Hydrogen-Bonded Tannic Acid-Based Anticancer Nanoparticle for Enhancement of Oral Chemotherapy.

Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Currently, nanoparticulate drug delivery systems (NDDS) exhibit many unique advantages in mediating oral drug delivery; however, many anticancer drugs that were susceptible in hostile gastrointestinal (GI) environment showed poor permeability across intestinal epithelium, and most materials used as drug carriers are nonactive excipients and displayed no therapeutically relevant function, which leads to low oral bioavailability and therapeutic efficacy of anticancer drugs (e.g., paclitaxel). Inspired by these, in this study, paclitaxel (PTX) was used as a model drug, depending on intermolecular hydrogen-bonded interactions, PTX-loaded tannic acid/poly( N-vinylpyrrolidone) nanoparticles (PTX-NP) were produced by a flash nanoprecipitation (FNP) process. The optimized PTX-NP showed an average diameter of 54 nm with a drug encapsulation efficiency of 80% and loading capacity of 14.5%. Molecular dynamics simulations were carried out to illuminate the assembling mechanism of hydrogen-bonded PTX-NP. In vitro and in vivo results confirmed that PTX-NP showed pH-dependent intestinal site-specific drug release, P-gp inhibitory function by tannic acid (TA), prolonged intestinal retention, and improved trans-epithelial transport properties. Oral administration of PTX-NP generated a high oral delivery efficiency and relative oral bioavailability of 25.6% in rats, and further displayed a significant tumor-inhibition effect in a xenograft breast tumor model. These findings confirmed that our PTX-NP might be a promising oral drug formulation for chemotherapy.

Supramolecular Nanoparticles of Insulin and Pentapeptide for Inhibition of Fibrillation and Controlled Release.

Despite their obvious advantages of making insulin injections less frequent and reducing discomfort for diabetic patients, various controlled release formulations of insulin still have some problems caused by the fibrillation of protein. Here, we demonstrate that pentapeptide FVPRK inspired from the C-terminal of the insulin receptor α-CT can form supramolecularassembled nanoparticles with insulin, showing a controlled release of insulin and an inhibition effect of insulin fibrillation. These nanoparticles were proved non-toxic through cytotoxicity study and the assembling mechanisms was explored by computer simulations, indicating that the strong π-π interaction between C-terminus of insulin B-chain and Phe of the pentapeptide may provide the corresponding driving force. These results suggest that supramolecular nanoparticles composed of insulin and pentapeptide have the potential to improve insulin therapy.

Synthesis, crystal structure, cytotoxicity and action mechanism of a Rh(iii) complex with 8-hydroxy-2-methylquinoline as a ligand.

A rhodium(iii) complex, [Rh(MQ)(DMSO)2Cl2] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC50 values in the micromolar range (6.52-17.86 µM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca2+ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway.