming the biocompatibility of I-P-T NPs. This study presents a novel nanoplatform that synergistically combines photothermal sterilization, TP5-mediated immune regulation, and Phl-driven antioxidant effects, offering a promising strategy for managing complex diabetic wounds. This modular design highlights the potential for translating multifunctional nanotherapies into clinical applications for the treatment of chronic wounds.