Inhalable iron redox cycling powered nanoreactor for amplified ferroptosis-apoptosis synergetic therapy of lung cancer

Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination strategy.However,the low intracellular Fenton level and accumulation of therapeutics at the lesion site greatly limit the efficacy of ferroptosis therapy.To overcome these two bottlenecks,an inhalable metal polyphenol network(MPN)-hybrid liposome,encoded as LDG,was proposed for enhancing the intracellular Fenton reaction level by co-delivering the ferroptosis inducer dihydroartemisinin(DHA)and the ferrous ion(Fe2+)donor MPN.The synthesized LDG had excellent nebulization performance which significantly improved the accumulation in the lungs,about 8.2 times of intravenous injection.In terms of anticancer mechanisms,MPN raised the intracellular level of Fe2+by constructing iron cycling in the weakly acidic environment of tumors.Triggered by Fe2+,DHA with peroxide-bridge structure underwent a high level of Fenton-like reaction,promoted the production of intracellular reactive oxygen species(ROS)and induced strong ferroptosis while cooperating with apoptosis.LDG exhibited extraordinary antitumor ability in an orthotopic lung tumor model,whose tumor inhibition efficiency was 1.53(P=0.0014)and 1.32(P=0.0183)times of the LG group(liposomes coated with gallic acid(GA)-Fe MPN)and LD group(liposomes loaded with DHA),respectively,showing the strongest anticancer effect.In conclusion,the constructed MPN-hybrid liposomes could be a potent custom nanoplatform for pulmonary delivery and underscored the great potential of ferroptosis-apoptosis synergetic therapy.

Plasma protein corona forming upon fullerene nanocomplex:Impact on both counterparts

Protein corona refers to the structure composed of biomolecules adsorbed on the surface of nanomaterials.The study on the effect of the interaction between protein and nanoparticles can provide an important guide for the application of nanodrug delivery.To provide a reference for the research on fullerene(C60)nanocomplex drug delivery systems,this work studied the interaction between C60 nanocomplex and a variety of plasma proteins.Research showed that the protein binding with C60 nanocomplex did not change the charge properties of protein.The proteins induced the aggregation of C60 nanocomplex.The circular dichroism spectra showed that the secondary structure of the proteins changed after binding to C60 nanocomplex.The ultraviolet-visible spectra showed that the effect of C60 nanocomplex on proteins was concentration-dependent.The fluorescence spectra showed that C60 nanocomplex could intrinsic fluorescence alteration of proteins.The adsorption capacity of C60 nanocomplex to proteins was changed at 0 h and 4 h.The interaction between nanocomplex and proteins might affect the morphological characteristics of nanocomplex and the conformation of proteins.This work could provide a reference for the research and development of C60 nanocomplex and other carbon-based nanocomplex as nanoparticulate drug delivery systems.

情境感知的移动经验取样方法及工具研究

移动互联网+教育促进了教育数据采集方法的革新。移动经验取样法是一种移动技术与经验取样方法相结合的纵向即时数据采集方法。本研究在系统梳理移动经验取样法的理论基础、取样方法和相关工具的基础上,重点对情境感知移动经验取样工具的功能流程和关键技术进行重点分析,设计并实现了一款指向真实学习情境的教育即时数据采集工具。该工具以智能终端为信息采集载体,实现随机取样、间隔取样、基于事件的取样和设备取样四种取样方式。接着,从感知有用性与感知易用性两个方面,通过焦点小组讨论对工具进行了评价与完善,并对工具的功能进行了横向比较。最后,对工具的应用进行了展望,以期为移动经验取样工具的本土化研究及应用提供借鉴与参考。

The effect of organic ligand modification on protein corona formation of nanoscale metal organic frameworks

Nanoscale metal organic frameworks(NMOFs)have been widely reported in biomedical field for their unique porous structure and tunable multifunctionality.However,when administrated in vivo,the protein corona will be formed on the surface of NMOFs,significantly affecting their biodistribution,pharmacokinetics and drug release.Few studies paid attention to the protein corona formation process and its influencing factors of NMOFs.As a well-established strategy for altering structure features of NMOFs,the organic ligand modification may have effect on the protein corona formation process,which is to be investigated.In this study,the zirconium(Zr)-based UIO66 was chosen as model NMOFs,the organic ligand of which was modified with amino group(-NH_(2))or carboxyl group(-COOH)to synthesize UIO66-NH_(2)and UIO66-2COOH,respectively.Bovine serum albumin(BSA)was chosen as model protein to investigate the protein corona formation process of NMOFs.The current results showed that the-COOH modification remarkably enhanced the BSA adsorption on NMOFs while-NH_(2)slightly decreased the protein binding affinity.These differences may be ascribed to the two different dominate protein corona formation modes,i.e.,surface coating mode and porous embedded mode.The protein corona formation did not affect the crystal phase of NMOFs but increased the content ofα-helix of BSA.Ultimately,upon protein corona formation,the cellular uptake of NMOFs was significantly affected.We believe our study will provide a new research paradigm to the design and applications of NMOFs.

Bibliometric landscape of the researches on protein corona of nanoparticles

Unclear biological fate hampers the clinical translation of nanoparticles for biomedical uses.In recent years,it is documented that the formation of protein corona upon nanoparticles is a critical factor leading to the ambiguous biological fate.Efforts have been made to explore the protein corona forming behaviors on nanoparticles,and rearrangement of the relevant studies will help to understand the current trend of such a topic.In this work,the publications about protein corona of nanoparticles in Science Citation Index Expanded database of Web of Science from 2007 to 2020(1417 in total)were analyzed in detail,and the bibliometrics landscape of them was showcased.The basic bibliometrics characteristics were summarized to provide an overall understanding.Citation analysis was performed to scrutinize the peer interests of these papers.The research hotspots in the field were evaluated,based on which some feasible topics for future studies were proposed.In general,the results demonstrated that protein corona of nanoparticles was a prospective research area,and had attracted global research interests.It was believed that this work could comprehensively highlight the bibliometrics landscape,inspire further exploitation on protein corona of nanoparticles,and ultimately promote the clinical translation of nanoparticles.