Facile Separation of PEGylated Liposomes Enabled by Anti-PEG scFv.

PEGylated nanocarriers have gained increasing attention due to reduced toxicity and enhanced circulation compared with free drugs. According to guidances of drug regulatory departments worldwide, it is crucial to determine free and liposomal drug concentrations; however, the conventional used separation methods including dialysis, ultrafiltration, and solid-phase extraction (SPE) have drawbacks of time-consuming, drug leakage, environmental pollution or error bias of trace level drug. Here we developed a facile PEG-scFv-based separation method combined with HPLC to quantify free doxorubicin (DOX) and liposomal DOX in plasma. Anti-PEG single chain variable fragment antibody (PEG-scFv) was adopted to sediment PEGylated liposomes by simple incubation and low speed centrifugation. Compared to SPE, it demonstrated sufficient accuracy and sensitivity to evaluate free and liposomal DOX with intact liposomes. Therefore, it can serve as an alternative approach of SPE, which is suitable for quality assessment and pharmacokinetics evaluation of PEGylated liposomal drugs and possible other PEGylated nanocarriers.

Deciphering Protein Corona by scFv-Based Affinity Chromatography.

It remains challenging to precisely decipher the structural and functional characteristics of protein coronas. To overcome the drawbacks frequently occurring in the traditional separation methods, an anti-PEG single-chain variable fragment (PEG-scFv) based affinity chromatography (AfC) was developed to achieve precise and efficient separation of protein coronas on PEGylated liposomes (sLip). His-tagged PEG-scFv could readily capture sLip without affecting protein corona compositions, and separate sLip/protein complex from plasma protein aggregates and endogenous vesicles through the Ni-NTA column. AfC demonstrated 43-fold higher protein corona collecting efficiency than centrifugation, which was extremely crucial for separation of in vivo protein coronas due to the limitation of sample size. AfC evaded contamination by endogenous vesicles and protein aggregates occurring in centrifugation, and reserved the loosely bound proteins, providing an unprecedented approach to deeply decipher protein coronas. The scFv-based AfC also paves new avenues for the separation of protein coronas formed on other nanomedicines.

Preparation of hollow-fiber nanofiltration membranes of high performance for effective removal of PFOA and high resistance to BSA fouling.

Nanofiltration (NF) process has become one of the most promising technologies to remove micro-organic combined water pollution. Developing a NF membrane material with efficient separation for perfluorooctanoic acid (PFOA) combined pollution is highly desired, this manuscript targets this unmet need specifically. In this work, hydrophilic SiO2 nanoparticles with various contents blended with carboxylic multiwalled carbon nanotube were used to modify poly (m-phenylene isophthal amide) (SiO2/CMWCNT/PMIA) hollow fiber NF membrane. The modified membrane with 0.1 wt% SiO2 doping exhibits way better fouling resistance with irreversible fouling ratio decreased dramatically from 18.7% to 2.3%, and the recovery rate of water flux increases significantly from 81.2% to 97.7%. The separation experiment results had confirmed that the modified membrane could improve the rejection from 97.2% to 98.6% for perfluorooctanoic acid (PFOA) and its combined pollution with bovine serum albumin (BSA). It is clear that this reported SiO2/CMWCNT/PMIA hollow fiber NF membrane potentially could be applied in water treatment. This research also provides a theoretical basis for efficiently removal of PFOA and its combined pollution by NF membrane.

Insight into the influence of humic acid and sodium alginate fractions on membrane fouling in coagulation-ultrafiltration combined system.

Membrane fouling has become the one of main obstacles for the widespread application of membrane technology in water treatment processes. Coagulation as pretreatment is proven to be effective for the alleviation of membrane fouling. In this study, the influence of humic acid (HA)/sodium alginate (SA) fractions in the structure and resistance of cake layer on the membrane surface was investigated. The presence of SA at an appropriate fraction could facilitate the formation of large and loosely branched flocs and thereby form a more permeable cake layer on the membrane surface due to good bridging and charge neutralization abilities of SA molecules. The particle image velocimetry (PIV) technique was employed for monitoring the dynamic formation process of cake layer under different HA/SA fractions. The cake layer with a higher thickness was observed to be rapidly formed on the membrane surface at the presence of SA in water. According to the theoretical analysis, the membrane fouling in coagulation-ultrafiltration (UF) combined system demonstrated to be highly dependent on the size and intra-porosity of flocs. The fractal dimension of flocs might have an impact on the resistance of cake layer through affecting the porosity of aggregated flocs. The SA molecules could be used as the coagulant aid for effective alleviation of membrane fouling and the improvement of filtration performance in a coagulation-UF combined system.

Lipid droplet-hitchhiking probe creates Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques.

