Biomimetic, Hypoxia-Responsive Nanoparticles Overcome Residual Chemoresistant Leukemic Cells with Co-Targeting of Therapy-Induced Bone Marrow Niches

被引：46

作者：

Dong, Xiao ^{[1
,2
]}

Mu, Li-Li ^{[3
]}

Liu, Xue-Liang ^{[1
,2
]}

Zhu, Hua ^{[4
]}

Yang, Si-Cong ^{[1
,2
]}

Lai, Xing ^{[1
,2
]}

Liu, Hai-Jun ^{[1
,2
]}

Feng, Hai-Yi ^{[1
,2
]}

Lu, Qin ^{[1
,2
]}

Zhou, Bin-Bing S. ^{[1
,2
]}

Chen, Hong-Zhuan ^{[5
]}

Chen, Guo-Qiang ^{[6
]}

Lovell, Jonathan F. ^{[7
]}

Hong, Deng-Li ^{[3
]}

Fang, Chao ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Hongqiao Int Inst Med, Tongren Hosp, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol & Chem Biol, Inst Med Sci, Shanghai 200025, Peoples R China

[3] SJTU SM, Key Lab Cell Differentiat & Apoptosis, Shanghai Key Lab Reprod Med, Minist Educ,Shanghai Inst Hematol,Ruijin Hosp,Dep, Shanghai 200025, Peoples R China

[4] SJTU SM, Key Lab Pediat Hematol & Oncol, Dept Hematol Oncol, Minist Hlth,Shanghai Childrens Med Ctr, Shanghai 200025, Peoples R China

[5] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Biomed Res, Shanghai 201210, Peoples R China

[6] SJTU SM, Key Lab Cell Differentiat & Apoptosis, Minist Educ, Dept Pathophysiol, Shanghai 200025, Peoples R China

[7] Univ Buffalo State Univ New York, Dept Biomed Engn, Buffalo, NY 14260 USA

来源：

ADVANCED FUNCTIONAL MATERIALS | 2020年 / 30卷 / 12期

基金：

中国国家自然科学基金;

关键词：

bone marrow; hypoxia responsive; leukemia; nanoparticles; niche; DRUG-DELIVERY; STEM-CELLS; FACTOR-I; CXCR4;

D O I：

10.1002/adfm.202000309

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemoresistance conferred by leukemia propagating cells (LPCs) in a therapy-induced niche (TI-niche) within the bone marrow is one of the main obstacles in leukemia treatment. Effective approaches to circumvent the TI-niche protection and to eliminate the resident LPCs remain to be exploited. Here, developed is a niche-targeted nanosystem using leukemic cell membrane-coated mesoporous silica nanoparticles (DA(azo)@CMSN) for co-delivering daunorubicin for leukemia cell chemotherapy and a TGF beta RII neutralizing antibody (aTGF beta RII) to block niche signaling. DA(azo)@CMSN effectively targets the TI-niche. Through an azobenzene-based hypoxia-responsive linker, sequential delivery of the two active molecules overcomes niche-mediated chemoresistance, attenuates systemic burden, and prolongs survival in a mouse model of leukemia. This work demonstrates a proof-of-principle for biomimetic and microenvironment-activated multiplexed nanoparticulate drug delivery strategies for overcoming therapy-induced chemoresistance in leukemia.

引用

页数：13

共 69 条

[1] Enhanced Antitumor Activity of the Photosensitizer meso-Tetra(N-methyl-4-pyridyl) Porphine Tetra Tosylate through Encapsulation in Antibody-Targeted Chitosan/Alginate Nanoparticles [J].

Abdelghany, Sharif M. ;

Schmid, Daniela ;

Deacon, Jill ;

Jaworski, Jakub ;

Fay, Francois ;

McLaughlin, Kirsty M. ;

Gormley, Julie A. ;

Burrows, James F. ;

Longley, Daniel B. ;

Donnelly, Ryan F. ;

Scott, Christopher J. .

BIOMACROMOLECULES, 2013, 14 (02) :302-310

[2] Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells [J].

Agarwal, Puneet ;

Isringhausen, Stephan ;

Li, Hui ;

Paterson, Andrew J. ;

He, Jianbo ;

Gomariz, Alvaro ;

Nagasawa, Takashi ;

Nombela-Arrieta, Cesar ;

Bhatia, Ravi .

CELL STEM CELL, 2019, 24 (05) :769-+

[3] Enhanced antiproliferative activity of Herceptin (HER2)-conjugated gemcitabine-loaded chitosan nanoparticle in pancreatic cancer therapy [J].

Arya, Geetanjali ;

Vandana, Mallaredy ;

Acharya, Sarbari ;

Sahoo, Sanjeeb K. .

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 2011, 7 (06) :859-870

[4] Combination of Imatinib with CXCR4 Antagonist BKT140 Overcomes the Protective Effect of Stroma and Targets CML In Vitro and In Vivo [J].

Beider, Katia ;

Darash-Yahana, Merav ;

Blaier, Orly ;

Koren-Michowitz, Maya ;

Abraham, Michal ;

Wald, Hanna ;

Wald, Ori ;

Galun, Eithan ;

Eizenberg, Orly ;

Peled, Amnon ;

Nagler, Arnon .

MOLECULAR CANCER THERAPEUTICS, 2014, 13 (05) :1155-1169

[5] Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models [J].

Benito, Juliana ;

Ramirez, Marc S. ;

Millward, Niki Zacharias ;

Velez, Juliana ;

Harutyunyan, Karine G. ;

Lu, Hongbo ;

Shi, Yue-Xi ;

Matre, Polina ;

Jacamo, Rodrigo ;

Ma, Helen ;

Konoplev, Sergej ;

McQueen, Teresa ;

Volgin, Andrei ;

Protopopova, Marina ;

Mu, Hong ;

Lee, Jaehyuk ;

Bhattacharya, Pratip K. ;

Marszalek, Joseph R. ;

Davis, R. Eric ;

Bankson, James A. ;

Cortes, Jorge E. ;

Hart, Charles P. ;

Andreeff, Michael ;

Konopleva, Marina .

CLINICAL CANCER RESEARCH, 2016, 22 (07) :1687-1698

[6] Bridging Bio-Nano Science and Cancer Nanomedicine [J].

Bjornmalm, Mattias ;

Thurecht, Kristofer J. ;

Michael, Michael ;

Scott, Andrew M. ;

Caruso, Frank .

ACS NANO, 2017, 11 (10) :9594-9613

[7]

Blair HA, 2018, DRUGS, V78, P1903, DOI 10.1007/s40265-018-1022-3

[8] Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia cells allows their remote activation [J].

Boto, Carlos ;

Quartin, Emanuel ;

Cai, Yijun ;

Martin-Lorenzo, Alberto ;

Garcia Cenador, Maria Begona ;

Pinto, Sandra ;

Gupta, Rajeev ;

Enver, Tariq ;

Sanchez-Garcia, Isidro ;

Hong, Dengli ;

das Neves, Ricardo Pires ;

Ferreira, Lino .

NATURE COMMUNICATIONS, 2017, 8

[9] Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers [J].

Bradstock, KF ;

Makrynikola, V ;

Bianchi, A ;

Shen, W ;

Hewson, J ;

Gottlieb, DJ .

LEUKEMIA, 2000, 14 (05) :882-888

[10] CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers [J].

Burger, J. A. ;

Peled, A. .

LEUKEMIA, 2009, 23 (01) :43-52

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