Online citations, reference lists, and bibliographies.
← Back to Search

Targeting Of Drug‐loaded Nanoparticles To Tumor Sites Increases Cell Death And Release Of Danger Signals

Magdalena Alev, Laura Egenberger, L. Mühleisen, Bianca Weigel, B. Frey, R. Friedrich, Marina Poettler, C. Alexiou, C. Janko
Published 2018 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
ABSTRACT Innovative strategies fighting cancer by inducing anti‐tumor responses from the immune system are urgently needed. Amongst others, chemotherapeutics from the class of the anthracyclines have been shown to induce death of cancer cells with immunogenic features and triggering immunogenic anti‐tumor responses. However, the patient's immune system often becomes severely impaired by the unspecific action of these cytotoxic drugs in systemic chemotherapy, preventing any effective immune reactions. To reduce systemic side effects and to accumulate the drug exclusively in the tumor region, we developed an iron oxide nanoparticle‐based system for the magnetically targeted delivery of mitoxantrone to the tumor, which has previously proven its long‐term therapeutic efficacy in tumor bearing rabbits. Here, we show in vitro that superparamagnetic iron oxide nanoparticles (SPIONs), loaded with the chemotherapeutic drug mitoxantrone, are able to induce cell death with immunogenic features and concomitant maturation of dendritic cells, comparable to the free drug, whereas unloaded nanoparticles are very biocompatible. We conclude that the targeted delivery of mitoxantrone to the tumor region might be a promising possibility to selectively modulate the tumor microenvironment and to locally stimulate immune responses against the tumor. Thus, SPIONs can be used as a platform to specifically bring immunogenic cell death inducers (e.g. mitoxantrone, hypericin, doxorubicin) to the tumor region by sparing the immune system from their toxic effects.
This paper references
10.1182/BLOOD.V98.3.548
Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine.
R. Stone (2001)
10.1124/dmd.106.013474
Differential Subcellular Distribution of Mitoxantrone in Relation to Chemosensitization in Two Human Breast Cancer Cell Lines
Sophie Vibet (2007)
10.2217/fon.15.198
Cytotoxic effects of chemotherapy on cancer and immune cells: how can it be modulated to generate novel therapeutic strategies?
C. Rébé (2015)
10.1002/AJH.10363
Early lymphopenia as a risk factor for chemotherapy‐induced febrile neutropenia
C. Choi (2003)
Toxicity of Mitoxantrone-loaded Superparamagnetic Iron Oxide Nanoparticles in a HT-29 Tumour Spheroid Model.
Annkathrin Hornung (2016)
10.1007/978-1-62703-383-1_1
Navigation to the graveyard-induction of various pathways of necrosis and their classification by flow cytometry.
C. Janko (2013)
Cytotoxic e ff ects of chemotherapy on cancer and immune cells : how can it be modulated to generate novel therapeutic strategies ?
M. M. Davis (2015)
10.1515/9783111548050-024
M
M. Sankar (1824)
10.1038/nrclinonc.2009.146
Cyclophosphamide and cancer: golden anniversary
A. Emadi (2009)
10.1007/s00418-011-0780-8
Visualization of superparamagnetic nanoparticles in vascular tissue using XμCT and histology
R. Tietze (2011)
10.4049/jimmunol.174.5.3087
Generation of an Optimized Polyvalent Monocyte-Derived Dendritic Cell Vaccine by Transfecting Defined RNAs after Rather Than before Maturation1
N. Schaft (2005)
10.4161/onci.28473
Screening of novel immunogenic cell death inducers within the NCI Mechanistic Diversity Set
A. Q. Sukkurwala (2014)
10.1007/s00262-002-0335-x
Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles
A. Ito (2003)
10.1038/cdd.2008.67
The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death
T. Panaretakis (2008)
Fig
M. Obeid (2007)
10.1186/s13014-015-0506-5
The in vitro immunogenic potential of caspase-3 proficient breast cancer cells with basal low immunogenicity is increased by hypofractionated irradiation
Bernhard Kötter (2015)
The intersection between DNA damage response and cell death pathways.
S. Nowsheen (2012)
10.1002/cncr.11882
Chemotherapy‐induced neutropenia
J. Crawford (2004)
10.1016/j.autrev.2009.11.016
Scent of dying cells: the role of attraction signals in the clearance of apoptotic cells and its immunological consequences.
L. Munoz (2010)
10.1016/j.bbrc.2015.08.022
Magnetic nanoparticle-based drug delivery for cancer therapy.
