Ionic-crosslinked polysaccharide/PEI/DNA nanoparticles for stabilized gene delivery

In gene therapy, the stability of gene delivery system is essential during the systemic circulation. To improve the stability of PEI/DNA complexes, sodium alginate (Alg) was chosen as the optimal shielding material from four different polysaccharides. Then Alg/PEI/DNA complexes were further crosslinked by calcium ions (Ca2+) to form Ca2+/(Alg/PEI/DNA) nanoparticles. Compared to PEI/DNA complexes and Alg/PEI/DNA complexes, Ca2+/(Alg/PEI/DNA) nanoparticles exhibited enhanced stability, which was confirmed by the in vitro and in vivo evaluations. Furthermore, the pharmacokinetic study indicated that Ca2+/(Alg/PEI/DNA) nanoparticles exhibited longer circulation time in blood, which would be beneficial to the enhanced permeability and retention (EPR) effect of nanoparticles and could realize improved nanoparticles accumulation at tumor site. Overall, the Ca2+/(Alg/PEI/DNA) nanoparticles based on alginate shielding and Ca2+ crosslinking might be a promising platform in gene delivery and tumor treatment.