Introduction: Recent advances in the field of poly (2-oxazolines) as bio-inspired synthetic pseudopeptides have proven their potential biomedical applications such as drug delivery and tissue engineering.
Methods: In order to fabricate a biodegradable micellar nanoparticle of poly (2-ethyl 2-oxazoline)-b-poly (benzyl L-glutamate) or pEOx-b-pBLG, "grafting-from" synthesis approach was used involving consecutive steps of cationic ring-opening polymerization of 2-ethyl-2-oxazoline, amine functionalization of pEOx using 1-Boc-piperazine and N-carboxyanhydride polymerization of γ-benzyl- L-glutamate. Following hydrolysis of the copolymer, the protecting γ-benzyl groups were removed yielding a double-hydrophilic block ionomer of pEOx-b-poly (L-glutamic acid). The polymers were characterized by FTIR, 1H-NMR, size exclusion chromatography and differential scanning calorimetry (DSC). Aqueous assembly of the polymers was investigated by pyrene assay, dynamic light scattering, and transmission electron microscopy. MTT cytotoxicity assay was also performed to determine the cytocompatibility in various tumor cell lines.
Results: The polymeric micelles presented a uni-modal size distribution with mean hydrodynamic diameter of 149.8 ± 10.6 nm and critical aggregation concentration of 60 µg/mL. The average molecular weight of pEOx increased from ~ 14 to 20 kDa for pEOx-b-poly (L-glutamic acid) as determined by light scattering (Debye plot), indicating a successful copolymerization. MTT assay showed little to no practical cytotoxicity at concentrations below 1 mg/mL.
Conclusion: Multi-step synthesis of pEOx-b-pBLG and subsequent alkaline hydrolysis were performed to obtain the block ionomer pEOx-b-poly (L-glutamic acid). Both pEOx-based copolymers can be considered for various potential applications such as loading and delivery of drugs, genes, and contrast agents either by chemical conjugation or physical loading.
Over‐expression of miR21 plays an important role in several cancers by promoting cancer cell proliferation, migration, invasion, and metastasis. Here, we attempted to prepare a beta cyclodextrin‐polyethyleneimine‐graphene quantum dot (βCD‐PEI‐GQD) nanocarrier for cellular delivery of miR21a. For this purpose, tosylated‐βCD and GQD were conjugated to branched PEI. The product was characterized by FTIR, 1H‐NMR, and fluorescence spectroscopy. The morphology, particle size distribution, and ζ‐potential of miR21a were examined by TEM and DLS following overnight incubation with βCD‐PEI‐GQD in aqueous media. The miR21 silencing was measured by stem‐loop RT‐PCR in HepG2 human hepatoma cell line. Cellular uptake and cell toxicity assays were determined by fluorescence microscopy and Trypan blue staining method, respectively. The formation of miR21a/CD‐PEI‐GQD Nanoplex with a decreased average size of 114 nm and a ζ‐potential (+36.1 mV) lower than CD‐PEI‐GQD nanocarrier by adding miR21a was confirmed at optimum C/P ratio =8.7. RT‐PCR revealed that miR21a/βCD‐PEI‐GQD Nanoplex significantly downregulated miR21 expression levels effectively. Overall, miR21a delivery using CD‐PEI‐GQD is presented as a novel trackable nanocarrier for cancer therapy.
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