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Cancer stem cells (CSCs) are the subpopulation of tumor cells with the properties of tumorigenesis, multilineage differentiation potential and self-renewal, which is the driving force of tumor recurrence and metastasis. However, targeting CSCs is still the main challenge in cancer therapy due to their rapid growth and fast mutation rate. Herein, we developed a simple strategy of photodynamic therapy (PDT) targeting CSCs, dependent on much more abundant ribosomes in CSCs. The interactions between positively charged nanoparticles with negatively charged nucleic acids architectures in cancer cells could lead ribosomes targeting as well as CSCs targeting. The co-assembly of simple amino porphyrin (m -TAPP) with short peptide (Fmoc-L 3 -OMe) formed nanoparticles (NPs) with good biocompatibility and photoactivity, became positively charged due to low pH value of tumour microenvironment, and efficiently accessed cancer cell ribosome, approached cancer cell nuclei, therefore enriched in the fast-amplifying CSCs. The inhibitive effect on CSCs by m -TAPP assemblies was verified by the significant reduction of CSCs markers CD44, CD133 and ribosome amount in cancer cells and tissues. Upon light irradiation, the NPs induced ROS generation to provoke destructive cancer cell ribosome damage and subsequent apoptosis to prevent tumor growth markedly. Based on the assemblies of small organic molecules, our study not only achieves ribosome degradation induced cancer cells apoptosis, but also indicates new possibility of performing CSCs targeting PDT. [ABSTRACT FROM AUTHOR]

Gastric cancer stem cells (GCSCs) have been used as a therapeutic target. This study aims to estimate the role of miR-98-5p (termed miR-98) in the development of GCSCs. The expression of miR-98 in CD44+ GCSCs was verified by RT-PCR. The miR-98 was overexpressed in CD44+ GCSCs by Lentivirus. The ability of self-renewal, invasion, chemoresistance and tumorigenicity was detected in vitro or in vivo after overexpression of miR-98. The target genes of miR-98 were predicted and verified by luciferase reporter assays. The effects miR-98 / BCAT1 signaling on the chemoresistance and tumorigenicity of CD44+ GCSCs were investigated in a xenograft model by rescue experiments. We have shown that miR-98 was decreased in CD44+ GCSCs. The overexpression of miR-98 could inhibit the expression of stem-related genes and the ability of self-renewal, invasion, and tumorigenicity of GCSCs. Also, we found that miR-98 overexpression enhances the sensitivity to cisplatin treatment in vitro. Using a xenograft model, we showed that miR-98 overexpression reversed paclitaxel resistance to CD44+ GCSCs. Finally, we found that branched-chain aminotransferases 1 (BCAT1) is a target gene of miR-98. Overexpressed BCAT1 reversed xenograft tumor formation ability and attenuated the paclitaxel chemosensitivity induced by miR-98 downregulation. Furthermore, BCAT1 restoration affected the expression of invasion and drug resistance-related genes. This study revealed miR-98 inhibits gastric cancer cell stemness and chemoresistance by targeting BCAT1, suggesting that this miR-98 / BCAT1 axis represents a potential therapeutic target in gastric cancer. [ABSTRACT FROM AUTHOR]