A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.     

Dendrimer as nanocarrier for drug delivery

Dendrimers are novel three dimensional, hyperbranched globular nanopolymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery and cavities in the interior distinguish them amongst the available polymers. Applications of dendrimers in a large variety of fields have been explored. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Terminal functionalities provide a platform for conjugation of the drug and targeting moieties. In addition, these peripheral functional groups can be employed to tailor-make the properties of dendrimers, enhancing their versatility. The present review highlights the contribution of dendrimers in the field of nanotechnology with intent to aid the researchers in exploring dendrimers in the field of drug delivery.     

Prevalence and antimicrobial resistance of Salmonella isolated from an integrated broiler chicken supply chain in Qingdao,China

The present study analyzed the prevalence and antimicrobial resistance of Salmonella along an integrated broiler chicken supply chain. A total of 172 Salmonella isolates were recovered from 1148 samples collected from four sample sources (breeder farms, broiler farms, abattoir, and retail markets), representing nine production stages. These Salmonella isolates were examined for antimicrobial susceptibility to 12 different antimicrobial agents using a disk diffusion assay. Among them, 168 were identified as six different serotypes of Salmonella enterica. The predominant serotype was S. Enteritidis (n = 116), followed by S. Infantis (n = 18), S. Gueuletapee (n = 16), S. Derby (n = 12), S. Meleagridis (n = 4), and S. London (n = 2). The remaining four isolates were serogroup-untypeable. A majority of the 172 isolates (96.51%) was resistant to one or more antibiotics and 61.05% of the Salmonella isolates showed a multidrug resistance phenotype. Statistical analysis indicated the one risk product stage for Salmonella contamination occurred in the sample source at the abattoir, specifically the stage of Carcasses after chilling. The majority of S. Enteritidis isolates shared the same pulsed-field gel electrophoresis (PFGE) cluster, suggesting that the S. Enteritidis strain might spread along the broiler chicken supply chain. The prevalence and antimicrobial resistance of Salmonella in different production stages suggest the importance of controlling Salmonella in the broiler chicken supply chain for public health, underlying the need for improved measures of reducing carcass contamination in abattoirs and the appropriate use of antimicrobials in broiler flocks.     

姜黄素通过调控组蛋白乙酰化修饰上调乳腺癌MCF-7和MCF-7/DOX细胞中MDR1表达

目的:从组蛋白乙酰化修饰角度探讨姜黄素上调乳腺癌MCF-7和MCF-7/DOX细胞中多药耐药基因1（multidrug resistance protein 1,MDR1）表达水平的作用机制。方法: CCK-8（Cell Counting Kit-8）法观察姜黄素对MCF-7和MCF-7/DOX细胞生长增殖以及多柔比星敏感性的影响;Real time PCR和Western blot方法检测姜黄素处理前后两种细胞中MDR1 mRNA和蛋白质表达水平的变化;染色质免疫共沉淀技术（chromatin immunoprecipitation assay,CHIP）检测姜黄素对两种细胞中MDR1启动子区相关组蛋白H3、H4乙酰化水平的影响。结果: 不同浓度姜黄素处理72 h对MCF-7和MCF-7/DOX细胞的生长增殖有显著抑制作用,其IC50值分别为22.03 μmol/L和27.46 μmol/L;10 μmol/L姜黄素处理72 h可显著提高两种细胞多柔比星敏感性,多柔比星IC50值分别下降了57.14%和54.52%（P<0.05）;姜黄素处理MCF-7和MCF-7/DOX细胞后,MDR1在mRNA水平分别上调(32.90±0.96）和（5.70±0.55）倍（P<0.05）,在蛋白质水平分别上调（2.26±0.18）与（2.90±0.21）倍（P<0.05）;CHIP结果显示姜黄素对两种细胞中MDR1启动子区相关组蛋白H3、H4的乙酰化水平均有显著上调作用。结论:姜黄素在增强MCF-7和MCF-7/DOX细胞多柔比星敏感性的同时,可通过调控MDR1启动子区相关组蛋白H3、H4的乙酰化水平而上调MDR1的表达。     

Construction of functional aliphatic polycarbonates for biomedical applications

Aliphatic polycarbonates are one important kind of biodegradable polymers and have been commonly used as integral components of engineered tissues, medical devices and drug delivery systems. As far as the biomedical application is concerned, traditional aliphatic polycarbonates usually suffer from the strong hydrophobicity, deficient functionality, and insufficient compatibility with cell/organs. Consequently, the application is quite limited in scope. Due to the imparted appealing properties, aliphatic polycarbonates bearing specifically designed functional/reactive groups attract great interest from researchers in the recent years. The present review outlines the development up to date concerning the design and biomedical application of functional aliphatic polycarbonates, with an emphasis on their ring-opening (co)polymerization preparation.     

