Poly(l-aspartic acid) nanogels for lysosome-selective antitumor drug delivery

Advanced materials that have controllable pH-responsive properties when submerged in the lysosome have a great potential in intracellular drug delivery. We developed novel poly(l-amino acid) nanogels that were prepared by a facile cross-linking of poly[l-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol)-maleimide [poly(l-Asp-g-DEAP)-b-PEG-Mal] and poly(l-aspartic acid-g-ethyl thiol)-b-PEG [poly(l-Asp-SH)-b-PEG] in an oil/water emulsion condition. Interestingly, these nanogels (∼125 nm in diameter) modulated volume expansion (∼375 nm in diameter) in a lysosomal pH (∼pH 5.0) due to an extensive proton absorption of DEAP at a low pH, which mediated lysosome swelling and the subsequent lysosome destabilization. In the in vitro tumor cell cytotoxicity test, they encouraged tumor cell death, probably owing to the leakage of lysosomal enzymes. Furthermore, encapsulating antitumor drug (e.g., doxorubicin, DOX) into these nanogels enhanced tumor cell cytotoxicity. We conclude that this nanogel system will have great potential for tumor therapy.

Figure optionsDownload as PowerPoint slideHighlights
► Poly(l-aspartic acid) derivative nanogels exhibited an advanced capacity for pH-triggered volume change.
► Encapsulating antitumor drug into these nanogels enhanced tumor cell cytotoxicity.
► These nanogels will have great potential for tumor therapy.