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 ( < 0.001), migration ( = 0.023), and invasion ( = 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 ( < 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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| http://dx.doi.org/10.4274/balkanmedj.galenos.2022.2021-11-1 | DOI Listing |
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Biomimetic Nanosystems for the Synergistic Delivery of miR-144/451a for Oral Squamous Cell Carcinoma.
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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.
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