Synergistic co-administration of docetaxel and curcumin to chemoresistant cancer cells using PEGylated and RIPL peptide-conjugated nanostructured lipid carriers
Chang‐Hyun Kim, Byoung Deok Kim, Tae Wha Lee, Hyeon Kyun Kim, Min Jeong Lyu, Young In Yoon, Yoon Tae Goo, Myung Joo Kang, Sang Kil Lee, Young Wook Choi
Abstract
Abstract Background A targeted co-administration system of docetaxel (DTX) and curcumin (CUR) using a PEG-modified RIPL peptide (IPLVVPLRRRRRRRRC)-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 °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. Graphical Abstract