2. Academic Validation
  3. A Remote-Controlled Nanopump Delivers Oxygen to Boost Energy Production in Osteoarthritis

A Remote-Controlled Nanopump Delivers Oxygen to Boost Energy Production in Osteoarthritis

  • ACS Nano. 2025 Dec 23;19(50):42506-42525. doi: 10.1021/acsnano.5c15534.
Xiaowei Xia 1 2,  Wu Xu 1 2,  Zhiyuan He 1 2,  Yingjie Lu 1 2,  Yong Zhang 1 2,  Huilin Yang 1 2,  Lixin Huang 1 2,  Dinghua Jiang 1 2,  Lisong Li 1 2,  Yijian Zhang 1 2,  Xuesong Zhu 1 2 3
Affiliations

Affiliations

  • 1 Departmentof Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China.
  • 2 Orthopaedic Institute, Medical College, Soochow University, Suzhou 215000, China.
  • 3 Departmentof Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
PMID: 41363106 DOI: 10.1021/acsnano.5c15534
Abstract

The pro-energy synthesis strategy has been considered a promising approach for addressing degenerative disorders, including osteoarthritis (OA). However, the physiologically low oxygen tension in articular cartilage limits aerobic respiration and energy production. In this study, a Hemoglobin (Hb)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanopump was developed for efficient oxygen delivery. This nanopump was further functionalized with cartilage-targeting peptides (CZIF@Hb) and specifically guided to aggregate on chondrocytes. In response to active (ultrasonic driving) and passive stimuli (acidic microenvironment), CZIF@Hb underwent responsive disassembly. ZIF-8 drove CO2 adsorption, while Hb facilitated O2 release. These processes synergistically enhanced the tricarboxylic acid (TCA) cycle and subsequent Oxidative Phosphorylation (OXPHOS), thereby promoting adenosine triphosphate (ATP) generation. Mechanistically, in addition to direct oxygen supply, CZIF@Hb nanopump indirectly facilitated the incorporation of α-KG into the TCA cycle by activating the solute carrier family 1 member 5 (SLC1A5)/solute carrier family 38 member 2 (SLC38A2)-glutamate dehydrogenase 1 (GLUD1)-glutaminase (GLS) axis. The enhanced energy metabolism mitigated free radical-induced damage and concurrently promoted the formation of hyaline cartilage instead of fibrocartilage. Administration of CZIF@Hb nanopump exerted therapeutic effects on cartilage degeneration, subchondral bone sclerosis, and synovial inflammation. Overall, the oxygen-carrying nanoplatform offers a feasible strategy for overcoming energy deficits in hypometabolic organs.

Keywords

energy metabolism; fibrocartilage hyalinization; glutamine metabolism; oxygen delivery; ultrasound response.

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