Journal
JOURNAL OF CONTROLLED RELEASE
Volume 330, Issue -, Pages 1106-1117Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2020.11.015
Keywords
Multidrug resistance; Cancer stem cells-targeted nanocarriers; Co-delivery; P-glycoprotein inhibitor; 3D mammosphere suspension culture
Funding
- China Scholarship Council
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The study developed CSCs-specific targeted mSiO(2)-dPG nanocarriers for co-delivery of DOX and Tar, which significantly enhanced the chemotherapeutic efficacy against breast CSCs by suppressing stemness-associated gene expression and tumorspheres' formation ability.
Multidrug resistance (MDR) of cancer stem cells (CSCs) is a major hurdle to chemotherapy, and it is very important to develop CSCs-specific targeted nanocarriers for the treatment of drug resistant CSCs. In this work, we developed CSCs-specific targeted mSiO(2)-dPG nanocarriers simultaneous delivery chemotherapy drug DOX along with the P-glycoprotein (P-gp) inhibitor tariquidar (Tar) for enhanced chemotherapy to overcome MDR in breast CSCs. The mSiO(2)-dPG nanocarriers possess a high loading capability, excellent pH stimuli-responsive performance, and good biocompatibility. With the help of CSCs-specific targeting and P-gp inhibitor Tar, the accumulation of DOX delivered by the mSiO(2)-dPG nanocarriers could be greatly increased in drug resistant three-dimensional mammosphere of breast CSCs, and the chemotherapeutic efficacy against breast CSCs was enhanced. Moreover, the expression of stemness-associated gene and tumorspheres' formation ability was also significantly suppressed, which indicates the excellent capability for overcoming MDR of breast CSCs. Taken together, we developed a CSCs-specific targeted mSiO(2)-dPG nanocarriers for co-delivery DOX and Tar, which provide a promising approach to effectively eliminate the CSCs and overcome the MDR of breast CSCs.
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