Papers by rasoul irajirad
Research Square (Research Square), May 22, 2023
Background: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to... more Background: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high e ciency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) e cient photothermal transduction agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods: This study aimed to develop a three-dimensional nite element method (FEM) model for in vivonano-photothermal therapy (NPTT) in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) les of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. Results: The photothermal conversion e ciency (η) of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17°C observed at the hottest point on the surface of the tumor-bearing mice for 300 seconds of laser exposure at a power density of 1.4 W/cm². Furthermore, the highest level of tissue damage, with a maximum value of Ω=0.4, was observed in the intratumoral (IT) group, as determined through a simulation study. Conclusions: Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further re nement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning.
DOAJ (DOAJ: Directory of Open Access Journals), Oct 1, 2021
Objective(s): Successful detection of tumors in the early stages can significantly increase a pat... more Objective(s): Successful detection of tumors in the early stages can significantly increase a patient’s healing process and recovery speed. Conventional imaging techniques usually depend on the tissues’ anatomical structure. Epidermal growth factor receptor-2 (HER-2) is a transmembrane protein with an extracellular ligand-binding domain. HER2 plays an essential role in cell proliferation, differentiation, and survival, and its overexpression is associated with various cancers, especially breast and ovarian cancers. Access to its extracellular domain makes HER2 an ideal target for drug preparation and molecular imaging probes. In this study, a targeted magnetic nanoprobe for molecular imaging of HER2 positive cancers was synthesized, and also its potential as a T2-weighted targeted contrast agent was assessed.Materials and Methods: Superparamagnetic SPION nanoparticles were synthesized using the co-precipitation method in the presence of CMD and were labeled with SLTVSPWY peptide. The SPION@CMD@SLTVSPWY nanocomplex was characterized by TEM, DLS, XRD, AAS, FTIR, EDX, and VSM. The r1 and r2 relaxivities were then calculated using a 1.5 Tesla clinical magnetic field. The cytotoxicity of the nanocomplex was evaluated by MTT assay. Finally, the difference between uptake of targeted nanocomplexes and SPION by the human SKOV-3 cell line (HER2 +) was investigated.Results: The SPION@CMD NPs were synthesized with spherical shape and superparamagnetic behavior. Characterization results confirmed the formation of SPION@CMD@SLTVSPWY. r2 relaxivity and r2/r1 calculations resulted in suitable values of 313 mM-1s-1 and 8.05 for SPION@CMD@SLTVSPWY, respectively. Increased uptake of targeted nanocomplexed (SPION@CMD@SLTVSPWY) compared to non-targeted NPs (SPION@CMD) was very noticeable visually, and its numerical ratio was 3.51 at a concentration of 0.075 mM. Conclusion: The targeted synthesized nanocomplex in this study has great potential as a T2 weighted probe contrast agent in MR imaging owing to its appropriate high uptake in HER2 + cells.
Magnetic Resonance Materials in Physics Biology and Medicine, Mar 6, 2023
Artificial Cells Nanomedicine and Biotechnology, Oct 10, 2017
This study reports the synthesis and characterization of poly(ethylene glycol) coated gold@iron o... more This study reports the synthesis and characterization of poly(ethylene glycol) coated gold@iron oxide core-shell nanoparticles conjugated with folic acid (FA-PEG-Au@IONP). Also, targeted therapeutic properties of such a nanocomplex were studied on human nasopharyngeal carcinoma cell line KB and human breast adenocarcinoma cell line MCF-7 in vitro. The synthesized nanocomplex was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-Vis spectroscopy, vibrating sample magnetometry (VSM), and Fourier transform infrared (FTIR) spectroscopy. The photothermal effects of nanocomplex on both KB and MCF-7 cell lines were studied. Cell death and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry using an annexin V-fluorescein isothiocyanate/propidiumiodide apoptosis detection kit. It was found that nanocomplex is spherical in shape and its size is approximately 60 nm. UV-vis spectrum showed that nanocomplex has appropriate absorption near infrared region. FTIR spectra obtained from nanocomplex before and after conjugation with FA confirmed the formation of folate conjugated nanocomplex. Significant cell lethality was observed for KB ($62%) and MCF-7 ($33%) cells following photothermal therapy. Also, it was found that majority of the cell deaths were related to apoptosis process. It can be concluded that, the synthesized nanocomplex is an effective and promising multifunctional nanoplatform for targeted photothermal therapy of cancer.
