Extracellular and intracellular barriers in non-viral gene delivery

Ruponen, Marika; Honkakoski, Paavo; Rönkkö, Seppo; Pelkonen, Jukka; Tammi, Markku; Urtti, Arto

doi:10.1016/j.jconrel.2003.08.004

“…Lipid reagents such as 1,2- (22). Given their high density of positive charges, these lipids are generally mixed with adjuvant lipids such as cholesterol to reduce the energy required to separate the ionically linked DNA and cationic lipids.…”

Section: Nanoparticle Platforms: Emerging Translational Nanodrug Delimentioning

confidence: 99%

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

Babu

¹

,

Templeton

²

,

Munshi

³

et al. 2014

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Abstract. Nanotechnology has enabled the development of novel therapeutic and diagnostic strategies, such as advances in targeted drug delivery systems, versatile molecular imaging modalities, stimulus responsive components for fabrication, and potential theranostic agents in cancer therapy. Nanoparticle modifications such as conjugation with polyethylene glycol have been used to increase the duration of nanoparticles in blood circulation and reduce renal clearance rates. Such modifications to nanoparticle fabrication are the initial steps toward clinical translation of nanoparticles. Additionally, the development of targeted drug delivery systems has substantially contributed to the therapeutic efficacy of anti-cancer drugs and cancer gene therapies compared with nontargeted conventional delivery systems. Although multifunctional nanoparticles offer numerous advantages, their complex nature imparts challenges in reproducibility and concerns of toxicity. A thorough understanding of the biological behavior of nanoparticle systems is strongly warranted prior to testing such systems in a clinical setting. Translation of novel nanodrug delivery systems from the bench to the bedside will require a collective approach. The present review focuses on recent research efforts citing relevant examples of advanced nanodrug delivery and imaging systems developed for cancer therapy. Additionally, this review highlights the newest technologies such as microfluidics and biomimetics that can aid in the development and speedy translation of nanodrug delivery systems to the clinic.

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“…Uptake by oral ingestion is ideal for patient comfort and, while still largely speculative for dendrimers [97], there is now evidence that uptake occurs in the rat gut [98]; this route is enticing based on an increasing recognition that nanoparticle uptake across the gut is largely governed by the physicochemical properties and surface chemistries of oral drug delivery vehicles [99]. Typically, to get to the target site in the body, the drug candidate must avoid becoming trapped with the extracellular matrix, which has been shown to hinder cellular uptake and reduce the efficiency of other nanosized delivery vehicles [100]; instead entry into the bloodstream is generally required for transit to the intended site of action.…”

Section: 54mentioning

confidence: 99%

Dendrimers in Cancer Treatment and Diagnosis

Sampathkumar

¹

,

Yarema

²

2003

Nanotechnologies for the Life Sciences

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The sections in this article are Overview Introduction Basic Properties and Applications of Dendrimers Structural Features and Chemical and Biological Properties Basic Features of Dendritic Macromolecules are Inspired by Nature Comparison of the Properties of Dendrimers and Conventional Synthetic Polymers Comparison of the Properties of Dendrimers and Proteins (a Biological Polymer) Dendritic Macromolecules Possess a Wealth of Possible Applications Methods for Dendrimer Synthesis History and Basic Strategies Cascade Reactions are the Foundation of Dendrimer Synthesis Dendrimer Synthesis has Expanded Dramatically in the Past Two Decades Strategies, Cores, and Building Blocks for Dendritic Macromolecules Dendrimers are Constructed from Simple “Building Blocks” The Synthesis of Dendrimers Follows Either a Divergent or Convergent Approach Heterogeneously‐functionalized Dendrimers Basic Description and Synthetic Considerations Glycosylation is an Example of Surface Modification with Multiple Bioactivities Dendrimers in Drug Delivery Dendrimers are Versatile Nano‐devices for the Delivery of Diverse Classes of Drugs Dendritic Drug Delivery: Encapsulation of Guest Molecules Dendrimers have Internal Cavities that can Host Encapsulated Guest Molecules Using Dendrimers for Gene Delivery Release of Encapsulated “Pro‐drugs” Covalent Conjugation Strategies Dendrimers Overcome many Limitations Inherent in Polymeric Conjugation Strategies Dendrimer Conjugates can be Used as Vaccines Release of Covalently‐delivered “Pro‐drugs” Fine‐tuning Dendrimer Properties to Facilitate Delivery and Ensure Bioactivity Delivery Requires Avoiding Non‐specific Uptake “Local” Considerations: Contact with, and Uptake by, the Target Cell Drug Delivery: Ensuring the Biocompatibility of Dendritic Delivery Vehicles Biocompatibility Entails Avoiding “Side Effects” such as Toxicity and Immunogenicity Water Solubility and Immunogenicity Inherent and Induced Toxicity Dendrimers in Cancer Diagnosis and Treatment Dendrimers have Attractive Properties for Cancer Treatment Dendrimer‐sized Particles Passively Accumulate at the Sites of Tumors Multifunctional Dendrimers can Selectively Target Biomarkers found on Cancer Cells Methods for Targeting Specific Biomarkers of Cancer Targeting by Folate, a Small Molecule Ligand Targeting by Monoclonal Antibodies Dendrimers in Cancer Diagnosis and Imaging Labeled Dendrimers are Important Research Tools for Biodistribution Studies Towards Clinical Use: MRI Imaging Agents Steps Towards the Clinical Realization of Dendrimer‐based Cancer Therapies The Stage is now set for Dendrimer‐based Cancer Therapy Boron Neutron Capture Therapy Innovations Promise to Speed Progress “Mix‐and‐Match” Strategy of Bifunctional Dendritic Clusters Towards Therapeutic Exploitation of Glycosylation Abnormalities found in Cancer Towards Targeting Metabolically‐engineered Carbohydrate Epitopes Concluding Remarks Acknowledgments

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“…The transfection method used to express the protein of interest should have minimal effect on the cells to allow unbiased measurements. However, transfection protocols pose a number of strains onto cells in order to deliver foreign DNA to the nucleus and to escape the cells natural defense mechanisms against incorporation of non-self DNA [1]. Polyethylenimine (PEI) is a synthetic polymer agent for nucleic acid delivery in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

An adapted protocol to overcome endosomal damage caused by polyethylenimine (PEI) mediated transfections.

Jonker

¹

,

Heus

²

,

Faber

³

et al. 2017

Matters

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Transfection of cells using polyethylenimine (PEI) polymers is a widely used technique for gene insertion and exogenous protein expression that offers several advantages over virus or lipid-based transfection methods. PEI facilitates endocytosis of DNA into the cell, release of DNA from the endolysosomal system and protection from nucleases. Although PEI is extensively investigated for application in research and therapy, the mechanism of its release from the endosomal system has remained a point of debate. The most prevailing model states that PEI causes endosomal rupture, resulting in release of PEI-DNA complexes into the cytosol. Hence, the use of PEI transfection should be applied with great care in studies on the endosomal system. Here we study the effect of PEI transfections on the endolysosomal system. Using fluorescent and electron microscopy we find a decrease in early endosomes after PEI transfection. Adapting the PEI transfection protocol by including a chase time after initial uptake of the PEI-DNA polyplexes rescues this phenotype without affecting transfection efficiency. Our data result in an adapted protocol for PEI transfection that can be used in studies involving the endolysosomal system.

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Extracellular and intracellular barriers in non-viral gene delivery

Cited by 138 publications

References 13 publications

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

Dendrimers in Cancer Treatment and Diagnosis

An adapted protocol to overcome endosomal damage caused by polyethylenimine (PEI) mediated transfections.

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