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Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications.

ABSTRACT: An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe(3+), gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3?nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

SUBMITTER: Liu F

PROVIDER: S-EPMC4918390 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications.

Liu Fuyao F He Xiuxia X Chen Hongda H Zhang Junping J Zhang Huimao H Wang Zhenxin Z

Nature communications 20150806

An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe(3+), gallic acid and poly(vinylpyrrolidone) at ambie ...[more]

PMID: 26245151

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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.

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Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications.

Publications

Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications.

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