Cancer Nanotechnology, Jun 14, 2023
Background: As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadv... more Background: As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadvantageous in that it confers a rather high toxicity and low longitudinal comfort time (r 1). We hypothesized that gadolinium when combined with gold-coated iron oxide nanoparticles (NPs), might deliver better radiosensitization in MRI-based cancer theranostics. After being synthesized ligand/receptor RGD@Fe 3 O 4-Au/Gd nanoparticles, they were characterized via some methods, such as visible-ultraviolet spectroscopy (UV-VIS), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscope (TEM). Using relaxometry, the parameters of contrast change in T 1-weighted MRI and the rate of radiation sensitivity on cancerous (MCF-7, SK-BR-3 and MDA-MB-231 (and reference (MCF-10a) breast cell lines were investigated. Results: The presence of ultra-small iron oxide, gold, gadolinium, and RGD peptide as components of the RGD@Fe 3 O 4-Au/Gd nanocomplex was confirmed by UV-visible, FTIR, EDX and XRD tests. With a size ranging from 4.124 nm (DLS) to 15 nm (TEM), these NPs exhibited a surface charge of-45.7 mV and a magnetic saturation of 3 emu/g. The concentrations of iron, gadolinium and gold samples in the nanocomplex were 1000, 1171 and 400 parts per million (ppm), respectively. In the relaxometry test, the rates of r 2 /r 1 and r 1 NPs were 1.56 and 23.5 mM −1 s −1. The dose increase factor for targeted (RGD@Fe 3 O 4-Au/Gd) and non-targeted (Fe 3 O 4-Au/Gd) NPs at 6 MV and 2 Gy was 89.1 and 59.1, respectively. Conclusion: Owing to an enhanced signal-to-noise ratio (SNR), as confirmed by the MRI of RGD receptor-expressing MDA-MB-231 cells, RGD@Fe 3 O 4-Au/Gd NPs were found to confer higher radiosensitization and an overall better performance as a novel radiosensitizer for MRI-based breast cancer theranostics than Fe 3 O 4-Au/Gd nanocomplex.
ChemMedChem, Mar 19, 2022
Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effe... more Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor‐infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran‐coated superparamagnetic iron oxide nanoparticles (SPIONs‐DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs‐DEX to an anti‐CD3 monoclonal antibody via cyanogen bromide as a cross‐linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs‐DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T2*‐weighted and T2‐weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non‐invasive assessment of TILs to identify patients eligible for immunotherapy.
Nanotheranostics, 2022
Recent years have seen considerable progress in the development of nanomedicine by the advent of ... more Recent years have seen considerable progress in the development of nanomedicine by the advent of 2D nanomaterials serving as ideal platforms to integrate multiple theranostic functions. We synthesized multifunctional stimuli-responsive 2D-based smart nanocomposites (NCs), comprising gold nanoparticles (AuNPs) and superparamagnetic iron oxides (SPIOs) scaffolded within graphene oxide (GO) nanosheets, coated with doxorubicin (DOX)-loaded 1-tetradecanol (TD), and further modified with an alginate (Alg) polymer. TD is a phase-change material (PCM) that confines DOX molecules to the GO surface and melts when the temperature exceeds its melting point (Tm=39 °C), causing the PCM to release its drug payload. By virtue of their strong near-infrared (NIR) light absorption and high photothermal conversion efficiency, GO nanosheets may enable photothermal therapy (PTT) and activate a phase change to trigger DOX release. Upon NIR irradiation of NCs, a synergistic thermo-chemotherapeutic effect can be obtained by GO-mediated PTT, resulting an accelerated and controllable drug release through the PCM mechanism. The biodistribution of these NCs could also be imaged with computed tomography (CT) and magnetic resonance (MR) imaging in vitro and in vivo. Hence, this multifunctional nanotheranostic platform based on 2D nanomaterials appears a promising candidate for multimodal image-guided cancer therapy.
