Fe3O4@Au core-shell hybrid nanocomposite for MRI-guided magnetic targeted photo-chemotherapy.

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.

Magnetic Targeting of Magneto-Plasmonic Nanoparticles and Their Effects on Temperature Profile of NIR Laser Irradiated to CT26 Tumor in BALB/C Mice.

BACKGROUND: Photothermal therapy (PTT) is a promising method in the field of cancer hyperthermia. In this method, interaction between laser light and photosensitizer material, such as plasmonic nanoparticles, leads into a localized heating. Recent efforts in the area of PTT aim to exploit targeting strategies for preferential accumulation of plasmonic nanoparticles within the tumor. OBJECTIVE: To investigate the impact of magneto-plasmonic (Au@Fe2O3) nanoparticles on temperature profile of CT26 tumor, bearing mice were irradiated by NIR laser. MATERIAL AND METHODS: In this in vivo study, Au@Fe2O3 NPs were injected intraperitoneally to Balb/c mice bearing CT26 colorectal tumor. Immediately after injection, a magnet (magnetic field strength of 0.4 Tesla) was placed on the tumor site for 6 hours in order to concentrate nanoparticles inside the tumor. In the next step, the tumors were exposed with NIR laser source (808 nm; 2 W/cm2; 5 min). RESULTS: Tumor temperature without magnetic targeting increased ~7 ± 0.9 °C after NIR irradiation, whereas the tumors in magnetic targeted group experienced a temperature rise of ~12 ± 1.4 °C. CONCLUSION: It is concluded that Au@Fe2O3 nanoparticle is a good candidate for therapeutic nanostructure in cancer photothermal therapy.

Recent advances in ultrasound-triggered drug delivery through lipid-based nanomaterials.

The high prescribed dose of anticancer drugs and their resulting adverse effects on healthy tissue are significant drawbacks to conventional chemotherapy (CTP). Ideally, drugs should have the lowest possible degree of interaction with healthy cells, which would diminish any adverse effects. Therefore, an ideal scenario to bring about improvements in CTP is the use of technological strategies to ensure the efficient, specific, and selective transport and/or release of drugs to the target site. One practical and feasible solution to promote the efficiency of conventional CTP is the use of ultrasound (US). In this review, we highlight the potential role of US in combination with lipid-based carriers to achieve a targeted CTP strategy in engineered smart drug delivery systems.

Combined thermo-chemotherapy of cancer using 1 MHz ultrasound waves and a cisplatin-loaded sonosensitizing nanoplatform: an in vivo study.

PURPOSE: The aim of the present study was to develop a new strategy for combined thermo-chemotherapy of cancer. For this purpose, we used ultrasound waves [1 MHz; 1 W/cm2; 10 min] in combination with a sonosensitizing nanoplatform, named ACA, made of alginate co-loaded with cisplatin and gold nanoparticles (AuNPs). METHODS: Various combinatorial treatment regimens consisting of ultrasound, AuNPs, cisplatin, and ACA nanoplatform were studied in vivo. The CT26 colon adenocarcinoma cell line was used for tumor induction in BALB/c mice. During the ultrasound exposure, we monitored the temperature variations in each treatment group using infrared thermal imaging. Furthermore, tumor metabolism was assessed by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging. RESULTS: The combination of ultrasound with nanoplatform showed an improved therapeutic efficacy than free cisplatin or ultrasound alone. It was revealed that the examined thermo-chemotherapy protocol has the potential to intensively decrease the metabolic activity of CT26 tumors. CONCLUSIONS: The data obtained in this study confirmed a potent anti-tumor efficacy caused by the ACA nanoplatform and ultrasound combination. It may provide a beneficial cancer therapy strategy in which the thermal and mechanical effects of ultrasound can intensify the therapeutic ratio of conventional chemotherapy methods.

Simulation-guided photothermal therapy using MRI-traceable iron oxide-gold nanoparticle.

Despite the immense benefits of nanoparticle-assisted photothermal therapy (NPTT) in cancer treatment, the limited method and device for detecting temperature during heat operation significantly hinder its overall progress. Development of a pre-treatment planning tool for prediction of temperature distribution would greatly improve the accuracy and safety of heat delivery during NPTT. Reliable simulation of NPTT highly relies on accurate geometrical model description of tumor and determining the spatial location of nanoparticles within the tissue. The aim of this study is to develop a computational modeling method for simulation of NPTT by exploiting the theranostic potential of iron oxide­gold hybrid nanoparticles (IO@Au) that enable NPTT under magnetic resonance imaging (MRI) guidance. To this end, CT26 colon tumor-bearing mice were injected with IO@Au nanohybrid and underwent MR imaging. The geometrical model description of tumor and nanoparticle distribution map were obtained from MR image of the tumor and involved in finite element simulation of heat transfer process. The experimental measurement of tumor temperature confirmed the validity of the model to predict temperature distribution. The constructed model can help to predict temperature distribution during NPTT and then allows to optimize the heating protocol by adjusting the treatment parameters prior to the actual treatment operation.