R. Tietze (2015)
10.3390/molecules201018016
Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids
Annkathrin Hornung (2015)
10.7774/cevr.2014.3.2.113
Dendritic cell-based therapeutic cancer vaccines: past, present and future
M. S. Ahmed (2014)
10.1016/0022-1759(95)00072-I
A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V.
I. Vermes (1995)
10.4161/21624011.2014.955691
Consensus guidelines for the detection of immunogenic cell death
O. Kepp (2014)
10.1007/s00262-007-0325-0
DC immunotherapy is highly effective for the inhibition of tumor metastasis or recurrence, although it is not efficient for the eradication of established solid tumors
Dae-Seog Lim (2007)
10.3109/08916934.2012.754433
UVB-irradiated apoptotic cells induce accelerated growth of co-implanted viable tumor cells in immune competent mice
R. Chaurio (2013)
10.4161/cc.8.22.10026
Chemotherapy induces ATP release from tumor cells
I. Martins (2009)
10.3390/ijms140815910
Magnetic Iron Oxide Nanoparticles for Multimodal Imaging and Therapy of Cancer
R. Thomas (2013)
10.1016/j.jconrel.2011.06.001
Targeted drug delivery to tumors: myths, reality and possibility.
Y. Bae (2011)
10.1038/s41467-017-01651-9
Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression
Jianqin Lu (2017)
10.1038/cdd.2013.84
Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments
H. Inoue (2014)
10.1200/JCO.1995.13.10.2530
Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy.
P. Sonneveld (1995)
10.1038/nprot.2006.238
Analysis of apoptosis by propidium iodide staining and flow cytometry
C. Riccardi (2006)
10.3390/vaccines3030662
Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy
Yuchen Fan (2015)
10.1038/nri2438
Immunotherapy of autoimmunity and cancer: the penalty for success
R. Caspi (2008)
Targeted drug delivery to tumors: myths
Y. H. Bae (2011)
determines the immunogenicity of chemotherapy - induced cancer cell death
K. Tani Inoue (2012)
10.1021/jp5026224
Superparamagnetic iron oxide nanoparticles as novel X-ray enhancer for low-dose radiation therapy.
S. Klein (2014)
10.2147/IJN.S94139
Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy
Po-Chin Liang (2016)
Treatment e ffi ciency of free and nanoparticle - loaded Mitoxantrone for magnetic drug targeting in multicellular tumor spheroids
C. Alexiou
10.1038/cdd.2013.48
Danger signalling during cancer cell death: origins, plasticity and regulation
Abhishek D Garg (2014)
10.3390/ijms16059368
Different Storage Conditions Influence Biocompatibility and Physicochemical Properties of Iron Oxide Nanoparticles
Jan Zaloga (2015)
10.1016/j.ijbiomac.2010.10.002
Interaction of mitoxantrone, as an anticancer drug, with chromatin proteins, core histones and H1, in solution.
Zahra Hajihassan (2011)
10.1158/0008-5472.CAN-10-2788
Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis.
G. Schiavoni (2011)
10.1088/0953-8984/18/38/S25
Determination of the magnetic particle distribution in tumour tissue by means of x-ray tomography
O. Brunke (2006)
10.1182/BLOOD-2006-10-054221
Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications.
R. Špíšek (2007)
The geriatric cancer patient: equal benefit from equal treatment.
L. Balducci (2001)
10.1016/j.ejpb.2016.01.017
Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting.
J. Zaloga (2016)
10.1101/cshperspect.a008748
Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion.
Amelia E. Hochreiter-Hufford (2013)
Inflammatory outcomes of apoptosis
P. Davidovich (2014)
10.1016/j.immuni.2013.03.003
Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells.
Y. Ma (2013)
10.1016/j.colsurfb.2017.09.057
Studies on the adsorption and desorption of mitoxantrone to lauric acid/albumin coated iron oxide nanoparticles.
J. Zaloga (2018)
10.1016/j.biomaterials.2016.06.032
Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy.
Xiao Zhao (2016)
Chemotherapy-induced neutropenia: risks
J. Crawford (2004)
10.1007/s00281-005-0200-z
Cellular immunotherapy: antigen recognition is just the beginning
D. Chen (2005)
Treatment e ffi ciency of free and nanoparticle - loaded Mitoxantrone for magnetic drug targeting in multicellular tumor spheroids
C. Alexiou
10.1200/JCO.1989.7.5.560
Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer.
I. C. Henderson (1989)
[Dendritic cell-based therapeutic cancer vaccines].
