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Magnetic nanoparticles coated with polyarabic acid demonstrate enhanced drug delivery and imaging properties for cancer theranostic applications.

ABSTRACT: Therapeutic targeting of tumor cells with drug nanocarriers relies upon successful interaction with membranes and efficient cell internalization. A further consideration is that engineered nanomaterials should not damage healthy tissues upon contact. A critical factor in this process is the external coating of drug delivery nanodevices. Using in silico, in vitro and in vivo studies, we show for the first time that magnetic nanoparticles coated with polyarabic acid have superior imaging, therapeutic, and biocompatibility properties. We demonstrate that polyarabic acid coating allows for efficient penetration of cell membranes and internalization into breast cancer cells. Polyarabic acid also allows reversible loading of the chemotherapeutic drug Doxorubicin, which upon release suppresses tumor growth in vivo in a mouse model of breast cancer. Furthermore, these nanomaterials provide in vivo contrasting properties, which directly compare with commercial gadolinium-based contrasting agents. Finally, we report excellent biocompatibility, as these nanomaterial cause minimal, if any cytotoxicity in vitro and in vivo. We thus propose that magnetic nanodevices coated with polyarabic acid offer a new avenue for theranostics efforts as efficient drug carriers, while providing excellent contrasting properties due to their ferrous magnetic core, which can help the future design of nanomaterials for cancer imaging and therapy.

SUBMITTER: Patitsa M

PROVIDER: S-EPMC5429723 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Magnetic nanoparticles coated with polyarabic acid demonstrate enhanced drug delivery and imaging properties for cancer theranostic applications.

Patitsa Maria M Karathanou Konstantina K Kanaki Zoi Z Tzioga Lamprini L Pippa Natassa N Demetzos Constantinos C Verganelakis Dimitris A DA Cournia Zoe Z Klinakis Apostolos A

Scientific reports 20170410 1

Therapeutic targeting of tumor cells with drug nanocarriers relies upon successful interaction with membranes and efficient cell internalization. A further consideration is that engineered nanomaterials should not damage healthy tissues upon contact. A critical factor in this process is the external coating of drug delivery nanodevices. Using in silico, in vitro and in vivo studies, we show for the first time that magnetic nanoparticles coated with polyarabic acid have superior imaging, therapeu ...[more]

PMID: 28396592

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Project description:BackgroundEngineered inorganic nanoparticles (NPs) are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent. We show that by changing the coating of magnetic iron oxide NPs using poly-L-lysine (PLL) polymer the colloidal stability of the dispersion is improved in aqueous solutions including water, phosphate buffered saline (PBS), PBS with 10% fetal bovine serum (FBS) and cell culture medium, and the internalization of the NPs toward living mammalian cells is profoundly affected.MethodsA multifunctional magnetic NP is designed to perform a near-infrared (NIR)-responsive remote control photothermal ablation for the treatment of breast cancer. In contrast to the previously reported studies of gold (Au) magnetic (Fe3O4) core-shell NPs, a Janus-like nanostructure is synthesized with Fe3O4 NPs decorated with Au resulting in an approximate size of 60 nm mean diameter. The surface of trisoctahedral Au-Fe3O4 NPs was coated with a positively charged polymer, PLL to deliver the NPs inside cells. The PLL-Au-Fe3O4 NPs were characterized by transmission electron microscopy (TEM), XRD, FT-IR and dynamic light scattering (DLS). The unique properties of both Au surface plasmon resonance and superparamagnetic moment result in a multimodal platform for use as a nanothermal ablator and also as a magnetic resonance imaging (MRI) contrast agent, respectively. Taking advantage of the photothermal therapy, PLL-Au-Fe3O4 NPs were incubated with BT-474 and MDA-MB-231 breast cancer cells, investigated for the cytotoxicity and intracellular uptake, and remotely triggered by a NIR laser of ~ 808 nm (1 W/cm2 for 10 min).ResultsThe PLL coating increased the colloidal stability and robustness of Au-Fe3O4 NPs (PLL-Au-Fe3O4) in biological media including cell culture medium, PBS and PBS with 10% fetal bovine serum. It is revealed that no significant (< 10%) cytotoxicity was induced by PLL-Au-Fe3O4 NPs itself in BT-474 and MDA-MB-231 cells at concentrations up to 100 μg/ml. Brightfield microscopy, fluorescence microscopy and TEM showed significant uptake of PLL-Au-Fe3O4 NPs by BT-474 and MDA-MB-231 cells. The cells exhibited 40 and 60% inhibition in BT-474 and MDA-MB-231 cell growth, respectively following the internalized NPs were triggered by a photothermal laser using 100 μg/ml PLL-Au-Fe3O4 NPs. The control cells treated with NPs but without laser showed < 10% cell death compared to no laser treatment control CONCLUSION: Combined together, the results demonstrate a new polymer gold superparamagnetic nanostructure that integrates both diagnostics function and photothermal ablation of tumors into a single multimodal nanoplatform exhibiting a significant cancer cell death.

Project description:The synthesis of self-assembled peptide nanoparticles using a facile one-pot synthesis approach is gaining increasing attention, allowing therapy in combination with diagnosis. Their drawback is limited diagnostic potential, which can be improved after necessary modifications and efficacious functionalization. Herein, a cyclic heptapeptide having the Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence was modified by conjugation of the ε-amino group of the terminal lysine residue with diethylenetriamine pentaacetic acid (DTPA) as a bifunctional chelating agent (BFC) for radiolabeling with a γ-emitting radionuclide (99mTc, half-life 6.01 h; energy 140 keV). Further, the free amino group of the middle lysine residue was successfully conjugated with near-infrared fluorescence (NIRF) dye Cyanine5.5 N-succinimidyl ester (Ex/Em = 670/701 nm) by a co-assembly method to form newly designed novel NIRF dye conjugated self-assembled peptide-DTPA (Cy5.5@SAPD) nanoparticles. The fluorescent nanoparticle formation was confirmed by using a fluorescence spectrophotometer (Ex/Em = 650/701 nm), and the transmission electron microscope (TEM) images showed a size of ∼ 40 nm with a lattice fringe distance of 0.294 nm. Cytotoxicity and confocal laser scanning microscopy (CLSM) studies showed that these nanoparticles possess a high affinity for the αvβ3-integrin receptor overexpressed on brain tumor glioblastoma with an EC50 = 20 μM. Moreover, these nanoparticles were observed to have potential to internalize into U87MG cells more prominently than HEK-293 cancer cells and induce apoptosis. The apoptosis assay showed 79.5% apoptotic cells after 24 h treatment of Cy5.5@SAPD nanoparticles. Additionally, these nanoparticles were also radiolabeled with 99mTc for the single photon emission computed tomography (SPECT) imaging study in tumor-bearing female Balb/c mice. The excellent imaging feature of Cy5.5@SAPD-99mTc nanoparticles as a multimodal (SPECT/NIRF) diagnostic probe, as well as noteworthy therapeutic potential was observed. The results suggested that our newly designed novel dual-targeting dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme.

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Magnetic nanoparticles coated with polyarabic acid demonstrate enhanced drug delivery and imaging properties for cancer theranostic applications.

Publications

Magnetic nanoparticles coated with polyarabic acid demonstrate enhanced drug delivery and imaging properties for cancer theranostic applications.

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