FIGURE 3.

Nanostructured lipid carrier (NLC) system for the pulmonary codelivery of paclitaxel (TAX) and siRNAs for resistance suppression to treat lung cancer. (a) Illustration of the NLC system, showing drugs loaded in the core (TAX), siRNAs complexed to cationic heads groups of the lipid particle (DOTAP), and lung cancer targeting moiety, luteinizing hormone-release hormone (LHRH) conjugated to DSPE-PEG on the surface. (b) Cell viability of A549 human lung adenocarcinoma cells after 48 hr incubation with blank NLC and PEGylated NLC, showing great biocompatibility of the carrier with increased safety after surface decoration with PEG. (c) in vitro cytotoxicity of the TAX-loaded NLCs and free TAX against A549 cells; the NLC systems showed enhanced cytotoxicity (lower IC50 value) compared to free TAX, where the addition of resistance suppressing siRNAs on the surface even further enhanced cytotoxic activity. (d) in vivo distribution of fluorescently-labeled (Cy5.5 dye) NLCs in mice after IV injection (left) and inhalation (right), showing increased accumulation and retention in lungs from pulmonary delivery. (e) Distribution of fluorescently-labeled NLCs in mice lungs bearing A549 tumors, highlighting improved targeting to tumor tissues by LHRH. (f) Bright-field and fluorescence microscope images of tumor tissues of mice treated with Cy5.5-loaded LHRH-NLCs, showing improved tumor targeting and retention with minimal accumulation in healthy lung tissues. (g) Tumor volume changes in mice after the beginning of treatment with repeated treatments every 3–5 days (x-axis), emphasizing the enhanced antitumor efficacy of LHRH-NLC-TAX-siRNAs system (1, untreated mice; 2, inhaled LHRH-NLC; 3, IV injected TAX; 4, inhaled LHRH-NLC-TAX; 5, inhaled LHRH-NLC-TAX-siRNAs). (Reprinted with permission from Taratula et al. (2013). Copyright 2013 Elsevier)