Research Square (Research Square), Aug 25, 2022
Gadolinium-based contrast agents (GdCAs) have been the most frequently used T 1-weighted magnetic... more Gadolinium-based contrast agents (GdCAs) have been the most frequently used T 1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r 1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T 1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd 2 O 3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T 1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r 1 value (42.28 mM − 1 S − 1) and low relaxivity ratio (r 2 /r 1 : 1.416) at 3.0 T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely-used T 1-weighted CA. The cytotoxicity assay and histological examination con rmed the biocompatibility of FG-HNPs. The biodistribution study, transmission electron microscopy (TEM) and Prussian blue (PB) staining of tumor tissue proved the effective tumor localization of FG-HNPs. Therefore, FG-HNPs can be suggested as a promising CA for T 1-weighted MRI of tumors by virtue of their remarkable relaxivities and high biocompatibility.
Applied Nanoscience, Jun 17, 2022
BioMedical Engineering OnLine
Background Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to ... more Background Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) fil...
Magnetic Resonance Imaging
Cancer Nanotechnology
Background As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadva... more Background As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadvantageous in that it confers a rather high toxicity and low longitudinal comfort time (r1). We hypothesized that gadolinium when combined with gold-coated iron oxide nanoparticles (NPs), might deliver better radiosensitization in MRI-based cancer theranostics. After being synthesized ligand/receptor RGD@Fe3O4-Au/Gd nanoparticles, they were characterized via some methods, such as visible–ultraviolet spectroscopy (UV–VIS), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscope (TEM). Using relaxometry, the parameters of contrast change in T1-weighted MRI and the rate of radiation sensitivity on cancerous (MCF-7, SK-BR-3 and MDA-MB-231 (and reference (MCF-10a) breast cell lines were investigated. Results The presence of ultra-small iron oxide, gold, gadolinium, and RGD peptide as components of the RGD@Fe3O4-Au/Gd nanocomplex was c...
Cell journal, Feb 1, 2023
Objective: Increasing research has been focused on the development of various nanocomplexes as ta... more Objective: Increasing research has been focused on the development of various nanocomplexes as targeted contrast media in diagnostic modalities, mainly in computed tomography (CT) scan imaging. Herein, we report a new method that uses Triptorelin [a luteinizing hormone-releasing hormone (LHRH) agonist]-targeted gold nanoparticles (AuNPs) via alginate for early detection of cancer by molecular CT imaging. Materials and methods: In the experimental study, the formed multifunctional AuNPs coated with alginate conjugated with Triptorelin peptide (Triptorelin-Alginate-AuNPs) were synthesized and characterized via different techniques, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and fourier transform infrared (FTIR) spectroscopy. The MTT assay was applied to calculate the toxicity of the NPs. Results: The results indicated that the formed Triptorelin-Alginate-AuNPs with an Au core size of ~18 nm are noncytotoxic at 127-, 254-, 381- and 508-mM concentrations and revealed significant improvement in the attenuation of X-rays intensity and contrast to noise ratio (CNR), compared with non-targeted cells at the highest energies (90, 120, 140 kVp). At 90 kVp, compared to non-targeted cells, targeted cells (Triptorelin-Alginate-AuNPs) enable 1.58, 1.69, 3.7 and 3.43 times greater contrast at a concentration of 127 mM, 254 mM, 381 mM, and 508 mM, respectively. Conclusion: These results suggest that the developed Triptorelin-Alginate-AuNPs may be considered an effective contrast agent for molecular CT imaging of gonadotropin-releasing hormone (GnRH) receptor-expressing cancer cells.
Magnetic Resonance Materials in Physics, Biology and Medicine
Cancer Nanotechnology
Gadolinium-based contrast agents (GdCAs) have been the most frequently used T1-weighted magnetic ... more Gadolinium-based contrast agents (GdCAs) have been the most frequently used T1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd2O3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r1 value (42.28 mM−1S−1) and low relaxivity ratio (r2/r1: 1.416) at 3.0T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely used T1...
