Biomaterials and cells for cardiac tissue engineering: Current choices.

The major purpose of cardiac tissue engineering is to engineer cells on scaffolds and use it as a substitute to infarcted cardiac cells. With an ever-increasing risk of cardiac diseases there is an increasing need to have a stable and sustainable approach to cure such ailments. This review provides a comprehensive update on the cell sources and biomaterials essential for cardiac tissue engineering, ensuring their biocompatibility under a variety of conditions. Cells can be obtained from allogenic or autologous sources. The cells sources described in this paper are cardiomyocytes, a variety of stem cells, fibroblasts and parthenogenetic cells. Scaffolds to seed the cells should fulfill various criteria, the most important ones being non-immunogenicity, biodegradability and native tissue mimicking. There are several kinds of scaffolds including hydrogels, prefabricated matrices, decellularized scaffolds and cell sheets. Using this knowledge of cell sources and scaffold fabrication, production of various tissue engineered products is possible.

Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy.

The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intratumoral concentration, and an insulin resistance "class effect." This study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-α-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polythylene glycol)]. The supramolecular nanoparticles (SNP) that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the SNPs exerted a temporally sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer treatment.