Abstract
Abstract Lung adenocarcinoma (LAC) has been clinically realized to be one of the most deadly malignant tumors with relatively low in 5-year survival rate. High recurrence rates and drug-resistance potential have been reported in LAC even after completion of combined therapy. Herein we demonstrate that cisplatin treatment selecting for resistance with high self-renewal and invasive capabilities in cisplatin-resistant LAC cell (CisR-LAC). For overcoming the multi-drug resistance (MDR) in CisR-LAC, we designed a multifunctional nanocarrier with enhanced targeting ability and inhibition of MDR inhibition in CisR-LAC. The platform provide a high anti-MDR efficacy via a facile synthesis scheme using an amphiphilic chitosan to encapsulate a demethoxylcurcumin (DMC), as a core phase, following surface modification of an anti-EGFR layer, forming a CHC-DMC/anti-EGFR core-shell nanostructure. Experimental outcomes revealed an enhanced therapeutic efficacy of the DMC, forming DMC nano-precipitates in lysosome and endosome, as a result of efficient cellular endocytosis of the core-shell nanoparticles, by a synergistic action of both MDR inhibition and efficacious cell killing. Animal study showed a significant therapeutic efficacy against CisR-LAC-xenograft lung tumor using the core-shell nanocarriers, by a reduction of as high as 5-folded tumor volume compared with control groups. This result indicated the multi-therapeutic efficacy of the multifunctional CHC-DMC/anti-EGFR core-shell nanoparticle, providing a potential capability in anti-MDR LAC for better clinical translation. Note: This abstract was not presented at the meeting. Citation Format: Shih-Hwa Chiou. Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4373. doi:10.1158/1538-7445.AM2015-4373
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