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A pseudohomogeneous nanocarrier based on carbon quantum dots decorated with arginine as an efficient gene delivery vehicle.

ABSTRACT: A pseudohomogeneous carrier as an emerging term refers to subnanometric carbon-based vehicle with a high ability to interact with genetic materials to form stable carboplex and successfully transfer them into the cell which will result in inhibiting or expressing of therapeutic genes. Chitosan is a non-toxic polyaminosaccharide used as a precursor in the presence of citric acid to produce carbon quantum dots (CQDs), which decorated with arginine as a surface passivation agent with high amine density in hydrothermal methodology. The Arginine-CQDs are comprehensively characterized by Fourier-transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), Atomic force microscopy (AFM), field emission scanning electron microscope (FE-SEM), Energy-dispersive X-ray (EDX) mapping, fluorescence, High-resolution transmission electron microscopy (HR-TEM), zeta potential and X-ray powder diffraction (XRD). In this regard, for the first time, carboplex are formed by electrostatic conjugating of Arginine-CQDs with DNA to protect it from enzymatic degradation. Moreover, the carboplex, like the chitosan precursor, has not shown toxicity against AGS cell line. Interestingly, the Arginine-CQDs have exhibited an excellent ability to overcome cell barriers to deliver into cells compared to chitosan at the same weight ratio. The Arginine-CQDs/pEGFP (W/W) nanocomplex, not only lead to transfection with a relatively higher efficiency than PEI polymer, which is the "golden standard", but carboplex also demonstrates no significant toxicity. Indeed, the EGFP expression level has reached to 2.4 ± 0.2 via Arginine-CQDs carboplex at W/W 50 weight ratio. To the best of our knowledge, this is the first report includes chitosan-based CQDs functionalized by arginine which is applied to serve as a pseudohomogeneous vehicle for gene transfection.

SUBMITTER: Rezaei A

PROVIDER: S-EPMC8253742 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect. In the present study, we examined the utility of PEG5K-EB2 to deliver DOX to tumors. In addition, folic acid (FA) was coupled to the surface of the PEG5K-EB2 micelles (FA-PEG5K-EB2) to further improve the selective targetability of the system. DOX-loaded PEG5K-EB2 micelles were uniformly spherical particles with a diameter of approximately 20 nm. Incorporation of FA had minimal effect on the size of the particles. The DOX loading efficiency was as high as 91.7% and 93.5% for PEG5K-EB2 and FA-PEG5K-EB2, respectively. DOX formulated in PEG5K-EB2 micelles (with or without FA decoration) demonstrated sustained kinetics of DOX release compared to free DOX. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. P-gp ATPase assay showed that PEG5K-EB2 significantly inhibited the function of the P-gp efflux pump. The maximum tolerated dose of DOX-loaded PEG5K-EB2 micelles was 15 mg/kg in mice, which was 1.5-fold greater than that for free DOX. Pharmacokinetics (PK) and biodistribution studies showed that both types of DOX-loaded micelles, especially FA-PEG5K-EB2, were able to significantly prolong the blood circulation time of DOX and facilitate its preferential accumulation at the tumor tissue. Finally, DOX/PEG5K-EB2 mixed micelles demonstrated significantly enhanced tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil and the antitumor activity was further enhanced after the decoration by folic acid. Our data suggest that FA-PEG5K-EB2 micelles represent a promising DOX delivery system that warrants more study in the future.

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A pseudohomogeneous nanocarrier based on carbon quantum dots decorated with arginine as an efficient gene delivery vehicle.

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