A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

Nature Nanotechnology
Bryan Q SpringT Hasan

Abstract

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)--a multikinase inhibitor--encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.

References

Feb 21, 1996·Biochimica Et Biophysica Acta·D H ThompsonV C Anderson
Jan 1, 1996·Journal of Structural Biology·J R KremerJ R McIntosh
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Apr 14, 1999·Cell Death and Differentiation·D Kessel, Y Luo
Sep 24, 1999·Journal of the National Cancer Institute·L R DuskaT Hasan
Apr 27, 2001·Cancer Letters·K KurohaneN Oku
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jennifer TranRobert S Kerbel
Jun 20, 2002·Journal of the National Cancer Institute·Lynn HlatkyJudah Folkman
May 3, 2003·Cancer Cell·Selma PennacchiettiPaolo M Comoglio
Mar 9, 2005·International Journal of Radiation Oncology, Biology, Physics·Bin ChenTayyaba Hasan
Sep 27, 2005·Journal of Structural Biology·David N Mastronarde
Oct 20, 2005·Journal of the National Cancer Institute·Marcela G del CarmenTayyaba Hasan
May 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sergio DromiBradford J Wood
Jan 4, 2008·Circulation·Martin G Larson
Jul 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sung K ChangTayyaba Hasan
Sep 2, 2008·Nature Reviews. Drug Discovery·Mark E DavisDong M Shin
Jun 16, 2009·Nature Materials·Andre E NelMike Thompson
Nov 15, 2006·Medical Laser Application : International Journal for Laser Treatment and Research·David Kessel
Jul 8, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hedy Lee KindlerRichard M Goldberg
Sep 29, 2011·Gastroenterology·Chenwei LiDiane M Simeone
Jan 25, 2012·Nature Reviews. Cancer·Ermanno GherardiGeorge Vande Woude
May 12, 2012·Polymers·Hirenkumar K Makadia, Steven J Siegel
Sep 25, 2012·Nature Reviews. Cancer·Barbara Sennino, Donald M McDonald
Apr 12, 2013·Cancer Research·Barbara SenninoDonald M McDonald
Apr 26, 2013·Critical Reviews in Therapeutic Drug Carrier Systems·Daniel J Hines, David L Kaplan
Sep 5, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rossella EliseiSteven I Sherman
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Feb 27, 2014·British Journal of Cancer·M T HuggettS P Pereira
Feb 28, 2014·Proceedings of the National Academy of Sciences of the United States of America·Bryan Q SpringTayyaba Hasan
Apr 5, 2014·Nature Communications·Kevin A CarterJonathan F Lovell

❮ Previous
Next ❯

Citations

Sep 10, 2016·Journal of Drug Targeting·Jenifer Thewalt, D Peter Tieleman
Apr 21, 2017·Physical Chemistry Chemical Physics : PCCP·Julien MassiotVéronique Rosilio
May 16, 2017·Advanced Healthcare Materials·Dyego MirandaJonathan F Lovell
Jun 27, 2017·Nature Biomedical Engineering·Seok Hyun Yun, Sheldon J J Kwok
Apr 12, 2017·Advanced Materials·Pingqiang CaiXiaodong Chen
Jun 22, 2016·Nanoscale·Girgis ObaidTayyaba Hasan
Jul 26, 2017·ACS Applied Materials & Interfaces·Pengying WuXiaobing Wang
Nov 4, 2017·Chemical Communications : Chem Comm·Qingshuo MengYaping Li
Jan 26, 2018·Hepatic Oncology·Peter L LabibStephen P Pereira
Sep 28, 2018·Chemical Society Reviews·Yijing LiuXiaoyuan Chen
Apr 8, 2017·Journal of Biomechanical Engineering·Michael D NieskoskiBrian W Pogue
Jul 18, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hao XuJunle Qu
Jun 30, 2019·Journal of Biophotonics·Ramtin RahmanzadehGereon Hüttmann
Jan 3, 2020·Photochemistry and Photobiology·Aaron J SorrinImran Rizvi
Mar 7, 2020·Advanced Healthcare Materials·Samireh BadrigilanLobat Tayebi
Feb 16, 2017·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Y Lee, D H Thompson
Jan 21, 2017·Advanced Science·Dandan LuoJonathan F Lovell
Jan 5, 2017·The Korean Journal of Internal Medicine·Han Hee LeeTayyaba Hasan
Jan 9, 2018·Nanoscale·Layla Mohammad-HadiElnaz Yaghini
Apr 16, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Miloslav MacháčekJonathan F Lovell
Jun 15, 2019·Advanced Materials·Jingchao LiKanyi Pu
Aug 24, 2019·Journal of Clinical Medicine·Collin T InglutHuang-Chiao Huang
Mar 27, 2020·International Journal of Nanomedicine·Peter B BartosikMark Niedre

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
xenograft
biopsies
dynamic light scattering
electron microscopy
transmission electron microscopy
fluorescence imaging

Clinical Trials Mentioned

NCT01663272

Software Mentioned

VMD
GraphPad
MATLAB
IMOD
GraphPad Prism
Olympus
SerialEM
FluoView

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.