The promotion of nanoparticle delivery to two populations of gastric cancer stem cells by CD133 and CD44 antibodies

[Display omitted] •Targeting two populations of gastric CSCs achieved better therapeutic efficacy compared with targeting one population.•CD44/CD133-ATRA-PLPN could increase the nanoparticle delivery to two populations of gastric CSCs.•CD44/CD133-ATRA-PLPN realized the targeted therapy of multiple gastric CSCs. Gastric cancer which starts from the stomach is a fatal cancer with poor prognosis around the world. The recurrence and metastasis of gastric cancer may be attributed to gastric cancer stem cells. It is recognized that cancer usually possesses multiple populations of distinct cancer stem cells with different phenotypes, thus it will be imperative to target more subsets of cancer stem cells instead of targeting only one population of cancer stem cells. It is generally accepted that both CD44 and CD133 are gastric cancer stem cells markers, we hereby developed CD44/CD133-ATRA-PLPN (CD44 and CD133 antibody-conjugated all-trans retinoic acid-loaded poly(lactide-co-glycolide)-lecithin-PEG nanoparticles) to target both CD133+ and CD44+ gastric cancer stem cells. In this study, the therapeutic effect of CD44/CD133-ATRA-PLPN against gastric cancer stem cells was investigated. The results presented here confirmed that CD44/CD133-ATRA-PLPN was efficiently and specifically delivered to CD44+ or CD133+ gastric cancer stem cells, resulting in enhanced growth inhibitory effect towards gastric cancer stem cells compared with single targeted and non-targeted nanoparticles. As far as we know, we firstly reported the promotion of nanoparticle delivery to two populations of gastric cancer stem cells by antibodies. Since cancer usually contains distinct populations of cancer stem cells with multiple phenotypes, our dual targeting nanoparticles constitute an effective drug delivery platform for targeting multiple populations of cancer stem cells within the cancer.