2. Academic Validation
  3. A biomimetic multimodal nanoplatform combining neutrophil-coated two-dimensional metalloporphyrinic framework nanosheet and exendin-4 to treat obesity-related osteoporosis

A biomimetic multimodal nanoplatform combining neutrophil-coated two-dimensional metalloporphyrinic framework nanosheet and exendin-4 to treat obesity-related osteoporosis

  • Mater Today Bio. 2025 Jun 21:33:102009. doi: 10.1016/j.mtbio.2025.102009.
Qifan Yang 1,  Jing Liu 2,  Yanwei Liu 1,  Shun Liu 1,  Xiaokang Wei 1,  Yilin Yang 1,  Weijie Zhang 1,  Shuqi Zhang 1,  Maosheng Zhang 1,  Bin Liu 3,  Xinyu Wang 4,  Dong Zhu 1
Affiliations

Affiliations

  • 1 Department of Orthopedic Traumatology, The First Hospital of Jilin University, Changchun, 130000, Jilin Province, PR China.
  • 2 Gynecology and obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, 250000, PR China.
  • 3 Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, 130000, Jilin Province, PR China.
  • 4 Department of Pediatric Respiratory Medicine, Children's Medical Center, The First Hospital of Jilin University, Changchun, 130000, Jilin Province, PR China.
PMID: 40673132 DOI: 10.1016/j.mtbio.2025.102009
Abstract

Background: Obesity-induced osteoporosis is a prevalent complication among obese individuals. Conventional anti-osteoporosis medications often lack therapeutic specificity and may exacerbate lipid metabolism disorders. Consequently, identifying suitable pharmacological interventions for obesity-induced osteoporosis, elucidating its underlying biological mechanisms, and developing nanodrug delivery systems with enhanced biocompatibility and targeted delivery remain significant challenges.

Methods: This study reveals that the pathogenesis of obesity-induced osteoporosis is primarily driven by excessive Mitophagy. Notably, Exendin-4 (Ex-4) has been shown to ameliorate Mitophagy and mitigate obesity-induced osteoporosis. The nanocomposite DSPE-PEG-ALN (DPA)@Neutrophil membrane (NM)@Cu-TCPP(Zn)/Ex-4 (CTZE), characterized by high biocompatibility and Reactive Oxygen Species (ROS) responsiveness, effectively targets bone tissue, reduces ROS levels, and regulates the release of Cu2+, Zn2+, Ex-4, and Alendronate (ALN). This composite interferes with B-cell lymphoma-2 (BCL2)- Beclin-1 (BECN1) binding via the tet methylcytosine dioxygenase 2 (TET2)/PTEN-induced putative kinase protein 1 (PINK1)/Parkin (E3 ubiquitin-protein Ligase parkin) pathway, thereby promoting osteoblast differentiation and mineralization. The safety and efficacy of this nano-delivery platform were validated in a mouse model of obesity-induced osteoporosis.

Conclusions: In summary, our study illustrates that excessive Mitophagy plays a crucial role in obesity-induced osteoporosis. Furthermore, DPA@NM@CTZE exhibits significant potential for the precise treatment of obesity-induced osteoporosis, mitigating the side effects of Ex-4, and enhancing the bone microenvironment.

Keywords

Alendronate; Cu-TCPP(Zn); Exendin- 4; Mitophagy; Obesity-induced osteoporosis.

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