pH-triggered delivery of magnetic nanoparticles depends on tumor volume

Pershina, Alexandra G.; Brikunova, Olga Ya.; Demin, A. M.; Shevelev, Oleg B.; Разумов, И. А.; Zavjalov, Evgenii L.; Malkeyeva, Dina; Kiseleva, Elena; Krakhmal, N. V.; Вторушин, С. В.; Yarnykh, Vasily L.; Иванов, В. В.; Плешко, Р. И.; Краснов, В. П.; Огородова, Л. М.

doi:10.1016/j.nano.2019.102086

Cited by 20 publications

(12 citation statements)

References 26 publications

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“…We chose a strategy of covalent binding PEG molecules to the MNP surface. For this, we used a bifunctional PEG derivative with an active ester group capable of reacting with NH 2 groups on the MNP-SiO 2 -APS surface and a maleimide group capable of interacting with the mercapto group on the N -terminus of pHLIP. ,, Sequential conjugation of PEG and pHLIP with APS-modified MNPs was performed according to Scheme b.…”

Section: Resultsmentioning

confidence: 99%

“…To measure the amount of MNPs uptaken by a cell, ferrozine test was applied. Ferrozine test solution was prepared according to the previously described protocol …”

Section: Methodsmentioning

confidence: 99%

“…The peptides capable of forming an α-helix and incorporating into the cell membrane under mild acidolysis conditions with pH slightly <7.0 constitute the so-called class of pH-low insertion peptides (pHLIPs). , Taking into account that acidolysis is the hallmark of malignant solid tumors, , pHLIPs can be successfully used as targeting molecules for delivery of drugs, , MNP-based contrast probes, − Gd-modified polymeric nanoparticles, gold nanoparticles, and silica nanoparticles to tumor tissues.…”

Section: Introductionmentioning

confidence: 99%

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Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Demin

Pershina

Минин

et al. 2021

ACS Appl. Mater. Interfaces

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Magnetic Fe3O4 nanoparticles (MNPs) are often used to design agents enhancing contrast in magnetic resonance imaging (MRI) that can be considered as one of the efficient methods for cancer diagnostics. At present, increasing the specificity of the MRI contrast agent accumulation in tumor tissues remains an open question and attracts the attention of a wide range of researchers. One of the modern methods for enhancing the efficiency of contrast agents is the use of molecules for tumor acidic microenvironment targeting, for example, pH-low insertion peptide (pHLIP). We designed novel organosilicon MNPs covered with poly(ethylene glycol) (PEG) and covalently modified by pHLIP. To study the specific features of the binding of pHLIP-modified MNPs to cells, we also obtained nanoconjugates with Cy5 fluorescent dye embedded in the SiO2 shell. The nanoconjugates obtained were characterized by transmission electron microscopy (TEM), attenuated total reflection (ATR), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), dynamic light scattering (DLS), UV and fluorescence spectrometry, thermogravimetric analysis (TGA), CHN elemental analyses, and vibrating sample magnetometry. Low cytotoxicity and high specificity of cellular uptake of pHLIP-modified MNPs at pH 6.4 versus 7.4 (up to 23-fold) were demonstrated in vitro. The dynamics of the nanoconjugate accumulation in the 4T1 breast cancer orthotopically grown in BALB/c mice and MDA-MB231 xenografts was evaluated in MRI experiments. Biodistribution and biocompatibility studies of the obtained nanoconjugate showed no pathological change in organs and in the blood biochemical parameters of mice after MNP administration. A high accumulation rate of pHLIP-modified MNPs in tumor compared with PEGylated MNPs after their intravenous administration was demonstrated. Thus, we propose a promising approach to design an MRI agent with the tumor acidic microenvironment targeting ability.