Synthesis and functionalization of nanoengineered materials using click chemistry

The synthesis of nanoengineered materials with precise control over material composition, architecture and functionality is integral to advances in diverse fields, including biomedicine. Over the last 10 years, click chemistry has emerged as a prominent and versatile approach to engineer materials with specific properties. Herein, we highlight the application of click chemistry for the synthesis of nanoengineered materials, ranging from ultrathin films to delivery systems such as polymersomes, dendrimers and capsules. In addition, we discuss the use of click chemistry for functionalizing such materials, focusing on modifications aimed at biomedical applications.     

Co‐delivery of methotrexate and doxorubicin via nanocarriers of star‐like poly(DMAEMA‐block‐HEMA‐block‐AAc) terpolymers

Combined therapy is a promising strategy for clinical cancer treatment with synergistic effects. The purpose of the work reported was to evaluate a smart nanocarrier for co‐delivery of doxorubicin (DOX) and methotrexate (MTX). Since star‐like nanocarriers can load a high dose of drugs with various properties, we developed star polymer nanomicelles based on poly[(2,2‐dimethylaminoethyl methacrylate)‐block‐(2‐hydroxyethyl methacrylate)‐block‐(acrylic acid)] having potential for multi‐drug delivery. The nanomicelles demonstrated high encapsulation efficiency, i.e. 97.1% for DOX and 79.5% for MTX. To this end, the star‐like terpolymers were synthesized via atom transfer radical polymerization with pentaerythritol as an initiator. The micellar properties and dual stimuli‐responsive behaviour of the terpolymers were investigated using transmission electron microscopy, field emission scanning electron microscopy and dynamic light scattering measurements, concluding that this co‐therapy offers a promising approach for cancer treatment. © 2019 Society of Chemical Industry     

MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2

Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2.     

A tumor-targeting nano doxorubicin delivery system built from amphiphilic polyrotaxane-based block copolymers

Amphiphilic polyrotaxane (PR)-based block copolymers are synthesized by end-capping polypseudorotaxanes (PPRs) formed from distal 2-bromopropionyl terminated Pluronic F68 and a varying amount of β-cyclodextrins (β-CDs) using hydrophilic polymeric blocks of poly(ethylene glycol) methyl ether methacrylate (PEGMA) yielded via the in situ ATRP. To gain a tumor-targeting nano doxorubicin (DOX) delivery system for cancer chemotherapy, an active tumor-targeting ligand, folic acid (FA), is conjugated to the two ends of the resulting copolymers through “azide-ethylene click chemistry”. The conjugated copolymers enable to self-assemble into unique core–shell structured micelles in aqueous solution and to load DOX into the hydrophobic core. The drug loading content is increased from 2.0 wt% to 25.5 wt% with respect to the blank block copolymer most likely due to the hydrogen bond interaction between DOX and β-CDs threaded. After drug loading, the size of the micelles is enlarged from 120 nm to 220 nm in diameter as determined by dynamic light scattering (DLS) analysis. Moreover, these tumor-targeted polymeric micelles exhibit a slower and sustained DOX release behavior. The cell uptake and distribution, as well as the cytotoxicity of the polymeric micelles are also evaluated toward the MDA-MB-231 cells. The FA-conjugated PR-based block copolymer micelles appear to be internalized by the cancer cells via FA receptor mediated endocytosis; thus, they present enhanced cytotoxicity to the selected breast cancer cells.     

Biodegradable synthetic polymers: Preparation, functionalization and biomedical application

Biodegradable polymers have been widely used and have greatly promoted the development of biomedical fields because of their biocompatibility and biodegradability. The development of biotechnology and medical technology has set higher requirements for biomedical materials. Novel biodegradable polymers with specific properties are in great demand. Biodegradable polymers can be classified as natural or synthetic polymers according to the source. Synthetic biodegradable polymers have found more versatile and diverse biomedical applications owing to their tailorable designs or modifications. This review presents a comprehensive introduction to various types of synthetic biodegradable polymers with reactive groups and bioactive groups, and further describes their structure, preparation procedures and properties. The focus is on advances in the past decade in functionalization and responsive strategies of biodegradable polymers and their biomedical applications. The possible future developments of the materials are also discussed.