AniView Supports Diabetic Wound Healing Research: Highly Stable Aggregation-Induced Emission-Functionalized Histatin1 Coated With Platelet Vesicles for Diabetic Wound Healing

New progress has been made in platelet membrane nanoparticle–based therapy for diabetic wound healing.

Researchers Bin Yang from the Dermatology Hospital of Southern Medical University, in collaboration with Yuhui Liao from Kunming Medical University and Ningxia Medical University, have made new advances in the treatment of diabetic ulcers. Their findings were published in “Aggregate”  (IF = 13.9, Q1 top journal).

This study develops an Hst1-AIE@PNPs composite system that integrates long-term peptide stabilization, wound microenvironment regulation, and fluorescence-based visualization, providing a new strategy for enhancing diabetic wound healing and enabling dynamic monitoring of therapeutic delivery.

Diabetic ulcers impose a significant medical burden due to their multifactorial etiology, high disability rate, and high treatment costs. A major challenge lies in the vicious cycle between persistent inflammation and excessive oxidative stress: hyperglycemic microenvironments and microbial lipopolysaccharide (LPS) trigger oxidative damage, promote M1 macrophage polarization, and induce the secretion of inflammatory factors such as IL-1β and TNF-α, resulting in sustained neutrophil recruitment and prolonged inflammation. Meanwhile, the function of anti-inflammatory M2 macrophages is suppressed, leading to insufficient secretion of key repair factors such as IL-10 and TGF-β1 and hindering the transition of wounds into the proliferative phase. Existing bioactive-material-based therapies, such as recombinant growth factors and salivary histatin-1 (Hst1), can promote cell migration, angiogenesis, and collagen deposition, but peptides such as Hst1 are extremely unstable in the protease-rich wound environment. Previous studies have reported that Hst1 can undergo up to 92% degradation within 24 hours in chronic wound exudates, severely limiting its bioavailability and therapeutic efficacy.

To address these limitations, conventional delivery systems such as polyethylene glycol and hydrogels face challenges including poor biocompatibility and safety risks associated with exogenous materials. Platelet membrane-coated nanoparticles (PNPs) offer unique advantages: surface CD47 proteins can mediate immune evasion and prolong circulation time in vivo, while membrane receptors can efficiently adsorb LPS and inflammatory factors, directly improving the wound microenvironment. However, the lack of real-time monitoring of drug release limits the implementation of precision therapy. To overcome this challenge, the study developed an innovative solution based on aggregation-induced emission (AIE) materials, which exhibit significantly enhanced fluorescence in the aggregated state. By covalently conjugating AIE with Hst1 and encapsulating the conjugate within PNPs, the researchers constructed an Hst1-AIE@PNPs composite system integrating long-term stability, microenvironment regulation, and visualization.

The design provides three key advantages. First, PNPs serve as biomimetic carriers that effectively protect Hst1 from proteolytic degradation, with 76.1% retention after 24 hours in the wound environment compared with only 8% for free Hst1, representing a 9.5-fold improvement. Second, PNPs adsorb LPS and work synergistically with Hst1 to regulate macrophage phenotype transition by suppressing M1 polarization through the MAPK/NF-κB pathway, while simultaneously eliminating reactive oxygen species (ROS), thereby establishing dual anti-inflammatory and antioxidant mechanisms. Finally, AIE labeling enables fluorescence-enhanced visualization of drug accumulation at target sites, providing dynamic information for therapeutic evaluation. By integrating nanotechnology, molecular imaging, and immune regulation, this interdisciplinary strategy overcomes key microenvironmental barriers to diabetic wound healing and provides a new paradigm for advancing clinical translation.

Experiments using AniView

To evaluate the protective effect and sustained-release performance of PNPs on the antimicrobial peptide Hst1, fluorescence imaging of diabetic wounds treated with different drug formulations at different time points was performed using the AniView multimodal in vivo imaging system from Guangzhou Biolight Biotechnology (Figure 2). Compared with free AIE fluorescent molecules and the Hst1-AIE complex, the Hst1-AIE@PNPs treatment group showed significantly prolonged fluorescence retention. The free formulation exhibited more than 90% signal attenuation within 24 hours, whereas the PNPs group retained 76% of its initial signal at 24 hours and decreased to approximately 50% by 48 hours. Quantitative analysis (Figure 2C) further revealed its sustained-release kinetics: almost no drug release occurred during the first 12 hours, with more than 95% retention, followed by gradual release from 12 to 48 hours. This was in sharp contrast to the rapid enzymatic degradation of free Hst1-AIE. These results directly demonstrate that PNPs effectively protect Hst1 from proteolytic degradation in the wound environment, extending the duration of Hst1 bioactivity from less than 8 hours to more than 48 hours and providing a critical pharmacokinetic basis for subsequent wound-healing efficacy.

DOI: org/10.1002/agt2.70073