Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the“masking”effect caused by high-abundance proteins.The relative abundance of middleand low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 highabundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins identified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab

Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.Methods:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR)effect.This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system.The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.Results:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native cetuximab.Nano(cetuximab)accumulated in tumor tissues via the EPR effect and released cetuximab.The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 weeks.Conclusions:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the EPR effect,which facilitated further tumor accumulation of the tAbs.This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.

Preparation and characterization of enzyme-responsive zwitterionic nanoparticles for monoclonal antibody delivery

Monoclonal antibodies have been used in many diseases,but how to improve their delivery efficiency is still a key issue.As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies,in this study,zwitterionic monomers,sulfobetaine methacrylate(SBMA),and 3-[[2-(methacryloyloxy)ethyl]dimethylammonio]propionate(CBMA)were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions.The results from dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FTIR)and transmission electron microscopy(TEM)indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent.These nanoparticles were spherical with the sizes of(18.7±1.9)nm(SBMA nanoparticle)and(18.2±2.1)nm(CBMA nanoparticle),and the surface contained zwitterionic polymers.It was revealed that they had no cytotoxicity,could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells,and was able to effectively penetrate endothelial cells(>2%)by transwell.Therefore,the development of this strategy has a great prospect for the delivery of monoclonal antibodies.

Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins

Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.

Surface photodynamic ion sterilization of ITO-Cu_(2)O/ZnO preventing touch infection

Pathogenic microbial infections are threatening the people’s health and even life.The most common channel of infections can be caused by skin contact,especially hand touching facilities such as touching screen.In this work,Cu_(2)O covered with ZnO nanofilm was prepared on the surface of indium tin oxide conductive glass by electrodeposition and the followed atomic layer deposition process.This composite coating had a light transmittance of 71.5%,which met the light transmission needs of touch screen device.Electron spin resonance spectra showed that composite materials can generate more reactive oxygen species(ROS)than a single component under solar light irradiation.This was because a p-n junction with a built-in electric field was formed at the interface after Cu_(2)O contacting with ZnO.In the process of photocatalysis,photogenerated electrons and holes migrated at the interface driven by the built-in electric field,which promoted the separation of carriers.The antibacterial rate against Staphylococcus aureus reached 92.5%after 3 min of light irradiation with simulated sunlight due to the synergy of ROS and Cu ions,Zn ions.Therefore,this work may provide a potential method for antibacterial application of preventing hand touch infections.

Systemic delivery of microRNA for treatment of brain ischemia

Brain ischemia is the second leading cause of death and the third leading cause of disability in the world.Systemic delivery of microRNA,a class of molecules that regulate the expression of cellular proteins associated with angiogenesis,cell growth,proliferation and differentiation,holds great promise for the treatment of brain ischemia.However,their therapeutic efficacy has been hampered by poor delivery efficiency of microRNA.We report herein a platform technology based on microRNA nanocapsules,which enables their effective delivery to the disease sites in the brain.Exemplified by microRNA-21,intravenous injection of the nanocapsules into a rat model of cerebral ischemia could effectively ameliorate the infarct volume,neurological deficit and histopathological severity.

Functionalization of PEG-PM PC-based polymers for potential theranostic applications

The synergistic effect of polyethylene glycol(PEG)and poly(2-methacry-loyloxyethyl phosphorytcholine)(PMPC)can effectively reduce the protein absorption,which is beneficial to theranostics.However,PEG-PMPC-based polymers have rarely been used as nanocarriers in the theranostic field due to their limited modifiability and weak interaction with other materials.Herein,a plain method was proposed to endow them with the probable ability of loading small active agents,and the relationship between the structure and the ability of loading hydrophobic agents was explored,thus expanding their applications.Firstly,mPEG-PMPC or 4-arm-PEG-PMPC polymer was synthesized by atom transfer radical polymerization(ATRP)using mPEG-Br or 4-arm-PEG-Br as the macroinitiator.Then a strong hydrophobic segment,poly(butyl methacrylate)(PBMA),was introduced and the ability to load small hydrophobic agents was further explored.The results showed that linear mPEG-PMPC-PBMA could form micelles 50-80 nm in size and load the hydrophobic agent such as Nile red efficiently.In contrast,star-like 4-arm-PEG-PMPC-PBiyiA,a monomolecular micelle(10-20 nm),could hardly load any hydrophobic agent.This work highlights effective strategies for engineering PEG-PMPC-based polymers and may facilitate the further application in numerous fields.

Erratum to:Functionalization of PEG–PMPC-based polymers for potential theranostic applications

In the original version of this article, the first affiliation “Tianjin Key Laboratory of Composite and Functional Materials,Tianjin 300350, China” should be “Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University,Tianjin 300350, China”.