PRECLINICAL REPORTSCodelivery of salinomycin and docetaxel using poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles to target both gastric cancer cells and cancer stem cellsLi, Lana,b; Cui, Dejunb; Ye, Liminb; Li, Yub; Zhu, Liyib; Yang, Lanqunb; Bai, Banjunb; Nie, Zhaob; Gao, Jiec; Cao, Yua Author Information aDepartment of Emergency, West China Hospital, Sichuan University, Chengdu bDepartment of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang cDepartment of Pharmacy, Second Military Medical University, Shanghai, China Correspondence to Yu Cao, MD, Department of Emergency, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, China Tel/fax: +86 28 85422288; e-mail: [email protected] Received April 16, 2017 Accepted June 13, 2017 Anti-Cancer Drugs: October 2017 - Volume 28 - Issue 9 - p 989-1001 doi: 10.1097/CAD.0000000000000541 Buy Metrics Abstract Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of ∼140 nm with a narrow size distribution, high drug loading, and sustained drug release. GC SCs were isolated by magnetic-activated cell sorting on the basis of CD44 expression as the CSC phenotype. CD44+ GC SCs showed the characteristics of CSCs, including increased SC gene expression, tumorsphere formation capacity, and tumorigenicity in nude mice. We found that both salinomycin and salinomycin-loaded nanoparticles (salinomycin-NPs) could selectively eradicate GC SCs, as reflected by reduced tumorsphere formation capacity and the frequency of CD44+ GC cells, whereas docetaxel and docetaxel-loaded nanoparticles (docetaxel-NPs) could significantly eradicate GC cells. In nude mice bearing GC xenografts, salinomycin-NPs and salinomycin significantly decreased the intratumor population of GC SCs. Notably, salinomycin-NPs combined with docetaxel-NPs suppressed tumor growth more effectively than did salinomycin combined with docetaxel, single salinomycin-NPs, or docetaxel-NPs. Therefore, salinomycin-NPs combined with docetaxel-NPs represent a promising strategy for the treatment of GC by eradicating both GC SCs and cancer cells. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.