Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors

Abstract

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe3O4 and NiFe2O4 nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T2WI) signals and T2 values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.

Selective Photo-Assisted Eradication of Triple-Negative Breast Cancer Cells through Aptamer Decoration of Doped Conjugated Polymer Nanoparticles

“…In order to tip up aptamers to the CPN surface, we used modified NH 2 -terminated aptamers, and two functional amphiphilic polystyrene-based polymers (PS-PEG-COOH and PSMA) incorporated in a ~20% mass ratio in the synthesis of CNPs. The comb-like PS-PEG-COOH was previously employed by our group with the aim of increasing the colloidal stability of the resulting nanoparticles for biological experiments [ 18 , 22 ], and in this opportunity the carboxyl groups added to the surface of CPNs will subsequently allow for the formation of the amide bond through EDC coupling with the proposed aptamers. Alternatively, polystyrene-based polymer PSMA, which is also included in the same mass ratio into CPNs, is hydrolyzed in the aqueous environment after CPN synthesis to generate carboxyl groups in the surface for the further EDC coupling reaction.…”

“…[ 18 , 19 , 20 ]. Additionally, CPN biocompatibility in vitro and in vivo has been reported, which encouraged us to continue evaluating this type of nanomaterial for clinical use [ 19 , 21 , 22 ]. In accordance with the development of CPNs that specifically target cancer cells, thus reducing adverse side effects while improving therapeutic efficacy, different approaches have been considered to conjugate these types of nanoparticles to highly selective recognition molecules, such as antibodies or peptides, against cell-membrane receptors overexpressed on cancer cells [ 23 , 24 , 25 ].…”

Emerging Nanomaterials in Healthcare

“…Bioimaging is also important for in-vivo monitoring of various responses during disease treatment more especially when using targeted therapy approach [46]. Currently, imaging techniques widely used include X-ray imaging [47], magnetic resonance [48], fluorescence [49], luminescence [50], photoacoustics [51], radionuclides [52], and mass spectrometry [53].…”

Progress and Viewpoints of Multifunctional Composite Nanomaterials for Glioblastoma Theranostics

“…MRI is sensitive and can easily find small tumors that cannot be seen by CT [8]. In addition to MRI diagnosis, optical analysis is also considered to be another noninvasive diagnostic method [9]. However, due to the limitation of the depth of light, the current light source that can penetrate the brain skull tissue and perform treatment and diagnosis is near-infrared.…”