No abstract

Growth factors, first known for their essential role in the initiation of mitosis, are required for a variety of cellular processes and their localized delivery is considered as a rational approach in their therapeutic application to assure a safe and effective treatment while avoiding unwanted adverse effects. Noncovalent immobilization of growth factors as well as their covalent conjugation is amongst the most common strategies for localized delivery of growth factors. Today, immobilized and covalently conjugated growth factors are considered as a promising drug design and are widely used for protein reformulation and material design to cover the unwanted characteristics of growth factors as well as improving their functions. Selection of a suitable conjugation technique depends on the substrate chemistry and the availability of functional reactive groups in the structure of growth factor, the position of reactive groups in growth factor molecules and its relation with the receptor binding area, and the intention of creating either patterned or unpatterned conjugation. Various approaches for growth factor reformulation have been reported. This review provides an overview on chemical conjugation of growth factors and covers the relevant studies accomplished for bioconjugation of growth factors and their related application.

BackgroundPoly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues.MethodsPLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.ResultsSize, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg).ConclusionIn conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.

Oxidative stress associated cell damage is one of the key factors in neurodegeneration development and is highly related to the presence of transition metal ions including iron. Herein, deferasirox, a high affinity iron chelator, was conjugated to lactoferrin molecules by carbodiimide mediated coupling reaction to create a novel drug delivery system with higher brain permeability through receptor mediated transcytosis. Each lactoferrin molecule was averagely attached to 4 to 6 deferasirox molecules resulting in water-soluble conjugated nanostructures which were purified and characterized. Neuroprotective effects of lactoferrin conjugated nanostructures and their cellular uptake were evaluated in differentiated PC12 cell line, and the molecular mechanisms involved in such neuroprotection were elucidated. Lactoferrin conjugates were able to interfere in apoptotic caspase cascade by affecting the expression level of caspase-3, PARP, Bax and Bcl-2. Furthermore, an elevation in the expression level of autophagy markers including Atg7, Atg12-Atg5 and LC3-II/LC3-I ratio was observed. Intraperitoneal injection of lactoferrin conjugates was able to significantly attenuate learning deficits induced by beta amyloid injection in a rat model of Alzheimer's disease, which further confirms a potential neuroprotective effect for lactoferrin conjugated deferasirox in neurodegenerative disorder management through metal chelation therapy.

In this review, Kamalinia et al. discuss mRNA display and its role in peptide and protein design.