Construction and Performance of CD44-targeted Teniposide Nano-delivery System for Anti-B-cell Lymphoma Activity in vitro
10.13865/j.cnki.cjbmb.2025.05.1008
- VernacularTitle:CD44靶向的替尼泊苷纳米递送系统的体外抗B细胞淋巴瘤作用
- Author:
Chuan-Min ZHANG
1
;
Si-Jing MEI
;
Lei HAN
;
Yuan-Wei SHI
;
Bo-Lian XIAO
;
Xiao-Li XIE
;
Quan-Ping SU
Author Information
1. 临沂市人民医院中心实验室,山东临沂 276000;临沂市肿瘤生物学重点实验室,山东临沂 276000;徐州医科大学肿瘤转化医学重点实验室培育建设点,江苏徐州 221004
- Publication Type:Journal Article
- Keywords:
teniposide;
CD44;
hyaluronic acid;
nano-delivery system(NDS);
B-cell lymphoma
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(6):815-825
- CountryChina
- Language:Chinese
-
Abstract:
Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.
