Novel Non-Viral Vectors Based on Pluronic ® F68PEI with Application in Oncology Field

• Published in: Polymers Vol. 14; no. 23; p. 5315
• Main Authors: Silva, Inês, Domingues, Cátia, Jarak, Ivana, Carvalho, Rui A, Cordeiro, Rosemeyre A, Dourado, Marília, Veiga, Francisco, Faneca, Henrique, Figueiras, Ana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: Biological activity; Cancer; cancer therapy; Cellulose acetate; Copolymers; Ethanol; Ethylenediaminetetraacetic acid; Gene therapy; Infection; NMR; non-viral vectors; Nuclear magnetic resonance; Optimization; Particle size; pDNA; Photon correlation spectroscopy; Pluronics; Polyethyleneimine; polyethylenimine; Polymers; Selectivity; Spectrum analysis; Squamous cell carcinoma; Portugal; St Louis Missouri; France; United States > US; Germany; cancer therapy; Pluronics; pDNA; non-viral vectors; polyethylenimine
• ISSN: 2073-4360; 2073-4360
• DOI: 10.3390/polym14235315

Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1−100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.