← Back to Search
Multifunctional Albumin-MnO₂ Nanoparticles Modulate Solid Tumor Microenvironment By Attenuating Hypoxia, Acidosis, Vascular Endothelial Growth Factor And Enhance Radiation Response.
P. Prasad, C. Gordijo, A. Z. Abbasi, A. Maeda, Angela Ip, A. M. Rauth, R. Dacosta, X. Wu
Published 2014 · Biology, Medicine
Download PDFAnalyze on Scholarcy
Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME. Approaches so far have been limited to regulating hypoxia, acidosis, or ROS individually, without accounting for their interdependent effects on tumor progression and response to treatments. Hence we have engineered multifunctional and colloidally stable bioinorganic nanoparticles composed of polyelectrolyte-albumin complex and MnO2 nanoparticles (A-MnO2 NPs) and utilized the reactivity of MnO2 toward peroxides for regulation of the TME with simultaneous oxygen generation and pH increase. In vitro studies showed that these NPs can generate oxygen by reacting with H2O2 produced by cancer cells under hypoxic conditions. A-MnO2 NPs simultaneously increased tumor oxygenation by 45% while increasing tumor pH from pH 6.7 to pH 7.2 by reacting with endogenous H2O2 produced within the tumor in a murine breast tumor model. Intratumoral treatment with NPs also led to the downregulation of two major regulators in tumor progression and aggressiveness, that is, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the tumor. Combination treatment of the tumors with NPs and ionizing radiation significantly inhibited breast tumor growth, increased DNA double strand breaks and cancer cell death as compared to radiation therapy alone. These results suggest great potential of A-MnO2 NPs for modulation of the TME and enhancement of radiation response in the treatment of cancer.
This paper references
R.J. Gillies (2004)
DNA Double-Strand Break Repair as Determinant of Cellular Radiosensitivity to Killing and Target in Radiation Therapy
E. Mladenov (2013)
A microenvironmental model of carcinogenesis
R. Gatenby (2008)
Soon-Shiong, P. SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients
N Desai (2009)
Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery
E. Goldberg (2002)
Tumor Microvasculature and Microenvironment: Novel Insights Through Intravital Imaging in Pre‐Clinical Models
D. Fukumura (2010)
Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4
S. Rademakers (2010)
A novel glucose ENFET based on the special reactivity of MnO2 nanoparticles.
X. Luo (2004)
Preparation of MnO2 nanoparticles by directly mixing potassium permanganate and polyelectrolyte aqueous solutions
Yonglan Luo (2007)
Hydrogen peroxide in the human body
B. Halliwell (2000)
pH imaging. A review of pH measurement methods and applications in cancers.
R. Gillies (2004)
Toxicological considerations of clinically applicable nanoparticles
L. Yildirimer (2011)
Intracellular processing of proteins mediated by biodegradable polyelectrolyte capsules.
Pilar Rivera-Gil (2009)
Serganova, I. Real Time Imaging of HIF-1R Stabilization and Degradation
E. Moroz (2009)
Hypoxia and breast cancer: prognostic and therapeutic implications.
K. Lundgren (2007)
Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic potential of two murine cell lines
T. Kalliomäki (2004)
Toxicology and clinical potential of nanoparticles
L. Yildirimer (2011)
Cosolvent approach for solution-processable electronic thin films.
Zhaoyang Lin (2015)
Hemoglobin-based Oxygen Carriers Combined with Anticancer Drugs May Enhance Sensitivity of Radiotherapy and Chemotherapy to Solid Tumors
W. Wu (2009)
Angiogenesis in cancer and other diseases
P. Carmeliet (2000)
A novel combination chemotherapy integrating with intratumoral chemotherapy.
Lichun Yang (2009)
Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy.
M. López-Lázaro (2007)
Hypoxia: A key regulator of angiogenesis in cancer
D. Liao (2007)
Nab Technology: A Drug Delivery Platform Utilizing Endothelial Gp60 Receptor-Based Transport and Tumour-Derived SPARC for Targeting. Drug Delivery Rep
N Desai (2007)
Synthesis and characterization of ratiometric ion-sensitive polyelectrolyte capsules.
L. L. Del Mercato (2011)
Molecular aspects of tumour hypoxia
S. Rademakers (2008)
Real-Time Imaging of HIF-1α Stabilization and Degradation
E. Moroz (2009)
Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging
H. Zhang (2006)
Choline biosensors based on a bi-electrocatalytic property of MnO2 nanoparticles modified electrodes to H2O2
Yu-Hui Bai (2007)
Glucose‐Responsive Bioinorganic Nanohybrid Membrane for Self‐Regulated Insulin Release
C. Gordijo (2010)
Ion and pH sensing with colloidal nanoparticles: influence of surface charge on sensing and colloidal properties.
F. Zhang (2010)
The impact of O2 availability on human cancer
Jessica A. Bertout (2008)
Anti-Angiogenic Therapeutic Drugs for Treatment of Human Cancer
H. Wu (2008)
Multispectral fluorescence imaging to assess pH in biological specimens.
Matthew R. Hight (2011)
A Commensal Helicobacter sp. of the Rodent Intestinal Flora Activates TLR2 and NOD1 Responses in Epithelial Cells
Nadia Chaouche-Drider (2009)
Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects.
A. AlKilany (2009)
Principles of Cancer Management: Radiation Therapy
S. Hellman (1997)
Why Do Cancers
R. A. Gatenby (2004)
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
J. Forsythe (1996)
Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers.
Claire Peyratout (2004)
Ion andpH Sensingwith Colloidal Nanoparticles: Influence of Surface Charge on Sensing and Colloidal Properties. Chemphyschem
F. Zhang (2010)
Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel.
N. Desai (2006)
Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy.
