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Published on: May 22, 2020
Biomarkerless targeting and photothermal cancer cell killing by surface-electrically-charged superparamagnetic Fe3O4
Xiao Han1, Zicheng Deng1, Zi Yang1
1School of Materials Science and Engineering, Tongji University, Shanghai 200092, PR China and The Institute for Translational Nanomedicine, Shanghai East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, PR China. yilongwang@tongji.edu.cn donglu.shi@uc.edu.
Abstract:
A major challenge in cancer therapy is localized targeting of cancer cells for maximum therapeutic effectiveness. However, due to cancer heterogeneities, the biomarkers are either not readily available or specific for effective targeting of cancer cells. The key, therefore, is to develop a new targeting strategy that does not rely on biomarkers. A general hallmark of cancer cells is the much increased level of glycolysis. The loss of highly mobile lactate from the cytoplasm inevitably removes labile inorganic cations to form lactate salts and acids as part of the lactate cycle, creating a net of negative surface charges. This net of negative charges on cancer cell surfaces biophysically distinguishes themselves from normal cells. In this study, cancer cells are targeted by using positively-charged, fluorescent, superparamagnetic Fe3O4-composite nanoparticles. The positively-charged Fe3O4 composite nanoparticles bind predominantly to cancer cells due to their negatively-charged surfaces. Upon electrical-charge-mediated Fe3O4 nanoparticle binding onto cancer cells, irradiation by using an 808 nm laser is subsequently applied to induce photothermal hyperthermia that kills the cancer cells directly. The negatively-charged composite nanoparticles are found, however, not to target and bind the cancer cells due to the electrostatic repulsive force between them. This unique strategy paves a new path for effective targeting and direct cancer cell killing without relying on any biomarkers and anticancer drugs.
Insights
This study introduces a novel cancer therapy using positively charged nanoparticles that target cancer cells via their negative surface charge. This method enables biomarker-free, drug-free cancer cell destruction through photothermal hyperthermia.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Targeted cancer therapy faces challenges due to tumor heterogeneity and lack of specific biomarkers.
- Cancer cells exhibit increased glycolysis, leading to a net negative surface charge distinct from normal cells.
- Developing biomarker-independent targeting strategies is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a novel cancer cell targeting and destruction strategy independent of biomarkers.
- To investigate the use of positively charged superparamagnetic iron oxide (Fe3O4)-composite nanoparticles for cancer cell targeting.
- To evaluate photothermal hyperthermia as a direct cancer cell killing mechanism mediated by these nanoparticles.
Main Methods:
- Synthesized positively-charged, fluorescent, superparamagnetic Fe3O4-composite nanoparticles.
- Exploited the negative surface charge of cancer cells (due to lactate accumulation) for electrostatic nanoparticle binding.
- Applied 808 nm laser irradiation for photothermal hyperthermia-induced cancer cell death.
- Utilized negatively-charged nanoparticles as a control to confirm charge-mediated targeting.
Main Results:
- Positively-charged Fe3O4 nanoparticles selectively bound to cancer cells with negative surface charges.
- Negatively-charged nanoparticles did not bind to cancer cells due to electrostatic repulsion.
- Photothermal hyperthermia effectively induced direct cancer cell killing upon nanoparticle binding.
- The strategy demonstrated successful, biomarker-free, and drug-free cancer cell targeting and destruction.
Conclusions:
- Positively-charged Fe3O4-composite nanoparticles offer a promising approach for targeted cancer therapy.
- Electrostatic interaction based on cancer cell surface charge is an effective targeting mechanism.
- This novel strategy enables direct cancer cell killing via photothermal hyperthermia without biomarkers or drugs.
