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.