Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery.

Chemical Science
Gayathri R EdiriweeraKristofer J Thurecht

Abstract

There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile in vivo, as well as reducing side-effects for an increased standard of care. Hence, it is crucial to engineer new materials that allow for a better understanding of the in vivo pharmacokinetic/pharmacodynamic behaviours of therapeutics. We have expanded on recent "click-to-release" bioorthogonal pro-drug activation of antibody-drug conjugates (ADCs) to develop a modular and controlled theranostic system for quantitatively assessing site-specific drug activation and deposition from a nanocarrier molecule, by employing defined chemistries. The exploitation of quantitative imaging using positron emission tomography (PET) together with pre-targeted bioorthogonal chemistries in our system provided an effective means to assess in real-time the exact amount of active drug administered at precise sites in the animal; our methodology introduces flexibility in both the targeting and therapeutic components that is specific to nanomedicines and offers unique advantages over other technologies. In this approach, the in vivo click reaction facilitates pro-drug activation as ...Continue Reading

References

Apr 20, 2006·Bioorganic & Medicinal Chemistry Letters·Michel AzoulayJean-Claude Florent
Mar 7, 2008·Journal of the American Chemical Society·Maksim RoyzenJoseph M Fox
Apr 1, 2008·Nanomedicine·Baran Sumer, Jinming Gao
Nov 13, 2008·Bioconjugate Chemistry·Elisa García GarayoaP August Schubiger
Apr 22, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Ronald Boellaard
Aug 29, 2009·Angewandte Chemie·Ellen M Sletten, Carolyn R Bertozzi
Jul 22, 2010·Angewandte Chemie·Katrin KnopUlrich S Schubert
May 24, 2011·Journal of the American Chemical Society·Michael T TaylorJoseph M Fox
Aug 13, 2011·Bioconjugate Chemistry·Sneha S Kelkar, Theresa M Reineke
Feb 19, 2013·Chemical Communications : Chem Comm·Daniel J ColesKristofer J Thurecht
Mar 28, 2013·Journal of Drug Delivery·Stefano Salmaso, Paolo Caliceti
Oct 5, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Raffaella RossinMarc S Robillard
Nov 28, 2013·Angewandte Chemie·Ron M VersteegenMarc S Robillard
Dec 7, 2013·Theranostics·Bing BaiPeter S Conti
Dec 24, 2013·Biochimica Et Biophysica Acta·Fan YangSteven Henikoff
Jul 12, 2014·Chemical Communications : Chem Comm·Helen L EvansEric O Aboagye
Sep 23, 2014·Chemistry & Biology·Craig S McKay, M G Finn
Dec 20, 2014·MAbs·Karin TaylorStephen M Mahler
May 26, 2015·Expert Opinion on Biological Therapy·Junnan TangKe Cheng
Nov 22, 2015·Pharmacological Reviews·Paul Polakis
Feb 9, 2016·Current Cancer Drug Targets·Fatemeh Sheikhi MehrabadiRainer Haag
Feb 18, 2016·Nature Chemical Biology·Jie Li, Peng R Chen
Jun 11, 2016·Advanced Healthcare Materials·Christopher B HowardKristofer J Thurecht
Jun 17, 2016·Bioconjugate Chemistry·Raffaella RossinMarc S Robillard
Oct 30, 2016·Angewandte Chemie·Xinyuan FanPeng R Chen
Oct 28, 2016·Bioconjugate Chemistry·Jan-Philip MeyerBrian M Zeglis
Nov 12, 2016·Nature Reviews. Cancer·Jinjun ShiOmid C Farokhzad
May 16, 2017·Molecular Pharmaceutics·James C KnightBart Cornelissen
Jul 1, 2017·Chemical Society Reviews·B L OliveiraG J L Bernardes
Feb 1, 2018·Journal of the American Chemical Society·Jonathan C T CarlsonRalph Weissleder
Mar 6, 2018·Molecular Pharmaceutics·Rosemery MembrenoBrian M Zeglis
Feb 1, 2015·Chemical Science·Siddharth S MatikondaAllan B Gamble
Sep 8, 2018·Nature Nanotechnology·Matthew FariaFrank Caruso

❮ Previous
Next ❯

Citations

Jul 14, 2020·Macromolecular Rapid Communications·Nathan R B Boase
Aug 9, 2020·Macromolecular Rapid Communications·Nicholas L FletcherKristofer J Thurecht
Dec 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yayue WangPing Feng
Apr 17, 2021·ACS Pharmacology & Translational Science·E Johanna L StéenMatthias M Herth
Nov 5, 2021·Macromolecular Bioscience·Chengbin YangChih-Kuang Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
imaging technique
amidation
column chromatography
flow cytometry
MDA
xenografts
confocal microscopy
xenograft

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.

Related Papers

ACS Chemical Biology
David M PattersonJennifer A Prescher
Current Opinion in Chemical Biology
David M Patterson, Jennifer A Prescher
Current Opinion in Chemical Biology
Hui-Wen ShihJennifer A Prescher
Accounts of Chemical Research
Carolyn R Bertozzi
© 2021 Meta ULC. All rights reserved