Synergistic co-administration of docetaxel and curcumin to chemoresistant cancer cells using PEGylated and RIPL peptide-conjugated nanostructured lipid carriers

초록

Background: A targeted co-administration system of docetaxel (DTX) and curcumin (CUR) using a PEG-modified RIPL peptide (IPLWPLRRRRRRRRC)-conjugated nanostructured lipid carrier (P/R-NLC) was constructed to exert synergistic anticancer effects against chemoresistant breast cancer. Results: DTX- or CUR-loaded NLCs and P/R-NLCs were prepared using the solvent emulsification-evaporation method. NLCs showed homogeneous spherical morphology with nano-sized dispersion (<210 nm) with zeta potential varying from - 16.4 to - 19.9 mV. DTX or CUR was successfully encapsulated in the NLCs: encapsulation efficiency (>95%); drug loading (8 - 18%). All NLC formulations were stable for 4 weeks under the storage conditions at 4 degrees C. Drug release was diffusion-controlled, revealing the best fit to the Higuchi equation. DTX- or CUR-loaded formulations showed dose-dependent cytotoxicity. The DTX/CUR combination (1:3 w/w) in P/R-NLC formulations exhibited the strongest synergism in both MCF7 and MCF7/ADR cells with combination index values of 0.286 and 0.130, respectively. Co-treatment with DTX- or CUR-P/R-NLCs increased apoptosis in both cell lines exhibited the superior synergistic inhibitory effect on MCF7/ADR three-dimensional spheroids. Finally, in OVCAR3-xenografted mouse models, co-treatment with DTX- or CUR-loaded P/R-NLCs significantly suppressed tumor growth compared to the other treatment groups. Conclusions: Co-administration of DTX/CUR (1:3 w/w) using P/R-NLCs induced a synergistic effect against chemoresistant cancer cells.

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