Supporting data and methods for the characterization of iron oxide nanoparticles conjugated with pH-(low)-insertion peptide, testing their cytotoxicity and analyses of biodistribution in SCID mice bearing MDA-MB231 tumor
“…These findings suggest that these particles have a large surface area and are nanometer in size. In contrast to the other samples, the iron oxide Np sample had the highest surface area and had a very small particle size along with a strong adsorption property, according to the BET report 40 . Figure 8 N 2 adsorption–desorption graph with a variation of pore diameter with respect to dV/dlog(D).…”
The green synthesis of NPs through plant extracts can be a modest, one-pot alternative synthesis to the conventional physical or chemical method. The prime focus of this study is to produce MNPs by the reducing effect of Bauhinia tomentosa leaf extract, and it was immobilized in porcine pancreatic lipase (PPL). Synthesized NPs were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Raman spectroscopy, UV–Vis Spectrometry, Thermogravimetry, and Differential Scanning Calorimeter (DSC), Zeta potential test, VSM, BET and Fourier Transform Infrared Spectroscopy (FTIR). The effect of process parameters was studied, about the efficiency of immobilization are enzyme stability, the extent of enzyme reusability, its separation from products, the activity of immobilized enzyme, recovery, and its loss. Finally, the immobilized lipase was used for the synthesis of 1,3-diolein using enzyme-mediated esterification of oleic acid and glycerol. Under optimized condition (reaction temp-55 $$^\circ $$
∘
C; molar ratio-2.5:1; pH-7) diolein yield was achieved to be 94%. Therefore, this work was further used for the industrial production of 1,3-diacylglycerol since a perfect enzyme-catalyzed process was observed.
“…These findings suggest that these particles have a large surface area and are nanometer in size. In contrast to the other samples, the iron oxide Np sample had the highest surface area and had a very small particle size along with a strong adsorption property, according to the BET report 40 . Figure 8 N 2 adsorption–desorption graph with a variation of pore diameter with respect to dV/dlog(D).…”
The green synthesis of NPs through plant extracts can be a modest, one-pot alternative synthesis to the conventional physical or chemical method. The prime focus of this study is to produce MNPs by the reducing effect of Bauhinia tomentosa leaf extract, and it was immobilized in porcine pancreatic lipase (PPL). Synthesized NPs were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Raman spectroscopy, UV–Vis Spectrometry, Thermogravimetry, and Differential Scanning Calorimeter (DSC), Zeta potential test, VSM, BET and Fourier Transform Infrared Spectroscopy (FTIR). The effect of process parameters was studied, about the efficiency of immobilization are enzyme stability, the extent of enzyme reusability, its separation from products, the activity of immobilized enzyme, recovery, and its loss. Finally, the immobilized lipase was used for the synthesis of 1,3-diolein using enzyme-mediated esterification of oleic acid and glycerol. Under optimized condition (reaction temp-55 $$^\circ $$
∘
C; molar ratio-2.5:1; pH-7) diolein yield was achieved to be 94%. Therefore, this work was further used for the industrial production of 1,3-diacylglycerol since a perfect enzyme-catalyzed process was observed.
“…Blood samples were collected for biochemical analysis; tumor and organs (spleen, liver, heart, lung, kidney, and thymus) were collected for histopathological analysis and iron content determination using an iCAP 6300 Duo ICP spectrometer as described in ref . Small samples of the tumors were also collected and analyzed by TEM as described in ref . The biological sample collection and processing are described in detail in the Supporting Information.…”
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.
“…The 64 nm SPION-pHLIP nanoclusters exhibited the most effective pH-responsive retention in cells and gave a strong MR signal recorded in various animal tumor models ( Wei et al, 2017 ). In other work, Fe 3 O 4 magnetic NPs obtained by co-precipitation, modified by 3-aminopropylsilane (APS) (APS-MNP) and coated with pHLIP (pHLIP-MNP) to form NPs with 130–140 nm hydrodynamic diameters was investigated ( Pershina et al, 2020a ). T2 weighted MRI and distribution of Fe in breast tumors of different sizes revealed high targeting of small-to-medium sized tumors (80–400 cm 3 ) and less accumulation in larger tumors ( Pershina et al, 2020b ).…”
Section: Targeted Delivery Of Phlip-coated Nanomaterialsmentioning
The family of pH (Low) Insertion Peptides (pHLIP) comprises a tumor-agnostic technology that uses the low pH (or high acidity) at the surfaces of cells within the tumor microenvironment (TME) as a targeted biomarker. pHLIPs can be used for extracellular and intracellular delivery of a variety of imaging and therapeutic payloads. Unlike therapeutic delivery targeted to specific receptors on the surfaces of particular cells, pHLIP targets cancer, stromal and some immune cells all at once. Since the TME exhibits complex cellular crosstalk interactions, simultaneous targeting and delivery to different cell types leads to a significant synergistic effect for many agents. pHLIPs can also be positioned on the surfaces of various nanoparticles (NPs) for the targeted intracellular delivery of encapsulated payloads. The pHLIP technology is currently advancing in pre-clinical and clinical applications for tumor imaging and treatment.
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