journal article·2023-10-10

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

Lingshan Liu, Qiurui Zhang, Chenglong Wang, Heze Guo, Vincent Mukwaya, Rong Chen, Yichun Xu, Xiaohui Wei, Xiaoyan Chen, Sujiang Zhang, Min Zhou, Hongjing Dou

ACS Nano· Volume 17· Issue 19
Publisher page

Abstract

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO 2 nanoparticles (SNPs), organic PS- co -PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle–cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.
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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Nanoparticle-Based Drug Delivery · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China

Zhangjiang Institute for Advanced Study (ZIAS), Shanghai Jiao Tong University, 429 Zhangheng Road, Shanghai 201203, China

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China

Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China

Shanghai Biochip Co. Ltd. and National Engineering Center for Biochip at Shanghai, 151 Libing Road, Shanghai 201203, China

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China

Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China

Funding

Shanghai Jiao Tong University · National Key Research and Development Program of China · Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning · Science and Technology Commission of Shanghai Municipality · National Natural Science Foundation of China · Research and Exchange Project in the Field of Medical and Health

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