Biocompatible PCL-nanofibers scaffold with immobilized fibronectin and laminin for neuronal tissue regeneration.

Recent advances in regenerative medicine have given hope in overcoming and rehabilitating complex medical conditions. In this regard, the biopolymer poly-ε-caprolactone (PCL) may be a promising candidate for tissue regeneration, despite lacking the essential bioactivity. The present study used PCL nanofibers (NFs) scaffold decorated with the extracellular matrix proteins fibronectin and laminin combined for neuronal regeneration. The potential for the dual proteins to support neuronal cells and promote axonal growth was investigated. Two NFs scaffolds were produced with PLC concentrations of 12% or 15%. Under scanning electron microscopy, both scaffolds evidenced uniform diameter distribution in the range of 358 nm and 887 nm, respectively, with >80% porosity. The Brunauer-Emmett-Teller (BET) test confirmed that the fabricated NFs mats had a high surface area, especially for the 12% NFs with 652 m2/g compared to 254 m2/g for the 15% NFs. The proteins of interest were successfully conjugated to the 12% PCL scaffold through chemical carbodiimide reaction as confirmed by Fourier-transform infrared spectroscopy. The addition of fibronectin and laminin together was shown to be the most favorable for cellular attachment and elongation of neuroblastoma SH-SY5Y cells compared to other formulations. Light microscopy revealed longer neurite outgrowth, higher cellular projected area, and lower shape index for the cells cultured on the combined proteins conjugated fibers, indicating enhanced cellular spread on the scaffold. This preliminary study suggests that PCL nanoscaffolding conjugated with matrix proteins can support neuronal cell viability and neurite growth.

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand.

Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.

Dual-Targeted Lactoferrin Shell-Oily Core Nanocapsules for Synergistic Targeted/Herbal Therapy of Hepatocellular Carcinoma.

Herein, both strategies of synergistic drug combination together with dual active tumor targeting were combined for effective therapy of hepatocellular carcinoma (HCC). Therefore, based on the tumor sensitizing action, the herbal quercetin (QRC) was co-delivered with the targeted therapeutic drug sorafenib (SFB), preformulated as phospholipid complex, via protein shell-oily core nanocapsules (NCs). Inspired by the targeting action of lactoferrin (LF) via binding to LF receptors overexpressed by HCC cells, LF shell was electrostatically deposited onto the drug-loaded oily core to elaborate LF shell-oily core NCs. For dual tumor targeting, lactobionic acid (LA) or glycyrrhetinic acid (GA) was individually coupled to LF shell for binding to asialoglycoprotein and GA receptors on liver cancer cells, respectively. Compared to LF and GA/LF NCs, the dual-targeted LA/LF-NCs showed higher internalization into HepG2 cells with 2-fold reduction in half-maximal inhibitory concentration compared to free combination therapy after 48 h. Moreover, dual-targeted LF-NCs showed powerful in vivo antitumor efficacy. It was revealed as significant downregulation of the mRNA expression levels of nuclear factor-kappa B and tumor necrosis factor α as well as suppression of Ki-67 protein expression level in diethylnitrosamine (DEN)-induced HCC mice (P < 0.05). Furthermore, dual-targeted LF-NCs attenuated the liver toxicity induced by DEN in animal models. Overall, this study proposes dual-targeted LF-NCs for combined delivery of SFB and QRC as a potential therapeutic HCC strategy.