Combining reactive triblock copolymers with functional cross-linkers: A versatile pathway to disulfide stabilized-polyplex libraries and their application as pDNA vaccines

Journal of Controlled Release : Official Journal of the Controlled Release Society
Philipp HellerMatthias Barz

Abstract

Therapeutic nucleic acids such as pDNA hold great promise for the treatment of multiple diseases. These therapeutic interventions are, however, compromised by the lack of efficient and safe non-viral delivery systems, which guarantee stability during blood circulation together with high transfection efficiency. To provide these desired properties within one system, we propose the use of reactive triblock copolypept(o)ides, which include a stealth-like block for efficient shielding, a hydrophobic block based on reactive disulfides for cross-linking and a cationic block for complexation of pDNA. After the complexation step, bifunctional cross-linkers can be employed to bio-reversibly stabilize derived polyplexes by disulfide bond formation and to introduce endosomolytic moieties at the same time. Cross-linked polyplexes show no aggregation in human blood serum. Upon cellular uptake and cleavage of disulfide bonds, the cross-linkers can interact with the endosomal membrane, leading to lysis and efficient endosomal translocation. In principal, the approach allows for the combination of one polymer with various different cross-linkers and thus enables the fast forward creation of a polyplex library. Here, we provide a first insight ...Continue Reading

Citations

Dec 19, 2017·Chemical Communications : Chem Comm·R OtterP Besenius
Apr 11, 2019·Polymers·Philipp Michael KleinMatthias Barz
Sep 3, 2020·Polymers·Jose Rodrigo MaganaIlja K Voets
Apr 5, 2020·Advanced Drug Delivery Reviews·Franziska Freitag, Ernst Wagner
Feb 6, 2021·Macromolecular Bioscience·Irina AlbergRudolf Zentel
Dec 18, 2020·Advanced Drug Delivery Reviews·Yong Liu, Lichen Yin
Jul 31, 2019·Biomacromolecules·Yangwei DengMin-Hui Li

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.