Multidimensional Quantitative Measurement of Cancer Chemoresistance through Differential ZIF-8 Nanoparticle Cellular Retention

Abstract

Chemoresistance of cancer cells is conventionally quantified by half-maximal inhibitory concentration (IC 50 ) or multidrug resistance gene 1 (MDR1) values, but these metrics can only reflect the overall drug resistance level of a cancer cell line. Meanwhile, the multidimensional evaluation of both the heterogeneity in a cell line and the drug resistance degree of each cell still presents a daunting challenge. We report here that the cellular heterogeneity, cellular cross contamination, and the proportion of chemoresistant cancer cells can be visualized via flow cytometry through the differential cellular retention of fluorescent ZIF-8 nanoparticles. In addition, we show that the degree of drug resistance exhibited by each cell subpopulation can be quantified by differing fluorescence of the drugresistant and drug-sensitive cells in the corresponding flow cytometry profile, and the quantified metric S is highly consistent with the MDR1 expression results. Importantly, this novel strategy is applicable to various cancer cell lines, thus demonstrating a universal diagnosis platform for multidimensional, quantitative, and highly efficient diagnosis of cancer chemoresistance.

Single-Cell Diagnosis of Cancer Drug Resistance through the Differential Endocytosis of Nanoparticles between Drug-Resistant and Drug-Sensitive Cancer Cells

“…In our previous work, 72 we have described the measurement of cancer chemoresistance of drug-resistant cancer cell models through differential ZIF-8 nanoparticle cellular retention in detail, and here we subsequently evaluated the clinical applicability of this ZNP-based diagnosis strategy using clinical samples obtained from lung cancer patients. The cellular suspensions from two pleural effusions and two surgically removed tumor specimens were pretreated to remove nontumor cells and then incubated with ZNPs (Figure 6A).…”