Anti-CD44 (aa 1-199) polyclonal antibody

This study aimed to present evidence that miR-7 inhibited the metastasis of breast cancer stem cells (BCSCs) and elucidated the mechanisms that have remained unknown. The samples collected from miR-7 agomir-treated, BCSC-driven tumors were subjected to a protein array to analyze the protein expression profiles. A dual-luciferase reporter and chromatin immunoprecipitation-PCR were used to validate and evaluate the molecular expressions of interest in the collected breast cancer tissues and cell lines. miR-7 overexpression affecting metastasis of BCSCs was further evaluated in mice. The endothelial cell-selective adhesion molecule (ESAM) was highly expressed in breast cancer tissues and in BCSC-driven xenografts. Results of the dual-luciferase reporter and chromatin immunoprecipitation-PCR indicated that the miR-7 mimic reduced RELA expression by directly targeting the 3' UTR of RELA to inhibit ESAM expression in MDA-MB-231 cells. Moreover, the expression levels of RELA, CD44, and ESAM were significantly decreased in lentivirus (Lenti)-miR-7-BCSC-driven xenografts compared with the control xenografts, accompanied with an increase in E-cadherin and a decrease in vimentin expression, as well as reduction in tumor growth and metastasis to lungs. Our data demonstrated that miR-7 overexpression reduced the metastasis of BCSCs via inhibiting ESAM, suggesting that ESAM could be a potential target for breast cancer therapy.

Utilizing intratumoral iron mediated Fenton reaction to induce cancer cells destruction, chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the CDT efficacy is severely restrained by insufficient endogenous H2O2 and catalytic ferrous ions in tumor site. Herein, based on innovative small molecule prodrug design concept, an acid-labile ferrocene-modified cinnamaldehyde prodrug (Fc-CA) was first synthesized. Skillfully combining ROS-generator CA with Fenton catalyst Fc in its molecular structure, Fc-CA could synchronously elevate H2O2 level and catalytic iron amount for enhanced CDT efficacy. Then, hydrophobic Fc-CA was efficiently encapsulated into hydrophilic cyclodextrin-modified hyaluronic acid conjugate (HA-CD) via host-guest interactions, to spontaneously form pH/redox dual-responsive supramolecular catalytic nanoreactor (HA-CD/Fc-CA NPs). The nanoreactor with high drug loading and stability, excellent catalytic activity and tumor specificity could preferentially accumulate in tumor tissues via EPR effect and CD44 receptor-mediated internalization. Through the cleavage of acid-labile hydrazone bond under acidic lysosome environments, the nanoreactor would be dissociated and release pre-protected CA for reinforced oxidation therapy and amplified H2O2 level, which would in turn react with Fc through cascaded Fenton reaction, to generate highly cytotoxic center dot OH for enhanced cancer killing in a positive feedback process. Both in vitro and in vivo results verified excellent cascade-amplifying therapeutic performance and favorable biocompatibility of this nanoreactor. This study provides an innovative strategy for exploiting versatile organic therapeutic nanoplatforms, simultaneously activating tumor-specific oxidative stress amplification and cascaded enhanced Fenton reaction for superior cancer therapy with excellent biosafety.