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. 2018 Nov 6;13:7135–7153. doi: 10.2147/IJN.S182445

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© 2018 Li et al. This work is published and licensed by Dove Medical Press Limited

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Schematic diagram of the self-assembly DHP nanocomplexes to enhance the antitumor activity.

Notes: DHP nanocomplexes accumulate in the tumor via the EPR effect and actively target tumor cells due to its high-affinity interactions with expressed integrin ανβ3. The nanocomplexes enter the cell by endocytosis, then rapidly escape from endosomes by the “proton sponges” mechanism. PEG chains can be cleaved from PAMAM due to the high concentration of GSH in the cytoplasm. Finally, the plasmid DNA is delivered to the nucleus with the help of HMGB1 due to its nuclear locating ability.

Abbreviations: DHP, pDNA/HMGB1/PSSP-RGD; EPR, enhanced permeability and retention effect; GSH, glutathione; HMGB1, high mobility group box 1; PAMAM, polyamidoamine; PEG, polyethylene glycol; PSSP-RGD, PAMAM-SS-PEG-arginine-glycine-aspartate.