Enhanced gene transfection ability of sulfonylated low-molecular-weight PEI and its application in anti-tumor treatment†

Abstract

With the continuous progress of nanotechnology in the field of tumor vaccines, immunotherapy has been regarded as one of the most powerful approaches for cancer treatment. Currently, DNA vaccines are used to efficiently deliver plasmids encoding tumor-associated antigens to antigen-presenting cells (APCs) and enhance the activation of immune cells. In this work, a series of aromatic sulfonyl small-molecule-modified polymers R-P based on low-molecular-weight polyethylenimine (PEI) were prepared, and their structure–activity relationship was studied. Among them, Ns-P with high transfection efficiency and low toxicity was applied to deliver antigen ovalbumin (OVA)-encoded plasmid DNA to APCs for triggering the immune activation of dendritic cells (DCs). It was also found that Ns-P could be used as an immune adjuvant to activate the STING pathway in DCs, integrating innate stimulating activity into the carrier to enhance antitumor immunity. Moreover, the modification of Ns-P/pOVA complexes with oxidized mannan could not only improve the biocompatibility of the complex, but also enhance the uptake of DCs, further inducing OVA antigen presentation and immune stimulation. In vivo antitumor assays indicated that Ns-P/pOVA/Man immunization could inhibit the growth of OVA-expressing E.G7 tumors in C57BL/6 mice. These results demonstrated that Ns-P/pOVA/Man is promising for gene delivery and immunotherapy application.