DOAJ (DOAJ: Directory of Open Access Journals), Sep 12, 2022
Objective: Recently, development of multifunctional contrast agent for effective targeted molecul... more Objective: Recently, development of multifunctional contrast agent for effective targeted molecular computed tomography (CT) imaging of cancer cells stays a major problem. In this study, we explain the ability of Triptorelin peptide-targeted multifunctional bismuth nanoparticles (Bi2S3@ BSA-Triptorelin NPs) for molecular CT imaging. Materials and Methods: In this experimental study, the formed nanocomplex of Bi2S3@ BSA-Triptorelin NPs was characterized using different methods. The MTT cytotoxicity test was performed to determine the appropriate concentration of nanoparticles in the MCF-7 cells. The X-ray attenuation intensity and Contrast to Noise Ratio (CNR) of targeted and non-targeted nanoparticles were measured at the concentrations of 25, 50, and 75 µg/ml and X-ray tube voltages of 90, 120 and 140 kVp. Results: We showed that the formed Bi2S3@ BSA-Triptorelin NPs with a Bi core size of approximately ~8.6 nm are nontoxic in a given concentration (0-200 µg/ml). At 90, 120, and 140 tube potentials (kVp), the X-ray attenuation of targeted cells were 1.35, 1.36, and 1.33-times, respectively, more than non-targeted MCF-7cells at the concentration of 75 μg/ml. The CNR values at 90, 120, and 140 kVp tube potentials were 171.5, 153.8 and 146.3 c/ϭ, respectively. Conclusion: These findings propose that the diagnostic nanocomplex of Bi2S3@ BSA-Triptorelin NPs can be applied as a good contrast medium for molecular CT techniques.
Nanotheranostics
Recent years have seen considerable progress in the development of nanomedicine by the advent of ... more Recent years have seen considerable progress in the development of nanomedicine by the advent of 2D nanomaterials serving as ideal platforms to integrate multiple theranostic functions. We synthesized multifunctional stimuli-responsive 2D-based smart nanocomposites (NCs), comprising gold nanoparticles (AuNPs) and superparamagnetic iron oxides (SPIOs) scaffolded within graphene oxide (GO) nanosheets, coated with doxorubicin (DOX)-loaded 1-tetradecanol (TD), and further modified with an alginate (Alg) polymer. TD is a phase-change material (PCM) that confines DOX molecules to the GO surface and melts when the temperature exceeds its melting point (Tm=39 °C), causing the PCM to release its drug payload. By virtue of their strong near-infrared (NIR) light absorption and high photothermal conversion efficiency, GO nanosheets may enable photothermal therapy (PTT) and activate a phase change to trigger DOX release. Upon NIR irradiation of NCs, a synergistic thermo-chemotherapeutic effect can be obtained by GO-mediated PTT, resulting an accelerated and controllable drug release through the PCM mechanism. The biodistribution of these NCs could also be imaged with computed tomography (CT) and magnetic resonance (MR) imaging in vitro and in vivo. Hence, this multifunctional nanotheranostic platform based on 2D nanomaterials appears a promising candidate for multimodal image-guided cancer therapy.
Lasers in Medical Science
The combination of multiple therapeutic and diagnostic functions is fast becoming a key feature i... more The combination of multiple therapeutic and diagnostic functions is fast becoming a key feature in the area of clinical oncology. The advent of nanotechnology promises multifunctional nanoplatforms with the potential to deliver multiple therapeutics while providing diagnostic information simultaneously. In this study, novel iron oxide-gold core–shell hybrid nanocomposites (Fe3O4@Au HNCs) coated with alginate hydrogel carrying doxorubicin (DOX) were constructed for targeted photo-chemotherapy and magnetic resonance imaging (MRI). The magnetic core enables the HNCs to be detected through MRI and targeted towards the tumor using an external magnetic field, a method known as magnetic drug targeting (MDT). The Au shell could respond to light in the near-infrared (NIR) region, generating a localized heating for photothermal therapy (PTT) of the tumor. The cytotoxicity assay showed that the treatment of CT26 colon cancer cells with the DOX-loaded HNCs followed by laser irradiation induced a significantly higher cell death as opposed to PTT and chemotherapy alone. The in vivo MRI study proved MDT to be an effective strategy for targeting the HNCs to the tumor, thereby enhancing their intratumoral concentration. The antitumor study revealed that the HNCs can successfully combine chemotherapy and PTT, resulting in superior therapeutic outcome. Moreover, the use of MDT following the injection of HNCs caused a more extensive tumor shrinkage as compared to non-targeted group. Therefore, the as-prepared HNCs could be a promising nanoplatform for image-guided targeted combination therapy of cancer.
ChemMedChem, 2022
Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effe... more Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor‐infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran‐coated superparamagnetic iron oxide nanoparticles (SPIONs‐DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs‐DEX to an anti‐CD3 monoclonal antibody via cyanogen bromide as a cross‐linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs‐DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T2*‐weighted and T2‐weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could ...
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Papers by rasoul irajirad