ISSN : 2146-3123
E-ISSN : 2146-3131

Biomimetic Nanosystems for the Synergistic Delivery of miR-144/451a for Oral Squamous Cell Carcinoma
Kunshan Li1, Yongle Qiu1, Xin Liu1, Fang Huang2
1Department of Stomatology, Fourth Affiliated Hospital, Hebei Medical University, Hebei, China
2Department of Medical Oncology, Fourth Affiliated Hospital, Hebei Medical University, Hebei, China
DOI : 10.4274/balkanmedj.galenos.2022.2021-11-1

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 miR-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.

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