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Site-Specific Location of Black Phosphorus Quantum Dot Cluster-Based Nanocomplexes for Synergistic Ion Channel
Yafeng Wu1, Zhaoyan Tian2, Zhi Wang3
1Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
Abstract:
The spatiotemporal regulation of ion transport in living cell membrane channels has immense potential for providing novel therapeutic approaches for the treatment of currently intractable diseases. So far, most strategies suffer from uncontrolled ion transport and limited tumor therapy effects. On the premise of low toxicity to healthy tissues, enhancing the degree of ion overloading and the effect of tumor treatment still remains a challenging concern. Herein, an innovative strategy for synergistic ion channel therapy and hypoxic microenvironment activated chemotherapy is proposed. Biocompatible AQ4N/black phosphorus quantum dot clusters@liposomes (AQ4N/BPCs@Lip) nanocomplexes are site-specifically immobilized on the living cell membrane by a metabolic labeling strategy, eliminating the need for modifying or genetically encoding channel structures. Ascribing to the localized temperature increase of BPCs under NIR light irradiation, Ca2+ overinflux can be remotely controlled and the overloading degree was increased; moreover, the local released AQ4N can only be activated in the tumor cell, while it has no toxicity to normal cells. Compared with single intracellular Ca2+ overloading, the tumor cell viabilities decrease 2-fold with synergetic Ca2+ overloading-induced ion channel therapy and hypoxic microenvironment activated chemotherapeutics. Our study demonstrates the example of a remote-controlled ion influx and drug delivery system for tumor therapy.
Insights
This study introduces a novel nanocomplex for synergistic cancer therapy. It combines remote-controlled calcium ion overloading with chemotherapy activated by the tumor
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Spatiotemporal regulation of ion transport offers therapeutic potential but faces challenges in controlling ion flux and tumor effects.
- Existing strategies often lack precise control over ion transport and exhibit limited efficacy in tumor treatment.
- Enhancing ion overloading and therapeutic outcomes while maintaining low toxicity to healthy tissues remains a significant challenge.
Purpose of the Study:
- To propose an innovative strategy for synergistic ion channel therapy and chemotherapy activated by the hypoxic tumor microenvironment.
- To develop biocompatible nanocomplexes for site-specific immobilization on cell membranes without genetic modification.
- To achieve remote-controlled ion influx and targeted drug activation for enhanced tumor treatment.
Main Methods:
- Fabrication of AQ4N/black phosphorus quantum dot clusters@liposomes (AQ4N/BPCs@Lip) nanocomplexes.
- Site-specific immobilization of nanocomplexes on living cell membranes via metabolic labeling.
- Remote control of Ca2+ overinflux using near-infrared (NIR) light irradiation to induce localized temperature increase in black phosphorus quantum dots.
- Hypoxic microenvironment-activated chemotherapy using AQ4N, which is selectively activated in tumor cells.
Main Results:
- AQ4N/BPCs@Lip nanocomplexes were successfully immobilized on cell membranes without genetic modification.
- NIR light irradiation enabled remote and controlled Ca2+ overinflux, increasing the overloading degree.
- AQ4N was selectively activated in tumor cells, demonstrating no toxicity to normal cells.
- Synergistic therapy combining Ca2+ overloading and chemotherapy resulted in a 2-fold decrease in tumor cell viability compared to single Ca2+ overloading.
Conclusions:
- The developed AQ4N/BPCs@Lip nanocomplexes provide a promising platform for synergistic cancer therapy.
- The strategy enables remote-controlled ion influx and targeted drug delivery, enhancing therapeutic efficacy.
- This approach offers a potential solution for treating intractable diseases with improved tumor treatment effects and low toxicity.