Since atherosclerosis, a disease characterized by abnormal arterial lipid deposition, may lead to fatal cardiovascular diseases, imaging of atherosclerotic plaques is of great value for their pathological assessment. In this study, we propose a lipid droplet (LD)-hitchhiking strategy to in situ create Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques via homologous targeting effect. In our design, functional liposomes (DCP liposomes) composed of phospholipid dioleoylphosphatidylserine (DOPS), a novel LD inducer we found, and Cypate-PC, a synthesized lipid-like molecular probe, have demonstrated great capability of inducing LDs in monocytes/macrophages while being enveloped into the resulting Trojan foam cells. Taking advantage of homologous targeting effect, the imaging probe hitchhikes on the LDs in Trojan foam cells for targeted transport to the plaque sites. Moreover, the confinement in highly hydrophobic LDs endows the imaging probe with high efficiency in light absorption, enabling greatly intensified fluorescence/photoacoustic signals. The DCP liposomes have shown great potency in inducing the generation of Trojan foam cells, and eventually ex vivo fluorescence imaging and in vivo photoacoustic imaging of atherosclerotic plaques. The proposed strategy provides more insights into the design of targeted imaging methodologies, and also an effective avenue to facilitate the evaluation and subsequent treatment of atherosclerotic plaques.

Interplay between nanomedicine and protein corona.

Nanomedicine is recognized as a promising agent for diverse biomedical applications; however, its safety and efficiency in clinical practice remains to be enhanced. A priority issue is the protein corona (PC), which imparts unique biological identities to prototype and determines the actual biological functions in biological fluids. Decades of work has already illuminated abundant considerations that influence the composition of the protein corona. Thereinto, the physical assets of nanomedicines (e.g., size and shape, surface properties, nanomaterials) and the biological environment collectively play fundamental roles in shaping the PC, including the types and quantities of plasma proteins. The properties of nanomedicines are dependent on certain factors. This review aims to explore the applications of nanomedicines by regulating their interplay with PC.

Anti-PEG scFv corona ameliorates accelerated blood clearance phenomenon of PEGylated nanomedicines.

Anti-PEG antibodies have been witnessed in patients and experimental animals, accelerating the blood clearance (termed ABC phenomenon) of PEGylated nanomedicines by activating complement after absorption on the nano-surface. The ABC phenomenon presents an obstacle to the clinical translation of PEGylated nanomedicines. Herein, an anti-PEG single-chain variable fragment (PEG-scFv) that possesses a low molecule weight (30 kDa) and high PEG binding affinity was exploited to ameliorate the ABC phenomenon of PEGylated liposomes (sLip). Pre-deposition of PEG-scFv on the surface of sLip was incompetent to activate complement due to the lack of Fc chains, exhibiting negligible influence on in vivo performance of sLip in naïve rats (without anti-PEG antibodies). However, PEG-scFv effectively competed the binding of anti-PEG IgM in rats that were pre-stimulated with low dose of sLip, thus ameliorated the ABC phenomenon of sLip. PEG- scFv was also effective to inhibit the binding of anti-PEG antibodies with sLip in human plasma and the consequent complement activation, presenting a promising tool to improve the performance of PEGylated nanomedicines and to mitigate individual difference occurred by the varying levels of anti-PEG antibodies in the clinic. The application of anti-PEG scFv paves a new avenue for the development of nanocarriers to achieve precise medication.

[A Meta-analysis of the effect of non-surgical periodontal therapy on inflammatory factors in patients with chronic kidney disease and periodontitis].

OBJECTIVE: A study was conducted to systematically evaluate the clinical efficacy of inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. METHODS: We searched the databases of CNKI, Wanfang, CBM, PubMed, Embase, and Cochrane Library from inception to December 2019. Two reviewers independently collected all literature related to inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. These factors include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature was screened according to the inclusion and exclusion criteria. The quality of the studies was strictly evaluated, and the data were extracted. The literature of randomized controlled trials in accordance with the standards was Meta-analyzed with Revman 5.3 software. RESULTS: Six randomized controlled trials were included. Compared with the control groups, the results of meta-analysis showed that non-surgical periodontal therapy significantly reduced the levels of CRP [MD=-0.58, 95%CI (-1.13, -0.02), P=0.04] and IL-6 [MD=-2.76, 95%CI (-5.15, -0.37), P=0.02] in these patients but not that of TNF-α [MD=-3.87, 95%CI (-8.79, 1.05), P=0.12]. CONCLUSIONS: Simultaneous regular renal treatment and non-surgical periodontal therapy can help relieve the periodontal damage on patients with chronic kidney disease and periodontitis. Moreover, it can improve the status of some inflammatory factors. This finding is conducive to the control and treatment of chronic kidney disease and periodontitis and needs to be a focus of research and in clinical operation.