Systems biology approach in the formulation of chemically defined media for recombinant protein overproduction.

The cell culture medium is an intricate mixture of components which has a tremendous effect on cell growth and recombinant protein production. Regular cell culture medium includes various components, and the decision about which component should be included in the formulation and its optimum amount is an underlying issue in biotechnology industries. Applying conventional techniques to design an optimal medium for the production of a recombinant protein requires meticulous and immense research. Moreover, since the medium formulation for the production of one protein could not be the best choice for another protein, hence, the most suitable media should be determined for each recombinant cell line. Accordingly, medium formulation becomes a laborious, time-consuming, and costly process in biomanufacturing of recombinant protein, and finding alternative strategies for medium development seems to be crucial. In silico modeling is an attractive concept to be adapted for medium formulation due to its high potential to supersede laboratory examinations. By emerging the high-throughput datasets, scientists can disclose the knowledge about the effect of medium components on cell growth and metabolism, and via applying this information through systems biology approach, medium formulation optimization could be accomplished in silico with no need of significant amount of experimentation. This review demonstrates some of the applications of systems biology as a powerful tool for medium development and illustrates the effect of medium optimization with system-level analysis on the production of recombinant proteins in different host cells.

Aptamer functionalized curcumin-loaded human serum albumin (HSA) nanoparticles for targeted delivery to HER-2 positive breast cancer cells.

In this study, an HER2 aptamer-decorated curcumin-loaded human serum albumin nanoparticle (Apt-HSA/CCM NP) was developed and characterized as a new anticancer formulation for targeted delivery to human epithelial growth factor receptor 2 (HER2) overexpressing breast cancer cells. Conjugation of HER2 Apt to the surface of HSA NPs was confirmed by gel electrophoresis and FTIR analysis. The obtained NPs have the hydrodynamic diameter of 281.1 ±â€¯11.1 nm and zeta potential of -33.3 ±â€¯2.5 mV. The data demonstrated that encapsulation of curcumin in HSA NPs by desolvation method has increased water solubility by 400 folds. Fluorescent microscopy image demonstrated remarkable cytoplasmic uptake of Apt-HSA/CCM NPs in HER2-overexpressing SK-BR-3 cells compared to unconjugated counterparts. Cytotoxicity experiments demonstrated no significant difference between cytotoxic effect of free curcumin and non-targeted HSA/CCM NPs in both HER2 positive and HER2 negative cell lines. However, the toxicity of Apt-HSA/CCM NPs was significantly higher and cell viability reached 36% after 72 h in SK-BR3 cell line. These results suggest that this targeted delivery system has the potential to be considered as a promising candidate for the treatment of HER2 positive cancer cells.

Redox responsive curcumin-loaded human serum albumin nanoparticles: Preparation, characterization and in vitro evaluation.

The purpose of this study was to fabricate redox-responsive human serum albumin (HSA) nanoparticles (NPs) through self-assembly of HSA molecules for incorporation of curcumin (CCM) as a hydrophobic drug molecule. The structural changes of HSA in self-assembly process of nanoparticle formation were investigated using fluorescence, UV-vis, circular dichroism spectroscopy and X-ray diffraction. Spectroscopy data show changes in secondary and tertiary structures of HSA in the process of nanoparticle formation, which can be indicative of the interaction of the hydrophobic drug with HSA molecules. Unlike free CCM, nanoparticulate curcumin is readily dispersed in aqueous medium. Furthermore, self-assembled HSA-CCM NPs release CCM in an environment imitating the intracellular environment with the trigger of acidic pH and redox potential. The in vitro release studies showed that at pH7.4 only 26% CCM was released from CCM-loaded HSA NPs in 48h. However, the release of CCM was significantly accelerated in the presence of 10mM glutathione (GSH) at pH7.4 or pH5.5, in which 57% and 70% of CCM was released, respectively. The incorporation of CCM in HSA nanoparticles enhanced the cellular uptake of CCM in comparison with free CCM results in higher anticancer efficacy against MCF-7 cells.

Ligand-modified Biopolymeric Nanoparticles as Efficient Tools for Targeted Cancer Therapy.

Non-specific distribution of chemotherapeutic agents in the body where they affect both cancer as well as normal cells resulting in serious side effects is the major reason for the high mortality rate of cancer. Thus, there is a need for developing targeted delivery strategies specially employing nanoplatform-based cancer therapies that provide specific targeting to tumor cells. In this regard, biopolymeric nanoplatforms such as liposomes, protein- and polysaccharide- based nanoparticles have gained more attention due to their biocompatibility, biodegradability and less toxicity. In terms of targeting, monoclonal antibodies (mAbs), folic acid (FA) and transferrin (Tf) can be considered as the moieties to be attached to the nanoplatforms to deliver their payload to its site of action. This review article focuses on the recent progress in the field of targeted drug and gene delivery systems with emphasizes on liposomes, protein (specially human and bovine serum albumin)-based nanoparticles and polysaccharide (specially chitosan and dextran)-based nanoparticles as the biopolymeric nanoplatforms, which are decorated with mAbs, FA and Tf as the targeting ligands.