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A Sensor Array Composed of Organelle-Targeting Fluorescent Probes and Polydopamine Particles for Deep
Guoyang Zhang1,2, Guanghui Zhu2, Jiguang Li1
1State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.
Abstract:
Lung cancer, a leading cause of global cancer-related mortality, predominantly features nonsmall cell lung cancer (NSCLC), constituting 80% of all lung malignancies. Despite chemotherapy being the primary NSCLC treatment, the emergence of drug resistance poses a significant challenge. Identifying drug-resistant cells and characterizing the resistance type is crucial for guiding clinical interventions in NSCLC. The homogeneity of drug-sensitive/resistant cancer cells presents a challenge in their identification as well as in distinguishing tumor slices. Organelles, pivotal for cellular function, exhibit notable variations in the microenvironment among diverse cell types. In this work, three organelle-targeting nanoparticles, composed of fluorescent probes and polydopamine particles, collectively formed PPTA-SA (an organelle-targeting sensor array) for imaging NSCLC cells and tumor slices. With a deep learning network, PPTA-SA could be used for identification of drug-resistant lung cells and tumors. The achieved identification accuracy for drug-resistant NSCLC cells and NSCLC tumor slices was more than 99%. Moreover, the multiorganelle targeting photothermal therapy demonstrated superior tumor ablation effects compared to conventional single-organelle targeting photothermal therapy. The combination of fluorescent probes and polydopamine not only served as a valuable tool for drug-sensitive/resistant NSCLC identification but also facilitated photothermal therapy with enhanced effects.
Insights
This study introduces PPTA-SA, an organelle-targeting sensor array, to identify drug-resistant lung cancer cells and tumors with over 99% accuracy. It also enhances photothermal therapy for improved tumor ablation.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality, with drug resistance limiting treatment efficacy.
- Accurate identification of drug-resistant NSCLC cells and tumors is critical for personalized treatment strategies.
- Organelle variations within the tumor microenvironment offer potential targets for diagnostic and therapeutic interventions.
Purpose of the Study:
- To develop an organelle-targeting sensor array (PPTA-SA) for identifying drug-resistant NSCLC cells and tumors.
- To evaluate the diagnostic accuracy of PPTA-SA using a deep learning network.
- To investigate the therapeutic potential of multiorganelle-targeting photothermal therapy (PTT) for NSCLC ablation.
Main Methods:
- Fabrication of PPTA-SA using fluorescent probes and polydopamine nanoparticles targeting specific organelles.
- Application of a deep learning network for analyzing PPTA-SA imaging data to distinguish drug-sensitive and drug-resistant NSCLC.
- Comparison of multiorganelle-targeting PTT with single-organelle-targeting PTT for tumor ablation efficacy.
Main Results:
- PPTA-SA achieved over 99% accuracy in identifying drug-resistant NSCLC cells and tumor slices.
- Multiorganelle-targeting PTT demonstrated significantly enhanced tumor ablation compared to single-organelle PTT.
- The combined fluorescent probe and polydopamine system effectively identified drug resistance and facilitated PTT.
Conclusions:
- PPTA-SA is a highly accurate tool for identifying drug-resistant NSCLC, aiding in clinical decision-making.
- Multiorganelle-targeting PTT offers a promising therapeutic strategy with improved efficacy for NSCLC.
- The integration of advanced imaging and targeted therapy represents a significant advancement in NSCLC management.
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