Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier

Multidrug resistance proteins （MDRPs）, which are implicated in the mediation of multidrug resistance in tumors, represent the main obstacle to successful chemotherapy. As curcurnin （Cur） exerts inhibitory effects on both the expression and function of MDRPs, a nanocarrier for the co-delivery of Cur and doxorubicin （DOX） was prepared to overcome MDR tumors through their synergistic effects. Owing to the overexpression of legumain in tumors, the release profile of DOX from this nanocarrier was designed to be legumain modulated, which was achieved by bridging DOX to a basic material （chitosan） with a legumain- sensitive peptide. Compared with nanoparticles that only contain DOX, the coadministration of DOX and Cur significantly inhibited multidrug resistance （P 〈 0.05） in a multidrug-resistant cancer cell model （MCF-7/ADR cell line）, with cytotoxicity to normal cells （L929 cell line）. Such inhibition could be ascribed to the increased DOX accumulation in the MCF-7/ADR nucleus. The co-delivery system exhibited good anticancer effects through prolonged circulation time, improved tumor-targeting efficiency, elevation of the tumor inhibition activity, and the suppression of MDRP expression. These data revealed the enormous potential of this co-delivery system for cancer therapy, especially in the later stages where multidrug resistance may develop.

Enzymatic formation of curcumin in vitro and in vivo

The recent classification of curcumin （Cur） as a pan-assay interference compound （PAINS） and an invalid metabolic panaceas （IMPS） candidate demonstrated the controversial nature of Cur as a drug lead owing to its aggregation in aqueous phase and inherent instability in vivo. Here, we report a simple prodrug approach to generate nanoparticles of Cur in situ that allow it to function reproducibly as an anticancer and an anti-inflammatory agent. Diphosphorylated curcumin （Cur-2p）, a precursor of Cur and a substrate of alkaline phosphatase （ALP）, exhibited drastically improved chemical stability and low aggregation in water. After conversion to curcumin around or inside cancer cells by ALP, Cur-2p selectively inhibited cancer cells that overexpressed ALP, but did not affect normal cells. Moreover, the intravitreal injection of Cur-2p resulted in excellent intraocular biocompatibility with no apparent damage to the morphology and visual function of retina, as shown by fundus imaging, optical coherence tomography （OCT）, and histological observation. A rodent model of uveitis showed that Cur-2p significantly suppressed the inflammation response compared with Cur. As a rational approach to investigate and apply PAINS and IMPS candidates, this work presents a straightforward method to maximize the potential of drug leads and ultimately fulfil the promises and potential clinical benefits of PAINS and IMPS candidates.

Self-assembled small molecular weight hydrogels of prodrugs

Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding,DNA encoding and etc.Inspired by this inherent biological process,nanostructure such as nanofibers,nanosphere,and so on formed by the therapeutic agents and its derivatives that can further self-assemble into supramolecular hydrogels have attained considerable attentions in the field of drug delivery due to its favorable features such as high and precise drug payload,carrier-free and excellent biocompatibility.Additionally,the prodrug hydrogelator can be rationally designed to fine-tune over its drug release behavior and degradation in response to various biological stimulus（temperature,p H,ionic strength and etc.）.This review summarized and discussed the recent advancement in the self-assembled small molecular weight hydrogels of prodrugs.

Bimorph deformable mirror based adaptive optics scanning laser ophthalmoscope for retina imaging in vivo

A bimorph deformable mirror （DM） with a large stroke of more than 30 μm using 35 actuators is presented and characterized for an adaptive optics （AO） confocal scanning laser ophthalmoscope application. Facilitated with a Shack-Hartmann wavefront sensor, the bimorph DM-based AO operates closed-loop AO corrections for hu- man eyes and reduces wavefront aberrations in most eyes to below 0.1 μm rms. Results from living eyes, including one exhibiting ~5D of myopia and ~2D of astigmatism along with notable high-order aberrations, reveal a prac- tical efficient aberration correction and demonstrate a great benefit for retina imaging, including improving resolution, increasing brightness, and enhancing the contrast of images.