Biomimetic Nanosystems for the Synergistic Delivery of miR-144/451a for Oral Squamous Cell Carcinoma

被引:10
作者
Li, Kunshan [1 ]
Qiu, Yongle [1 ]
Liu, Xin [1 ]
Huang, Fang [2 ]
机构
[1] Hebei Med Univ, Affiliated Hosp 4, Dept Stomatol, Shijiazhuang, Hebei, Peoples R China
[2] Hebei Med Univ, Affiliated Hosp 4, Dept Med Oncol, Shijiazhuang, Hebei, Peoples R China
关键词
MULTIPLE MIRNAS; GENE DELIVERY; STRATEGIES; EXPRESSION;
D O I
10.4274/balkanmedj.galenos.2022.2021-11-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The miR-144.451a cluster acts as a tumor suppressor in various tumors by synergistically inhibiting the proliferation, migration, and invasion of oral squamous cell carcinoma (OSCC). Aims: To achieve the synergistic delivery of the in iR-144/451a cluster for OSCC treatment by constructing chitosan nanoparticles (CAs) camouflaged with macrophage membranes. Study Design: A cell-culture study. Methods: CAs were prepared using the ionic cross-linking method, and biomimetic nanoparticles coloaded with the miR-144/451a cluster miR-144-source of macrophage-derived exosomes [MEXO]/CA-miR-451a) were prepared using the uptake-efflux method. The MEXO was detected by a bicinchoninic acid assay. The as-prepared biomimetic nanoparticles were then characterized to determine their protective effects on microRNAs (miRNAs). Moreover, the influence of the miR-144-MEXO/CA-miR-451a nanoparticles on the proliferation, migration, and invasion of OSCCs was evaluated. Finally, the effects of the biomimetic system on the expression of calcium-binding protein 39 (CAB39) and migration inhibitory factor (MIF) were detected using the real-time polymerase chain reaction and Western blot. Results: After coating the CAs with MEXO, their particle size increased from 113.1 +/- 3.4 nm to 143.2 +/- 14 nm, and their surface potential decreased from 26.34 +/- 0.4 mV to -10.3 +/- 1.6 mV. The expression of the MEXO marker protein was also observed on the biomimetic nanoparticles' surface. The system can protect miRNAs from RNase A degradation. Compared with the CAs cotransfected with free miR-144/451a cluster. CAs that are coloaded with miR-144-MEXO/CA-miR-451a nanoparticles substantially reduced the viability (p < 0.001), migration (p = 0.023), and invasion (p 0.004) of OSCC. These findings revealed the successful construction of biomimetic nanoparticles coloaded with the miR-144/451a cluster. CAB39 and MIF expression in OSCC treated with miR-144-MEXO/CA-miR-451a nanoparticles have significantly decreased compared with the miR-144/451a group (p < 0.05). Thus, the nanoparticles can effectively improve the inhibitory effects of the miR-144/451a cluster on OSCC. Conclusion: This study provided a new idea for the application of gene cotransfection to tumor treatment.
引用
收藏
页码:178 / 186
页数:9
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