Cross-Linked Microparticles as Carriers for the Delivery of Plasmid DNA for Vaccine Development

Goh, Sarah L.; Murthy, Niren; Xu, Mingcheng; Fréchet, Jean M. J.

doi:10.1021/bc034159n

Cited by 104 publications

(98 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The significant difference in antisense effects between Lac-PEG-ODN/PLL PIC micelle and Lac-PEG-Mal-ODN/PLL PIC micelle can be ascribed to the difference in the natures of their linkages between PEG and ODN segments. The Lac-PEG-ODN conjugate contains an acid-labile (bthiopropionate) linkage that is cleavable in the low-pH endosome environment, provoking the release of hundreds of free PEG strands from the PIC micelle to increase the colloidal osmotic pressure within the endosomal compartment, [18] and eventually to induce the swelling and disruption of the endosome. This event may facilitate the transport of free antisense ODN into cytoplasm.…”

Section: Cellular Association and Internalization Of The Pic Micellesmentioning

confidence: 99%

Smart Polyion Complex Micelles for Targeted Intracellular Delivery of PEGylated Antisense Oligonucleotides Containing Acid‐Labile Linkages

et al. 2005

View full text Add to dashboard Cite

A novel pH-sensitive and targetable antisense ODN delivery system based on multimolecular assembly into polyion complex (PIC) micelles of poly(L-lysine) (PLL) and a lactosylated poly(ethylene glycol)-antisense ODN conjugate (Lac-PEG-ODN) containing an acid-labile linkage (beta-propionate) between the PEG and ODN segments has been developed. The PIC micelles thus prepared had clustered lactose moieties on their peripheries and achieved a significant antisense effect against luciferase gene expression in HuH-7 cells (hepatoma cells), far more efficiently than that produced by the nonmicelle systems (ODN and Lac-PEG-ODN) alone, as well as by the lactose-free PIC micelle. In line with this pronounced antisense effect, the lactosylated PIC micelles showed better uptake than the lactose-free PIC micelles into HuH-7 cells; this suggested the involvement of an asialoglycoprotein (ASGP) receptor-mediated endocytosis process. Furthermore, a significant decrease in the antisense effect (27 % inhibition) was observed for a lactosylated PIC micelle without an acid-labile linkage (thiomaleimide linkage); this suggested the release of the active (free) antisense ODN molecules into the cellular interior in response to the pH decrease in the endosomal compartment is a key process in the antisense effect. Use of branched poly(ethylenimine) (B-PEI) instead of the PLL for PIC micellization led to a substantial decrease in the antisense effect, probably due to the buffer effect of the B-PEI in the endosome compartment, preventing the cleavage of the acid-labile linkage in the conjugate. The approach reported here is expected to be useful for the construction of smart intracellular delivery systems for antisense ODNs with therapeutic value.

show abstract

Section: Cellular Association and Internalization Of The Pic Micellesmentioning

confidence: 99%

Smart Polyion Complex Micelles for Targeted Intracellular Delivery of PEGylated Antisense Oligonucleotides Containing Acid‐Labile Linkages

et al. 2005

View full text Add to dashboard Cite

show abstract

“…175 In addition, the versatility towards the encapsulation of different biologically active macromolecules such as e.g. plasmid DNA 176 clearly demonstrates the great potential of these delivery systems. Especially the divinyl functionalization of the used crosslinkers enables their utilization in radical copolymerizations with a broad variety of monomers thus giving rise to the facile preparation of a multitude of acid-degradable polymeric microgels.…”

Section: Microgels Containing Hydrolytically Cleavable Crosslinkersmentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

View full text Add to dashboard Cite

This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

show abstract

“…So wurde zum Beispiel beobachtet, dass Plasmid-DNS in säurelabilen vernetzten Nanogelen die Sekretion von Zytokin-IL-6 und die Immunstimulation von Makrophagen auslösen kann. [18] In einer anderen Arbeit wurden Nanogele mit Ovalbumin als Modellantigen beladen. Nach Inkubation mit dendritischen Zellen aus dem Knochenmark wurde eine verstärkte Prä-sentation von Ovalbuminfragmenten beobachtet.…”

Section: Angewandte Chemieunclassified

“…Dieser Prozess resultiert in der Zersetzung des Nanogels und der Freisetzung der Fracht. [18,19] Die Gruppe um Matyjaszewski nutzte die radikalische Atomtransferpolymerisation (ATRP) für die Synthese von stabilen vernetzten Nanogelen aus wasserlöslichen Polymeren. [20] Mithilfe eines disulfidhaltigen Vernetzers konnten biologisch abbaubare Nanogele aufgebaut werden.…”

Section: Introductionunclassified

Nanogele als pharmazeutische Trägersysteme: winzige Netzwerke mit großen Möglichkeiten

Kabanov

Vinogradov

2009

Angewandte Chemie

View full text Add to dashboard Cite

Als Nanogele bezeichnet man gequollene Netzwerke aus hydrophilen oder amphiphilen Polymeren in der Größenordnung von einigen Dutzend bis Hundert Nanometern. Sie wurden als Trägersysteme für den Transport von Wirkstoffen entwickelt. Durch gezieltes Design können biologisch aktive Moleküle spontan eingebunden werden, sei es mithilfe von Salzbrücken, Wasserstoffbrücken oder hydrophoben Wechselwirkungen. Polyelektrolyt‐Nanogele sind in der Lage, gegensätzlich geladene niedermolekulare Wirkstoffe und Biomakromoleküle wie Oligo‐ und Polynucleotide (siRNA, DNS) sowie Proteine aufzunehmen. Die Gastmoleküle wechselwirken elektrostatisch mit den ionischen Polymerketten des Gels und werden dadurch in den winzigen Nanogelen gebunden. Zahlreiche chemische Funktionalitäten stehen zur Verfügung, um Gruppen für Bildgebungsverfahren und den gezielten Wirkstofftransport im Nanogel einzuführen. Letzteres kann z. B. durch abbaubare oder schaltbare Vernetzungen erreicht werden. Aktuelle Arbeiten zeichnen eine aussichtsreiche Zukunft für biomedizinische Anwendungen von Nanogelen.

show abstract

Cross-Linked Microparticles as Carriers for the Delivery of Plasmid DNA for Vaccine Development

Cited by 104 publications

References 49 publications

Smart Polyion Complex Micelles for Targeted Intracellular Delivery of PEGylated Antisense Oligonucleotides Containing Acid‐Labile Linkages

Smart Polyion Complex Micelles for Targeted Intracellular Delivery of PEGylated Antisense Oligonucleotides Containing Acid‐Labile Linkages

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Nanogele als pharmazeutische Trägersysteme: winzige Netzwerke mit großen Möglichkeiten

Contact Info

Product

Resources

About