G. Semenza (2012)
SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients.
N. Desai (2009)
Nab Technology : A Drug Delivery Platform Utilising Endothelial gp 60 Receptor-based Transport and Tumour-derived SPARC for Targeting I
N. Desai (2009)
Why do cancers have high aerobic glycolysis?
R. Gatenby (2004)
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
J. Chiche (2010)
pH-Dependent doxorubicin release from terpolymer of starch, polymethacrylic acid and polysorbate 80 nanoparticles for overcoming multi-drug resistance in human breast cancer cells.
A. Shalviri (2012)
BSA-templated MnO2 nanoparticles as both peroxidase and oxidase mimics.
X. Liu (2012)
Nanoparticle albumin bound (nab) technology: targeting tumors through the endothelial gp60 receptor and SPARC
N. Desai (2007)
Staining Patterns and Colocalization of Pimonidazole, HIF-1R, CAIX, LDH-5, GLUT-1, MCT1 and MCT4
Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements.
P. Vaupel (1991)
Winegarden, N. A.; et al. In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation
Developmental Changes in the Metabolic Network of Snapdragon Flowers
J. Muhlemann (2012)
Modification of Hypoxia-Induced Radioresistance in Tumors by the Use of Oxygen and Sensitizers.
Hypoxia and radiation therapy: past history, ongoing research, and future promise.
S. Rockwell (2009)
pH-induced coacervation in complexes of bovine serum albumin and cationic polyelectrolytes.
K. Kaibara (2000)
In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation
A. Maeda (2012)
This paper is referenced by
Dendritic organosilica nanospheres with large mesopores as multi-guests vehicle for photoacoustic/ultrasound imaging-guided photodynamic therapy.
Yuting Huang (2020)
Strategies based on metal-based nanoparticles for hypoxic-tumor radiotherapy
Chenyang Zhang (2019)
Hybrid Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Modulating Tumor Hypoxia.
A. Z. Abbasi (2016)
Hypoxia-responsive block copolymer radiosensitizers as anticancer drug nanocarriers for enhanced chemoradiotherapy of bulky solid tumors.
W. Yin (2018)
Oxygen Self-Sufficient Amphiphilic Polypeptide Nanoparticles Encapsulating BODIPY for Potential Near Infrared Imaging-guided Photodynamic Therapy at Low Energy
L. Liu (2018)
Modulating tumor hypoxia by nanomedicine for effective cancer therapy
Rana Jahanban-Esfahlan (2018)
Construction of Silica‐Based Micro/Nanoplatforms for Ultrasound Theranostic Biomedicine
Y. Zhou (2017)
Scavenging of reactive oxygen and nitrogen species with nanomaterials
Carolina A. Ferreira (2018)
Targeting epithelial-mesenchymal transition: Metal organic network nano-complexes for preventing tumor metastasis.
Jin-xuan Fan (2017)
Altered Cell Cycle Arrest by Multifunctional Drug-Loaded Enzymatically-Triggered Nanoparticles.
C. Huang (2016)
Advances in nanomaterials for treatment of hypoxic tumor
Mei-Zhen Zou (2020)
Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application.
Yongwei Hao (2016)
Functional Polymer Nanocarriers for Photodynamic Therapy
T. Li (2018)
Rational design of block copolymer self-assemblies in photodynamic therapy
M. Demazeau (2020)
Multifunctional Bi2WO6 Nanoparticles for CT-Guided Photothermal and Oxygen-free Photodynamic Therapy.
C. Zhang (2018)
Co-delivery of oxygen and erlotinib by aptamer-modified liposomal complexes to reverse hypoxia-induced drug resistance in lung cancer.
Fengqiao Li (2017)
Radionuclide I-131 Labeled Albumin-Paclitaxel Nanoparticles for Synergistic Combined Chemo-radioisotope Therapy of Cancer
Longlong Tian (2017)
Albumin-Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy.
Longlong Tian (2017)
Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy
Xiaohan Zhou (2020)
Breaking the Depth Dependence by Nanotechnology-Enhanced X-Ray-Excited Deep Cancer Theranostics.
W. Fan (2019)
Fucoidan-Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Co-Targeting Tumor Hypoxia and Angiogenesis
Sung-Won Shin (2018)
PB@Au Core-Satellite Multifunctional Nanotheranostics for Magnetic Resonance and Computed Tomography Imaging in Vivo and Synergetic Photothermal and Radiosensitive Therapy.
Yan Dou (2017)
Modulation of Hypoxia in Solid Tumor Microenvironment with MnO2 Nanoparticles to Enhance Photodynamic Therapy
W. Zhu (2016)
Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma
Mihaela Aldea (2016)
Hypoxia-responsive nanoparticles for tumor-targeted drug delivery.
Y. Li (2020)
Construction of Smart Manganese Dioxide‐Based All‐in‐One Nanoplatform for Cancer Diagnosis and Therapy
Xiangmei Liu (2020)
Manganese Dioxide Nanozymes as Responsive Cytoprotective Shells for Individual Living Cell Encapsulation.
W. Li (2017)
A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy
Y. Liu (2019)
A Cu9S5 nanoparticle-based CpG delivery system for synergistic photothermal-, photodynamic- and immunotherapy
Lulu Zhou (2020)
Generic synthesis of small-sized hollow mesoporous organosilica nanoparticles for oxygen-independent X-ray-activated synergistic therapy
W. Fan (2019)
Liposomes co-loaded with metformin and chlorin e6 modulate tumor hypoxia during enhanced photodynamic therapy
Xuejiao Song (2016)
Dual-Stage Light Amplified Photodynamic Therapy against Hypoxic Tumor Based on an O2 Self-Sufficient Nanoplatform.
Li-Han Liu (2017)See more