Fluorescent Polysaccharide Nanogels for the Detection of Tumor Heterogeneity in Drug-Surviving Cancer Cells

Abstract

Tumor metastasis, recurrence, and drug resistance have been associated with tumor heterogeneity, and thus the identification of tumor heterogeneity has great significance in medicine. The approach provides a way to identify and isolate various cell subtypes from drug-surviving ovarian cancer cells, by synthesizing a series of polysaccharide nanogels and using them in flow cytometry analysis. The results show that the drug-surviving OVCAR-3 cells that are subjected to paclitaxel intervention comprise various cell subtypes, including drug-resistant and non-drug-resistant cell subtypes. Besides, there are significant differences between the drug-resistant cell subtype and non-drug-resistant cell subtype in terms of their migration and invasion behavior. In addition, the phenotype switch genes are detected by mRNA sequencing, and it is found that different subtypes show significant genetic differences with regard to their drug resistance, metastasis, and proliferation. In particular, modifying polysaccharide nanogels with lipids can promote the uptake of nanogels by drug-resistant cells, and thus the lipid modification can enhance the effectiveness of a chemotherapy drug carrier against drug-resistant cells. These studies reveal the heterogeneity of drug-surviving tumor cells, as well as the significant differences in drug-resistance, migration, and invasion capabilities of different subtypes, and demonstrate a way to overcome drug resistance.