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Section: Resultsmentioning

confidence: 99%

“…To measure the amount of MNPs uptaken by a cell, ferrozine test was applied. Ferrozine test solution was prepared according to the previously described protocol …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Demin

Pershina

Минин

et al. 2021

ACS Appl. Mater. Interfaces

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“…It is necessary to understand the mechanisms of the interactions of targeted theranostics nanomaterial with tumor cells and the tumor microenvironment. In addition, future nanosystems should be able to pass through biological barriers to reach any tumor sites of the body [46][47][48].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Comprehensive approach of hybrid nanoplatforms in drug delivery and theranostics to combat cancer

Thorat

Townley

Patil

et al. 2020

Drug Discovery Today

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To date, various chemically and biosynthesized nanoparticles, or hybrid nano systems, have been developed under the umbrella of nanomedicine. These may be introduced into the body either orally, nasally, intratumourally or intravenously . Successfully translating hybrid nanoplatforms from preclinical proof-of-concept to therapeutic value in the clinic is challenging. Having made significant advances with drug-delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. This review aims to identify gaps in our understanding of the current strengths of nanomedicine platforms in drug delivery and cancer theranostics. We report on the current approaches of nanomedicine at preclinical and clinical stages.

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“…One study [ 8 ] successfully transported magnetic nanoparticles to MDA-MB-231 human breast cancer xenografts by using pHLIP, indicating that the MDA-MB-231 breast cancer model has an acidic microenvironment and that pHLIP can target acidic tissues. Labeling pHLIP with radionuclides can target tumor tissues, and radionuclides can be retained in tumors to allow sufficient time to remove nontumor-binding markers from normal tissues, thereby yielding high-contrast images [ 6 , 9 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

An Experimental Study on [¹²⁵I]I-pHLIP (Var7) for SPECT/CT Imaging of an MDA-MB-231 Triple-Negative Breast Cancer Mouse Model by Targeting the Tumor Microenvironment

Sun

Yang

et al. 2021

Mol Imaging

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Objective. To evaluate the diagnostic efficacy of MDA-MB-231 triple-negative breast cancer with 125I-labeled pHLIP (Var7) by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. Methods. The binding fraction of [125I]I-pHLIP (Var7) and MDA-MB-231 cells was measured at pH 7.4 and pH 6.0, and tumor-bearing mice were subjected to small-animal SPECT/CT imaging studies. Results. At pH = 6.0 , the binding fractions of [125I]I-pHLIP (Var7) and MDA-MB-231 cells at 10 min, 40 min, 1 h, and 2 h were 1 .9 ± 0.1 %, 3.5 ± 0.1 %, 6.3 ± 0.8 %, and 6.6 ± 0.3 %, respectively. At pH = 7.4 , there was no measured binding between [125I]I-pHLIP (Var7) and MDA-MB-231 cells. Small-animal SPECT/CT imaging showed clearly visible tumors at 1 and 2 h after injection. Conclusions. [125I]I-pHLIP (Var7) could bind to MDA-MB-231 cells in an acidic environment, and small-animal SPECT/CT imaging showed clear tumors at 1 and 2 h after probe injection.

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pH-triggered delivery of magnetic nanoparticles depends on tumor volume

Cited by 20 publications

References 26 publications

Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Comprehensive approach of hybrid nanoplatforms in drug delivery and theranostics to combat cancer

An Experimental Study on [¹²⁵I]I-pHLIP (Var7) for SPECT/CT Imaging of an MDA-MB-231 Triple-Negative Breast Cancer Mouse Model by Targeting the Tumor Microenvironment

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pH-triggered delivery of magnetic nanoparticles depends on tumor volume

Cited by 20 publications

References 26 publications

Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI

Comprehensive approach of hybrid nanoplatforms in drug delivery and theranostics to combat cancer

An Experimental Study on [125I]I-pHLIP (Var7) for SPECT/CT Imaging of an MDA-MB-231 Triple-Negative Breast Cancer Mouse Model by Targeting the Tumor Microenvironment

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An Experimental Study on [¹²⁵I]I-pHLIP (Var7) for SPECT/CT Imaging of an MDA-MB-231 Triple-Negative Breast Cancer Mouse Model by Targeting the Tumor Microenvironment