Citation: Yeling Yuan, Lihua Du, Kejing Zeng, Yilu Zheng, Huaping Huang, Yu Shao, Wenqing Wang, Leping Yan, Jun Wu, Changhua Zhang, Hongman Xue, Haozhe He. Hyaluronic acid-modified MOF nanoparticles for encapsulating asparaginase in T-cell acute lymphoblastic leukemia treatment[J]. Chinese Chemical Letters, ;2026, 37(1): 111222. doi: 10.1016/j.cclet.2025.111222 shu

Hyaluronic acid-modified MOF nanoparticles for encapsulating asparaginase in T-cell acute lymphoblastic leukemia treatment

Yeling Yuan ^{a, 1} ,
Lihua Du ^{b, c, 1} ,
Kejing Zeng ^{d, 1} ,
Yilu Zheng ^{e, 1} ,
Huaping Huang ^{b, c} ,
Yu Shao ^b ,
Wenqing Wang ^{a, b} ,
Leping Yan ^{b, c, f} ,
Jun Wu ^{g, *,} ,
Changhua Zhang ^{b, c, *,} ,
Hongman Xue ^{a, *,} ,
Haozhe He ^{b, c, *,}

a.
Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
b.
Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
c.
Guangdong-Hong Kong-Macau University Joint Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
d.
Department of Endocrinology, Department of diabetes and obesity reversal research center, Guangdong Second Provincial General Hospital, Guangzhou 510317, China
e.
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
f.
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
g.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China

junwuhkust@ust.hk

zhchangh@mail.sysu.edu.cn

xuehongman@sysush.com

hehzh8@mail.sysu.edu.cn

Received Date: 17 February 2025
Revised Date: 12 April 2025
Accepted Date: 15 April 2025
Available Online: 17 April 2025

Figures(5)

T-cell acute lymphoblastic leukemia (T-ALL) is a common yet severe pediatric cancer treated with L-asparaginase (ASP). To boost the treatment's effectiveness and lessen its toxicity, enzyme@MOF nanoparticles were engineered with a hyaluronic acid (HA)-targeted polyethylene glycol (PEG) surface. These nanoparticles, termed ASP@MOF/PEG-HA, showed efficient uptake by drug-resistant T-ALL cells. The pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) based metal-organic framework (MOF) nanoparticles allowed the encapsulated ASP to significantly increase cytotoxicity against T-ALL cells. Furthermore, HA's ability to bind to T-ALL cells with elevated CD44 expression further induced apoptosis in CD44⁺ T-ALL cells with poor prognosis. In animal models, the nanoparticles improved survival rates and reduced the burden of leukemia, demonstrating substantial anti-leukemia effects. Thus, these nanoparticles offer an effective treatment approach for drug-resistant T-ALL cells characterized by increased CD44 expression.
- Carriers and controlled release materials,
- Drug delivery,
- L-Asparaginase,
- enzyme@MOF,
- T-ALL
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