Heme Oxygenase 1-Targeted Hybrid Nanoparticle for Chemo- and Immuno-Combination Therapy in Acute Myelogenous Leukemia

Advanced Science
Seok-Beom YongYong-Hee Kim

Abstract

Acute myelogenous leukemia (AML) is a fatal blood cancer with high patient mortality. Daunorubicin and cytarabine are first-line chemotherapy for AML, with bone marrow transplantation in most cases. Recently, cancer immunotherapy has been challenged in AML and leukemia-niche myeloid cells are promising targets for the AML immunotherapy. Heme oxygenase 1 (HO1) is an antioxidative and cytoprotective enzyme inducing chemo-resistant AML and has been focused as an immune checkpoint molecule in tumor microenvironments. Herein, lipid-polymer hybrid nanoparticle (hNP) is loaded with tin mesoporphyrin (SnMP), a HO1-inhibitor, and non-covalently modified with an engineered antibody for leukemic cell-targeted delivery. HO1-inhibiting T-hNP (T-hNP/SnMP) enhances chemo-sensitivity in human leukemia cells. In a human AML-bearing orthotopic mouse model, intravenously injected T-hNP not only actively targets to human leukemia cells but passively targets to CD11b+ myeloid cells in a bone marrow niche. The T-hNP/SnMP enhances the chemo-therapeutic effect of daunorubicin and boosts immune response by reprogramming bone marrow myeloid cells resulting from the recruitment of the monocyte-lineage and induction of inflammatory genes. The ex vivo stud...Continue Reading

References

Jan 29, 2008·International Journal of Cancer. Journal International Du Cancer·Yoshiki MizukamiHideki Fujii
Jan 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kieran P O'DeaMasao Takata
Jun 19, 2010·Blood·Jacob M Rowe, Martin S Tallman
Jul 19, 2012·Biotechnology and Bioengineering·Kok Hong LimSheldon Park
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Oct 29, 2013·FEBS Letters·Chrisann Kyi, Michael A Postow
Jan 17, 2014·Science Translational Medicine·Daniel R GettsNicholas J C King
Jul 19, 2014·Immunity·Roy Noy, Jeffrey W Pollard
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Dec 24, 2015·Oxidative Medicine and Cellular Longevity·A L FurfaroM Nitti
Mar 5, 2016·Journal of Perinatology : Official Journal of the California Perinatal Association·V K BhutaniM J Maisels
Nov 5, 2016·Blood·Alejandra Gutiérrez-GonzálezPaloma Sánchez-Mateos
Jan 22, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Seok-Beom YongYong-Hee Kim
Aug 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Stephen E KurtzJeffrey W Tyner
Jan 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tamara MuliaditanJames N Arnold
Jan 31, 2018·Nature Nanotechnology·Ranit KedmiDan Peer
Feb 14, 2018·The Journal of Experimental Medicine·Curtis J PerrySusan M Kaech
Feb 14, 2018·The Journal of Experimental Medicine·Sabine HovesCarola H Ries
Apr 25, 2018·Nature Medicine·Mikhail BinnewiesMatthew F Krummel
May 20, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenquan OuJong Oh Kim
Aug 16, 2018·The New England Journal of Medicine·Lee Ratner, UNKNOWN the Authors
Aug 21, 2018·The New England Journal of Medicine·Keisuke Kataoka, Seishi Ogawa
Sep 12, 2018·The Journal of Experimental Medicine·Pierre-Louis LoyherAlexandre Boissonnas
Aug 10, 2019·Biomaterials·Seok-Beom YongYong-Hee Kim
Feb 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sophie A DusoswaJuan J Garcia-Vallejo

❮ Previous
Next ❯

Citations

Feb 12, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jaehyun KimYong-Hee Kim
Oct 9, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenxing GuZhiyuan Zhong
Sep 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ayeskanta MohantyIn-Kyu Park
Aug 9, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenxing GuZhiyuan Zhong

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
scanning electron microscopy
flow cytometry
Confocal microscopy
xenografts
FACS
electrophoresis
Assay

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.