M. Rizzo (2016)
10.13172/2052-9554-1-2-717
No littering: the clearance of dead cells and leaking cellular contents and possible pathological complications
Jan Brauner (2013)
10.1126/SCIENCE.1071059
The Danger Model: A Renewed Sense of Self
P. Matzinger (2002)
10.7150/thno.11544
Magnetic Nanoparticles in Cancer Theranostics
O. Gobbo (2015)
10.3389/fimmu.2016.00035
Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE
A. Mahajan (2016)
10.7150/thno.5411
Superparamagnetic Iron Oxide Nanoparticles: Amplifying ROS Stress to Improve Anticancer Drug Efficacy
G. Huang (2013)
10.2174/09298673113206660281
HPMA copolymer-bound doxorubicin induces immunogenic tumor cell death.
M. Šírová (2013)
10.2147/IJN.S147464
Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
C. Pan (2018)
10.4161/auto.19009
Premortem autophagy determines the immunogenicity of chemotherapy-induced cancer cell death
I. Martins (2012)
10.1007/s00262-011-1184-2
Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin
Abhishek D Garg (2011)
10.2147/IJN.S68539
Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
J. Zaloga (2014)
10.1016/J.CLIM.2007.02.006
Damage associated molecular pattern molecules.
M. Lotze (2007)
10.4049/jimmunol.1203539
Profound Impairment of Adaptive Immune Responses by Alkylating Chemotherapy
Adam J. Litterman (2013)
10.1166/JNN.2015.10834
Doxorubicin-Hyaluronan Conjugated Super-Paramagnetic Iron Oxide Nanoparticles (DOX-HA-SPION) Enhanced Cytoplasmic Uptake of Doxorubicin and Modulated Apoptosis, IL-6 Release and NF-kappaB Activity in Human MDA-MB-231 Breast Cancer Cells.
D. Vyas (2015)
10.1038/ni1102-991
Cancer immunoediting: from immunosurveillance to tumor escape
Gavin P Dunn (2002)
10.3390/ijms14047341
Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes
C. Janko (2013)
10.1158/0008-5472.CAN-14-2538
Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge.
Amani Makkouk (2015)
Cytotoxic e ff ects of chemotherapy on cancer and immune cells : how can it be modulated to generate novel therapeutic strategies ?
M. M. Davis (2015)
10.1126/science.aad0779
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1
E. Vacchelli (2015)
10.1021/BI00336A034
Characteristics of the binding of the anticancer agents mitoxantrone and ametantrone and related structures to deoxyribonucleic acids.
J. Lown (1985)
10.1016/b978-0-12-384931-1.00016-7
P
J. Lackie (2013)
Doxorubicin-Hyaluronan conjugated superparamagnetic Iron oxide nanoparticles (DOX-HA-SPION) enhanced cytoplasmic uptake of doxorubicin and modulated apoptosis
D. Vyas (2015)
Interaction of mitoxantrone
Z. Hajihassan (2011)
10.1016/j.nano.2013.05.001
Efficient drug-delivery using magnetic nanoparticles--biodistribution and therapeutic effects in tumour bearing rabbits.
R. Tietze (2013)
10.1038/onc.2009.356
Immunogenic death of colon cancer cells treated with oxaliplatin
A. Tesnière (2010)
10.1016/0167-4781(88)90063-2
Characterization of the fluorescence of the antitumor agent, mitoxantrone.
D. Bell (1988)
10.1038/nature08296
Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance
M. Elliott (2009)
10.1515/hsz-2014-0164
Inflammatory outcomes of apoptosis, necrosis and necroptosis
P. Davidovich (2014)
10.3389/fimmu.2014.00560
The Progression of Cell Death Affects the Rejection of Allogeneic Tumors in Immune-Competent Mice – Implications for Cancer Therapy
R. Chaurio (2014)
10.1016/j.bbrc.2012.07.108
Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation.
S. Klein (2012)
Real-time cell analysis of human cancer cell lines after chemotherapy with functionalized magnetic nanoparticles.
Stephan Duerr (2012)
10.2174/1573406054368738
Topoisomerase enzymes as therapeutic targets for cancer chemotherapy.
G. Giles (2005)
10.1038/nm1523
Calreticulin exposure dictates the immunogenicity of cancer cell death
M. Obeid (2007)
10.1088/0953-8984/20/20/204152
Microcomputed tomography analysis of ferrofluids used for cancer treatment.
H. Rahn (2008)
10.2147/IJN.S38378
Nanodrugs: pharmacokinetics and safety
S. Onoue (2014)
10.1016/j.ijpharm.2015.05.032
Doxorubicin loaded magnetic gold nanoparticles for in vivo targeted drug delivery.
N. Elbialy (2015)
10.1515/ntrev-2013-0011
Magnetic nanoparticles for cancer therapy
Stephan Duerr (2013)
10.2174/157339406777934717
Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy.
Y. Wang (2006)



This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar