Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker

Abstract

Purpose Targeting doxorubicin (DOX) by means of single-walled carbon nanotube (SWCNT) nanocarriers may help improve the clinical utility of this highly active therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can potentially reduce the unnecessary side effects and provide enhanced theranostics. In the current study, the in vitro and in vivo efficacy of DOX-loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer model. Methods Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with or without DOX were synthetized and extensively characterized. Their biocompatibility was assessed in vitro in luciferase (Luc2)-expressing 4T1 (4T1-Luc2) murine breast cancer cells using TiterTACS™ Colorimetric Apoptosis Detection Kit (apoptosis induction), poly (ADP-ribose) polymerase (marker for DNA damage), and thiobarbituric acid-reactive substances (oxidative stress generation) assays, and the efficacy of DOX-loaded SWCNTs was evaluated by measuring the radiance efficiency using bioluminescence imaging (BLI). Tumor progression and growth were monitored after 4T1-Luc2 cells inoculation using noninvasive BLI and magnetic resonance imaging (MRI) before and after subsequent injection of SWCNT complexes actively and magnetically targeted to tumor sites. Results Significant increases in apoptosis, DNA damage, and oxidative stress were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in bioluminescence was observed in a dose- and time-dependent manner. Noninvasive BLI and MRI revealed successful tumor growth and subsequent attenuation along with metastasis inhibition following DOX-loaded SWCNTs injection. Magnetic tagging of SWCNTs was found to produce significant discrepancies in apparent diffusion coefficient values providing a higher contrast to detect treatment-induced variations as noninvasive imaging biomarker. In addition, it allowed their sensitive noninvasive diagnosis using susceptibility-weighted MRI and their magnetic targeting using an externally applied magnet. Conclusion Enhanced therapeutic efficacy of DOX delivered through antibody-conjugated magnetic SWCNTs was achieved. Further, the superiority of apparent diffusion coefficient measurements using diffusion-weighted MRI was found to be a sensitive imaging biomarker for assessment of treatment-induced changes.

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

“…Over the past decades, several nano-sized DDSs have been developed and applied by targeted drug delivery to cancer cells, such as liposomes, [4][5][6][7] polymeric micelles, [8][9][10][11] dendrimers, [12][13][14][15][16] carbon nanotubes, [17][18][19][20][21][22] inorganic nanoparticles, [23][24][25][26] and silica-based materials. [27][28][29][30][31] Among them, mesoporous silica nanoparticles (MSNs) have attracted much attention due to their unique physiochemical properties, such as large specific surface area and pore volume, controllable particle size, remarkable stability and biocompatibility, and high drug-loading capacity.…”

Carbon Nanomaterials for Breast Cancer Treatment

“…This would allow for reducing the drugs dosage, their concentrations on sites that are not of interest, and the side effects associated with chemotherapy and hormonal therapy [15,16]. In this regard, carbon nanomaterials with potential uses for the administration of drugs against cancer and breast cancer are being analyzed [17,22,23,[29][30][31]; they are considered as advantageous systems to control drug release in the organism and increase the efficiency of treatments and reduce their toxicity [17,32,33]. However, carbon nanomaterials have some disadvantages including their lack of solubility and low reproduction rate through their chemical functionalization and structural characterization.…”

“…Recent studies in nanomedicine concluded that fullerenes, CNTs, and graphene have favorable properties for the carriage, targeted, and controlled delivery of chemotherapeutical drugs including taxol (paclitaxel), docetaxel (DTX), doxorubicin (DOX), and others [22,29,31,32,44,[50][51][52][53]. Raza et al [22] reported that the system conformed by the fullerene C 60 and DTX (C 60 /DXT) is able to improve up to 4.2 times the bioavailability of DTX and decreases the clearance of DTX by 50%.…”

Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

“…Pure MWCNTs are diamagnetic [24] and their magnetic steerability must be achieved by combining with ferro-or superparamagnetic components [25][26][27], for example, by decoration with Fe 3 O 4 [28] or Fe encapsulation (at the stage of c-CVD synthesis or via capillary forces as a posttreatment) [29]. Indeed, as c-CVD is a convenient and tunable one-step synthesis of Fe@MWCNTs, we decided to focus on effective loading of Fe@MWCNTs with chemotherapeutics representing various mechanisms of cytotoxicity and to anchor the drugs using different chemical routes.…”