Intracellular trafficking and cellular uptake mechanism of mPEG-PLGA-PLL and mPEG-PLGA-PLL-Gal nanoparticles for targeted delivery to hepatomas

Liu, Peifeng; Sun, Yongli; Wang, Qi; Sun, Ying; Li, He; Duan, Yourong

doi:10.1016/j.biomaterials.2013.10.020

Cited by 94 publications

(79 citation statements)

References 36 publications

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“…20 Indeed, hepatoma, the most common type of human cancer, is known to express abnormally high level of the asialoglycoprotein receptors (ASGP-Rs) that are responsive to carbohydrate motifs including the N-acetyl galactosamine, galactose, and lactose. 4,6,10,[21][22][23][24][25] It is also noteworthy that malignant tumor cells also elicit changes in the stroma for rapid growth and progression, thus creating an abnormal microenvironment characterized by hypoxia, acidity, and overexpression of surface receptors and enzymes. 1,4,9 Given the distinct tumor microenvironment, designing polymeric micelles that are responsive to redox reaction, pH, and temperature changes to facilitate tumor-specific drug release has been an effective tumor-targeted drug delivery approach.…”

Section: Lou Et Almentioning

confidence: 99%

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

Lou¹,

Zhang²,

Zhang³

et al. 2017

IJN

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A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC 50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy.

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Section: Lou Et Almentioning

confidence: 99%

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

Lou¹,

Zhang²,

Zhang³

et al. 2017

IJN

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Section: Hca: Detailed Mechanisms Of Np Internalization and Intracellmentioning

confidence: 75%

“…Although, genistein (an established inhibitor of caveolin-mediated uptake) reduced the uptake of these particles, the kinetics of internalization and the lack of colocalization with caveolin suggested that multiple machineries effect uptake of this particle type. A more recent study across a wider range of cell types further endorsed this thesis for PEG-based particles [88].Surface charge on particles is another key determinant for the uptake mechanism used. Using 100-nm polystyrene NP, spinning disk microscopy and quantitative image analysis were used in mesenchymal stem cells to show that carboxylated-functionalized polystyrene NPs were internalized fivefold more efficiently than nonfunctionalized anionic NPs [89].…”

mentioning

confidence: 79%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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“…7,8 Preparation of l-MBPc scaffolds l-MBPC scaffolds with Li-MBG content of 35 wt% were prepared by solvent casting and particulate leaching method. The mPEG-PLGA-b-PLL was added into the solvent (chloroform), followed by continuous stirring to disperse uniformly.…”

Section: Preparation Of Mpeg-plga-b-pll Block Copolymermentioning

confidence: 99%

“…[1][2][3][4] Recently, an amphiphilic block copolymer of monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (mPEG-PLGA-b-PLL) was synthesized, 5,6 and the studies indicated that mPEG-PLGA-b-PLL with good biocompatibility and degradability would be a promising and effective carrier for the delivery of drugs and genes. 7,8 In the past few years, the applications of mesoporous bioglasses (MBGs) for bone tissue regeneration have been proposed, because their large surface area and high pore volume may enhance their bioactivity and promote new bone formation. 9,10 The large surface area and high pore volume of MBG result in higher surface chemical reactivity compared with normal bioglasses (BGs) without mesopores.…”

Section: Introductionmentioning

confidence: 99%

Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium-containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer

Cai¹,

Guo²,

Shen³

et al. 2015

IJN

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Biocomposite scaffolds of lithium (Li)-containing mesoporous bioglass and monomethoxy poly(ethylene glycol)-poly(D,L-lactide- co -glycolide)-poly(L-lysine) (mPEG-PLGA- b -PLL) copolymer were fabricated in this study. The results showed that the water absorption and degradability of Li-containing mesoporous bioglass/mPEG-PLGA- b -PLL composite (l-MBPC) scaffolds were obviously higher than Li-containing bioglass/mPEG-PLGA -b -PLL composite (l-BPC) scaffolds. Moreover, the apatite-formation ability of l-MBPC scaffolds was markedly enhanced as compared with l-BPC scaffolds, indicating that l-MBPC scaffolds containing mesoporous bioglass exhibited good bioactivity. The cell experimental results showed that cell attachment, proliferation, and alkaline phosphatase activity of MC3T3-E1 cells on l-MBPC scaffolds were remarkably improved as compared to l-BPC scaffolds. In animal experiments, the histological elevation results revealed that l-MBPC scaffolds significantly promoted new bone formation, indicating good osteogenesis. l-MBPC scaffolds with improved properties would be an excellent candidate for bone tissue repair.

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Intracellular trafficking and cellular uptake mechanism of mPEG-PLGA-PLL and mPEG-PLGA-PLL-Gal nanoparticles for targeted delivery to hepatomas

Cited by 94 publications

References 36 publications

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

High-content analysis for drug delivery and nanoparticle applications

Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium-containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer

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