Efficiency of novel nanocombinations of bovine milk proteins (lactoperoxidase and lactoferrin) for combating different human cancer cell lines

Abstract

Bovine lactoperoxidase (LPO) and lactoferrin (LF) are suitable proteins to be loaded or adsorbed to chitosan nanoparticles (NPs) for preparing stable nanoformulations with potent anticancer activity. In the present study, nanocombinations of LPO and LF revealed improvement in their stability and activity compared to single (free or nanoformulated) bovine proteins. The coating or loading of LPO-loaded NPs with LF resulted in the highest synergistic cytotoxicity effect against Caco-2, HepG-2, MCF-7 and PC-3 cells in comparison with other NPs and free proteins without causing toxicity toward normal cells. This synergistic improvement in the anticancer activity was apoptosis-dependent that was confirmed by severe alterations in cellular morphology, high percentage of annexin-stained cells and sub-G1 populations as well as nuclear staining with orange fluorescence of treated cancer cells. Additionally, significant alterations in the expression of well characterized cellular proliferation and apoptosis guards (NF-κB, Bcl-2 and p53) in these NPs-treated cancer cells compared to 5-fluorouracil (5-FU) treated cells. Our findings provide for the first time that these new synergistic nanoformulated forms of LPO and LF were superior in their selective apoptosis-mediating anticancer effect than free form of these proteins and 5-FU. LF coating or loading of LPO-loaded NPs present as promising therapy for cancer.

In vitro assessment of the bioactivities of sericin protein extracted from a bacterial silk-like biopolymer

“…The half maximal inhibitory concentration (IC 50 ) values of BNES that cause 50% cell viability were calculated by Graphpad Instate soware and the selectivity index (SI), known as the IC 50 ratio on normal cells versus tumour cells, was calculated as discussed previously. 32 2.6.3. Morphological changes.…”

Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres

“…Also, the use of Lf as a coating agent due to its accumulation in breast tissue can be effective in targeting breast cancer 22 . In several studies, the anti-cancer activity of Lf is associated with the capacity of apoptosis through down-regulation of Bcl-2 mRNA 23 , along with up-regulation of the pro-apoptotic Bax and Caspase 3 mRNA 24 . Besides, Lf can result in targeted delivery of NP containing Doxo to tumor site 25 as well as an increase in the blood circulation time due to ability to escape from mononuclear phagocyte system (MPS) 26 and controlling drug release 2 , whereas, the anti-cancer mechanism of Lf ' is not fully understood.…”

Evaluation of the selective toxic effect of the charge switchable diethyldithiocarbamate-loaded nanoparticles between hepatic normal and cancerous cells

“…Using nanoparticles (NPs) in cancer therapy is anticipated to overcome the existing obstacles of anticancer drugs by increasing their stability, sustaining their release and decreasing their toxicity against healthy tissues. Due to the controlled size of NPs, it allows anticancer drugs to be delivered selectively to cancer cells and interact with intracellular biomolecules causing targeting of cancer death with low toxic effects on normal cells 22 – 24 . On the other hand, physiological conditions (hyperpermeability and acidic microenvironment) of cancer cells provide many benefits to NPs to effectively target them 25 , 26 .…”

“…On the other hand, physiological conditions (hyperpermeability and acidic microenvironment) of cancer cells provide many benefits to NPs to effectively target them 25 , 26 . NPs that are based on the cationic polysaccharides chitosan have been promising due to their biodegradability, biocompatibility and non-antigenicity 24 . Its positive charge enhances intracellular uptake of the loaded drugs due to its affinity to negatively charged cell membrane of either normal or cancer cells.…”