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In this investigation, low molecular weight polyethyleneimine (LMW PEI; 1.8 kDa branched PEI) was conjugated to phathalated dextrin. The aim of this chemical modification was to decorate PEI molecules with a hydrophilic layer to improve its biophysical properties while the phthalic moiety may improve the hydrophilic‐hydrophobic balance of the final structure. The polymers were prepared at various conjugation degrees ranging from 6.5% to 16.5% and characterized in terms of biophysical characteristics as well as their gene transfer ability and cell‐induced toxicity. The results showed that dextrin‐phthalated‐PEI (DPHPEI) polymer was able to form nanoparticles with the size range of around 118–170 nm, with the zeta potential of 6.2–9.5 mV. DPHPEI polymers could increase the level of desired protein expression in the cells by up to three folds compared with unmodified LMW PEI while the cell viability of the modified polymers was around 80%. The result of this study shows a promising approach to improve the transfection efficiency of LMW PEI while maintaining its low toxic effects. [ABSTRACT FROM AUTHOR]

Co‐delivery of small chemotherapeutic molecules and nucleic acid materials via targeted carriers has attracted great attention for treatment of resistant tumors and reducing adverse effects. In this study, a targeted carrier for co‐delivery was prepared based on low‐molecular weight polyethylenimine (LMW PEI). Paclitaxel (PTX) was covalently conjugated onto PEI via a succinate linker. The PEI conjugate was decorated with L‐DOPA in order to target large neutral amino acid transporter‐1 (LAT‐1) that is over‐expressed on various cancer cells. This PEI conjugate was complexed with human ABCB1 shRNA plasmid to down‐regulate the expression of P‐glycoprotein, as one of the major efflux pumps inducing resistance against chemotherapeutics. The formation of PEI conjugate enhanced the solubility of PTX and resulted in the condensation and protection of plasmid DNA in nanosized polyplexes. The results of targeted delivery into the cells demonstrated that PEI conjugate transferred the payloads to the cells over‐expressing LAT‐1 transporter, while the biological effects on the cells lacking the transporter was negligible. Also, shRNA‐mediated down‐regulation of P‐gp led to the increase of toxic effects on the cells over‐expressing P‐gp. This study suggests a promising approach for co‐delivery of small molecules and nucleic acid materials in a targeted manner for cancer therapy. [ABSTRACT FROM AUTHOR]