Scientists develop multifunctional nano platforms to provide effective methods for the treatment of triple negative breast cancer

Tech 2023-07-05 08:08:47 Source: Network

Recently, researchers from the National Nanometer Center developed a multifunctional nano platform (MTO micelles) based on the clinical chemotherapy drug Mitoxantrone, which enables the realization of synergistic mild photothermal chemotherapy.In the study, they encapsulated MTO in nano micelles, effectively inhibiting the growth of triple negative breast cancer

Recently, researchers from the National Nanometer Center developed a multifunctional nano platform (MTO micelles) based on the clinical chemotherapy drug Mitoxantrone, which enables the realization of synergistic mild photothermal chemotherapy.

In the study, they encapsulated MTO in nano micelles, effectively inhibiting the growth of triple negative breast cancer. This mild photothermal chemotherapy formula can down regulate the expression of HSP70, thereby increasing the DNA damage of tumor cells, thus providing a simple and effective method for the treatment of triple negative breast cancer.

Recently, the related paper titled "DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild PhotothermalChemotherapy for TNBCvia Decreasing Heat Shock Protein 70 Expression" was published onAdvancedScienceGo up [1].

Zuqin Chen is the first author, and Li Fangzhou, Professor Leung Hing Kit of the National Nanotechnology Center and Professor Xiao Yueyong of the 301 Hospital are the co corresponding authors.

| AdvancedScience

It is reported that triple negative breast cancer is a subtype of breast cancer with high intractability and poor prognosis, and there is still a lack of effective Targeted therapy. Therefore, they want to explore a new treatment strategy that utilizes nanotechnology to assist photothermal therapy and achieve the synergistic effect of mild photothermal chemotherapy.

Later, they chose MTO as a chemotherapy drug and photothermal conversion agent because of its excellent near-infrared absorption and anti-tumor activity, and it has been used in clinical treatment.

In the study, the research team designed a series of experiments, including the preparation and characterization of MTO micelles, the in vitro and in vivo photothermal conversion efficiency of MTO micelles, the in vitro and in vivo drug release kinetics of MTO micelles, the in vitro and in vivo cytotoxicity and anti-tumor effects of MTO micelles, the in vivo drug distribution and metabolism of MTO micelles, and the mild photothermal chemotherapy synergistic mechanism of MTO micelles.

Subsequently, they analyzed and discussed the experimental data and results, and found that MTO micelles have the following characteristics:

Firstly, MTO micelles have a smaller particle size (about 100nm), higher drug loading capacity (about 20%), and better stability;

Thirdly, MTO micelles can accumulate at tumor sites through enhanced permeation and retention effects, and can release more MTO under mild high temperatures;

Fourthly, MTO micelles can achieve synergistic mild photothermal chemotherapy, which can improve the apoptosis rate and necrosis rate of triple negative breast cancer cells, thereby inhibiting the growth of triple negative breast cancer tumors;

Fifthly, MTO micelles can enhance DNA damage and lead to downregulation of HSP70 expression, which in turn can weaken the heat tolerance of tumors and enhance the effectiveness of mild photothermal therapy;

Sixth, MTO micelles have good biocompatibility and biodegradability, and can be metabolized and excreted in the body.

In addition, the enhancement of DNA damage leads to a downregulation of the expression of heat shock protein 70 (HSP70), which in turn weakens the tumor's heat tolerance and enhances the effectiveness of mild photothermal therapy.

The above findings reveal the synergistic mechanism of MTO micelles in mild photothermal chemotherapy, and provide a new idea for the treatment of triple negative breast cancer.

Secondly, this work addresses two challenges currently faced by nanotechnology assisted photothermal therapy: firstly, the heat resistance caused by photothermal therapy limits the therapeutic effect of photothermal therapy; Secondly, there is uncertainty in the physiological metabolism of existing photothermal nanoparticles, which affects their clinical application.

In this study, MTO micelles were used to achieve mild photothermal chemotherapy, which not only avoided normal tissue damage caused by high temperature, but also reduced the production of heat resistance.

At the same time, MTO micelles are prepared based on clinical drug MTO and have good biocompatibility and biodegradability, which is beneficial for metabolism and excretion in vivo.

Due to the fact that MTO micelles are prepared based on clinical chemotherapy drug MTO, they can achieve mild photothermal chemotherapy, avoiding normal tissue damage caused by high temperature and reducing the production of heat resistance. In several years, this achievement has the following potential applications:

First, it can be used for the treatment of triple negative breast cancer. Triple negative breast cancer is a subtype of breast cancer with high intractability and poor prognosis. At present, there is no effective Targeted therapy. MTO micelles can achieve synergistic mild photothermal chemotherapy, thereby improving the cure rate and survival rate of triple negative breast cancer patients.

Secondly, it can be used for the treatment of other types of cancer. MTO is a synthetic anthraquinone drug with anti-tumor, immunomodulatory, and anti-inflammatory effects. Currently, MTO has been used to treat acute non lymphocytic leukemia, hormone resistant prostate cancer, ovarian cancer, gastric cancer, and liver cancer. MTO micelles can enhance the chemotherapy effect of MTO and provide a synergistic effect of photothermal therapy, which may also have therapeutic effects on other types of cancer.

Third, it can be used for the treatment of Multiple sclerosis. Multiple sclerosis is an autoimmune neurodegenerative disease, which can lead to dysfunction of the central nervous system. Previously, MTO has been used to treat secondary progressive Multiple sclerosis, because it can inhibit the activation and proliferation of T cells and B cells, and reduce the damage of nerve fiber sheath. MTO micelles are expected to provide a safer and more effective treatment for Multiple sclerosis, because it can reduce the toxicity of MTO to the heart and enhance the neuroprotective effect through Photothermal effect.

Next, they will continue to optimize the preparation and characterization methods of MTO micelles, improve their stability, drug loading, and photothermal conversion efficiency, and reduce the toxicity and side effects of MTO micelles.

It will also explore the molecular details of MTO micelles' mild photothermal chemotherapy synergistic mechanism, reveal the mechanism of MTO micelles' influence on the signal pathway, gene expression and protein level of triple negative breast cancer cells, and explore how to regulate the expression and function of HSP70 in the end.

At the same time, the scope of application of the mild photothermal chemotherapy synergistic effect of MTO micelles will also be expanded, and the therapeutic effect of MTO micelles on other types of cancer cells and tumor models will be tested, as well as their safety against normal cells and tissues.

In addition, the research group will also promote the clinical transformation of MTO micelles, and evaluate the therapeutic effect and safety of MTO micelles on human triple negative breast cancer patients through more preclinical and clinical trials, so as to provide better treatment options for triple negative breast cancer patients.

References

1. Chen, Z., Li, S., Li, F., Qin, C., Li, X., Qing, G.,...& Xiao, Y (2023). DNADAmageInducerMitoxantroneAmplifiesSynergisticMid - PhotothermalChemotherapyforTNBCvia DecreasingHeatShockProtein70ExpressionAdvancedScience2206707

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