pH-responsive cocktail drug nanocarriers by encapsulating paclitaxel with doxorubicin modified poly(amino acid)

We design a pH-responsive cocktail nanocapsule with a suitable size (around 100 nm) via the assembly of doxorubicin (DOX) modified poly(amino acid). Paclitaxel (PTX) is successfully encapsulated in the hydrophobic cavity of the nanocapsules through a non-covalent interaction between PTX and the DOX modified poly(amino acid). Guided by the surface bioconjugated Arg-Gly-Asp (RGD) moieties, a target peptide, nanocapsules are targeted to and uptaken by cancer cells. These nanocapsules are stable under normal physiological pH conditions (pH 7.4) and drug release can be triggered by the relatively low pH (5.0) in cancer cells. Moreover, the drug release can be tracked via the recovered red fluorescence of DOX due to the relief from the self-quenching state as a result of nanocapsule disruption under acidic conditions. The in vitro test results undoubtedly confirm the RGD-mediated synergetic therapeutic efficacy of these cocktail drug nanocapsules. This research paves a new way for the fabrication of smart nanocapsules for cocktail drug delivery.