Abstract
Bones are the most frequent site for breast cancer cells to settle and spread (metastasise); bone metastasis is considered to have a substantial impact on the quality of patients with common cancers. However, majority of breast cancers develop insensitivity to conventional chemotherapy which provides only palliation and can induce systemic side effects. In this study we evaluated the effect of free Dox and CaCO3/Dox nanocrystal on MCF-7 breast cancer using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide), neural red, and lactate dehydrogenase colorimetric assays while DNA fragmentation and BrdU genotoxicity were also examined. Apoptogenic protein Bax, cytochrome C, and caspase-3 protein were analysed. Morphological changes of MCF-7 were determined using contrast light microscope and scanning and transmission electron microscope (SEM and TEM). The findings of the analysis revealed higher toxicity of CaCO3/Dox nanocrystal and effective cells killing compared to free Dox, morphological changes such as formation of apoptotic bodies, membrane blebbing, and absent of microvilli as indicated by the SEM analysis while TEM revealed the presence of chromatin condensation, chromosomal DNA fragmentation, cell shrinkage, and nuclear fragmentation. Results of TUNEL assay verified that most of the cells undergoes apoptosis by internucleosomal fragmentation of genomic DNA whereas the extent of apoptotic cells was calculated using the apoptotic index (AI). Therefore, the biobased calcium carbonate nanocrystals such as Dox carriers may serve as an alternative to conventional delivery system.
Highlights
Bone is one of the most common sites of metastasis in individuals with breast cancer
We examined the effect of drug loading and cytotoxicity of doxorubicin delivery for targeting metastatic bone cancer using biobase calcium carbonate nanocrystal
We further provided morphological evidence to prove the cellular apoptotic pathway, using higher resolution equipment such as transmission electron microscope (TEM) and Scanning Electron Microscope (SEM) which were believed to be the gold standard method of apoptotic analysis, as this instrument can differentiate between various cellular deaths pathways through morphological changes
Summary
Bone is one of the most common sites of metastasis in individuals with breast cancer. The major drawback of chemotherapy is the lack of selectivity to cancer cells and an absence of specificity, thereby causing the development of multidrug resistance during prolonged treatment and less accumulation of the drug at its intracellular target site of action. This is due to the overexpression of efflux transporters such as P-glycoprotein (P-gp), which is the major mechanism of drug resistance in cancer [4, 5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
