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Published on: January 15, 2015
Cetyltrimethylammonium chloride-loaded mesoporous silica nanoparticles as a mitochondrion-targeting agent for tumor
Menghuan Tang1, Peng Zhang2, Jiahui Liu1
1Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China zhenghz@swu.edu.cn.
Abstract:
Mitochondria play an important role in supplying cellular energy, cell signaling and governing cell death. In addition, mitochondria have also been proved to be essential for tumor generation and development. Thus, mitochondrion-targeting therapeutics and treatments have emerged as promising strategies against cancer. However, the lack of mitochondrion-targeting agents has limited their application. To this end, we report cetyltrimethylammonium chloride-loaded mesoporous silica nanoparticles conjugated with human serum albumin (CTAC@MSNs-HSA) as a mitochondrion-targeting agent for anticancer treatment. As the structure-directing agent in the synthesis of MSNs, CTAC is stored within MSNs. Due to their desirable size and HSA receptor-mediated transcytosis, CTAC@MSNs-HSA show great cellular uptake and enhanced accumulation in the cytoplasm. Positively charged CTAC could actively target mitochondria by interacting with the negatively charged mitochondria membrane, and then lead to the dysfunction of mitochondria by decreasing mitochondrial potential and intracellular ATP levels, resulting in the necrosis and apoptosis of MCF-7 cells. Therefore, significant antitumor activity is observed by in vitro studies. Moreover, in vivo studies confirm that the CTAC@MSNs-HSA are able to induce cancer cell death and efficiently inhibit tumor growth. These results demonstrate the potential of CTAC@MSNs-HSA in cancer therapeutics as well as providing insights into mitochondrion-targeting treatment.
Insights
Cetyltrimethylammonium chloride-loaded mesoporous silica nanoparticles conjugated with human serum albumin (CTAC@MSNs-HSA) effectively target mitochondria. This leads to cancer cell death and tumor growth inhibition, showing promise for anticancer therapeutics.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Biology
Background:
- Mitochondria are crucial for cellular energy, signaling, and death, and are implicated in cancer development.
- Targeting mitochondria presents a promising strategy for cancer treatment.
- A lack of effective mitochondrion-targeting agents currently limits this approach.
Purpose of the Study:
- To develop and evaluate cetyltrimethylammonium chloride-loaded mesoporous silica nanoparticles conjugated with human serum albumin (CTAC@MSNs-HSA) as a novel mitochondrion-targeting agent for anticancer therapy.
Main Methods:
- Synthesis of CTAC@MSNs-HSA nanoparticles.
- Evaluation of cellular uptake and cytoplasmic accumulation.
- Assessment of mitochondrial targeting via interaction with the mitochondrial membrane.
- Analysis of mitochondrial dysfunction, including potential and ATP levels.
- Investigation of MCF-7 cell apoptosis and necrosis.
- In vitro and in vivo antitumor activity studies.
Main Results:
- CTAC@MSNs-HSA exhibited significant cellular uptake and cytoplasmic accumulation.
- The nanoparticles actively targeted mitochondria, leading to decreased mitochondrial potential and ATP levels.
- Induction of MCF-7 cell necrosis and apoptosis was observed.
- Significant in vitro antitumor activity was demonstrated.
- In vivo studies confirmed efficient tumor growth inhibition and cancer cell death induction.
Conclusions:
- CTAC@MSNs-HSA nanoparticles show significant potential as mitochondrion-targeting anticancer therapeutics.
- The study provides insights into the development of novel strategies for mitochondrion-targeted cancer treatment.
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