In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy

In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.

A single Au nanoparticle anchored inside the porous shell of periodic mesoporous organosilica hollow spheres

理想的金属催化剂对沥滤或粒子凝块与反应试剂，很多暴露的活跃地点，和高稳定性要求容易的接触。抛锚尽管几乎没报导，在多孔的壳内的一个金属核心可以由于常规支持的金属安排的集成把这些优点合为 core@void@shell 体系结构。然而，完成这由于弱 coreshell 亲密关系是极其困难的。此处，第一次，我们报导一条途径由增加核心壳相互作用克服这挑战。在这方面，我们综合了一个单个 Au 核心是的新奇 Au@void@periodic mesoporous organosilica (PMO ) 在体系结构坚定地在空 PMO 范围的多孔的壳内抛锚了。在之间的非共有原子价相互作用(vinylpyrrolidone )(PVP ) poly，一些 functionalized Au 和 PMO 的乙烷一半向多孔的壳便于 Au 核心的运动在期间 Au@SiO2@PMO 的选择碱的蚀刻。抛锚壳的 Au 核心以与活跃地点的试剂和暴露的接触比在常规 Au@void@PMO 的推迟的核心优异，并且因此为 4-nitrophenol 减小显示出更高催化的效率。这里表明的方法论提供新卓见因为有核心的万用的多功能的 nanostructures 的制造在空壳内抛锚了。

Improvement of Stability and Anticancer Activity of ChlorambuciI-Tetrapeptide Conjugate Vesicles

Chlorambucil is a classic nitrogen mustard drug that has been used in the treatment of cancers. It may induce neutropenia, thrombocytopenia and other side effects because of its short lifetime and off-target effect. In this report, chlorambucil-tetrapeptide （AAAK, A3K） conjugate vesicles were developed to improve the stability and bioactivity of chlorambucil. First of all, chlorambucil-A3K conjugate was synthesized by solid phase synthesis strategy. Sec- ondly, the chlorambucil-A3K conjugate was assembled and characterized by critical aggregation concentration, cir- cular dichroism, dynamic light scattering and transmission electron microscopy. The results indicated that the chlo- rambucil-A3K conjugate can be assembled to form spherical vesicles with an average diameter of 390.5 nm, and high drug loading about 47.1% is reached. Surprisingly, the preliminary biological evaluation of the chlorambu- cil-A3K conjugate vesicles revealed the best in vitro anticancer activity against HeLa, HepG-2 and MCF-7 cell lines compared with chlorambucil and chlorambucil-A3K conjugate free drugs. Furthermore, conjugate vesicles showed excellent in vivo antitumoral activity. It can be partly attributed to their vesicular structure which isolates chloram- bucil active moiety from aqueous solution to retard degradation before killing cancer cells. Therefore, chlorambu- cil-peptide （A3K） conjugate vesicles may be an alternative delivery system of chlorambucil.