Iron oxide-gold core-shell nano-theranostic for magnetically targeted photothermal therapy under magnetic resonance imaging guidance.

Recent efforts in the area of photothermal therapy (PTT) follow two important aims: (i) selective targeting of plasmonic nanoparticles to the tumor and (ii) real-time guidance of PTT operation through employing multimodal imaging modalities. In the present study, we utilized a multifunctional theranostic nanoplatform constructed from iron (III) oxide-gold (Fe2O3@Au) core-shell nanoparticles to fulfill these aims. The Au shell exhibits surface plasmon resonance, a property that is exploited to realize PTT. The magnetic core enables Fe2O3@Au to be employed as a magnetic resonance imaging (MRI) contrast agent. Furthermore, the magnetic core has the potential to establish a magnetic drug targeting strategy through which Fe2O3@Au can be directed to the tumor site by means of magnetic field. To test these potentials, Balb/c mice bearing CT26 colorectal tumor model were intravenously injected with Fe2O3@Au. Immediately after injection, a magnet was placed on the tumor site for 3 h to concentrate nanoparticles, followed by the near infrared (NIR) laser irradiation. MRI study confirmed the accumulation of nanoparticles within the tumor due to T2 enhancement capability of Fe2O3@Au. The in vivo thermometry results demonstrated that the tumors in magnetic targeting group had a significantly higher temperature elevation rate upon NIR irradiation than non-targeted group (~ 12 °C vs. 8.5 °C). The in vivo antitumor assessment revealed that systemic injection of Fe2O3@Au in combination with magnetic targeting and NIR irradiation resulted in complete remission of tumor growth. Therefore, Fe2O3@Au can establish a targeted PTT strategy for efficient eradication of tumor cells under the guidance of MRI.

A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy.

The current interest in cancer research is being shifted from individual therapy to combinatorial therapy. In this contribution, a novel multifunctional nanoplatform comprising alginate nanogel co-loaded with cisplatin and gold nanoparticles (AuNPs) has been firstly developed to combine photothermal therapy and chemotherapy. The antitumor efficacy of the as-prepared nanocomplex was tested against CT26 colorectal tumor model. The nanocomplex showed an improved chemotherapy efficacy than free cisplatin and caused a significantly higher tumor inhibition rate. The in vivo thermometry results indicated that the tumors treated with the nanocomplex had faster temperature rise rate under 532 nm laser irradiation and received dramatically higher thermal doses due to optical absorption properties of AuNPs. The combined action of chemo-photothermal therapy using the nanocomplex dramatically suppressed tumor growth up to 95% of control and markedly prolonged the animal survival rate. Moreover, tumor metabolism was quantified by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging and revealed that the combination of the nanocomplex and laser irradiation have the potential to eradicate microscopic residual tumor to prevent cancer relapse. Therefore, the nanocomplex can afford a potent anticancer efficacy whereby heat and drug can be effectively deliver to the tumor, and at the same time the high dose-associated side effects due to the separate application of chemotherapy and thermal therapy could be potentially reduced.

Gold nanoparticle-induced sonosensitization enhances the antitumor activity of ultrasound in colon tumor-bearing mice.

PURPOSE: As a noninvasive and nonionizing radiation, ultrasound can be focused remotely, transferring acoustic energy deep in the body, thereby addressing the penetration depth barrier of the light-based therapies. In cancer therapy, the effectiveness of ultrasound can be enhanced by utilizing nanomaterials that exhibit sonosensitizing properties called as nanosonosensitizers. The gold nanoparticle (AuNP) has been recently presented as a potent nanosonosensitizer with the potential to simultaneously enhance both the thermal and mechanical interactions of ultrasound with the tissue of the human body. Accordingly, this paper attempts to evaluate the in vivo antitumor efficiency of ultrasound in combination with AuNP. METHODS: BALB/c mice-bearing CT26 colorectal tumor model was intraperitoneally injected with AuNPs and then subjected to ultrasound irradiation (1 MHz; 2 W/cm2 ; 10 min) for three sessions. Furthermore, [18 F]FDG (2-deoxy-2-[18 F]fluoro-d-glucose) positron-emission tomography (PET) imaging was performed and the radiomic features from different feature categorizes were extracted to quantify the tumors' phenotype. RESULTS: The tumors were dramatically shrunk and the mice appeared healthy over 21 days of study span without the evidence of relapse. The animals treated with AuNP + ultrasound exhibited an obvious decline in tumor metabolic parameters such as standard uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) compared to other treatment groups. CONCLUSION: These findings support the use of AuNP as a potent sonosensitizing agent with the potential to use the thermal and mechanical effects of ultrasound so as to cause damage to the focused tumor site, resulting in an improved antitumor efficacy.

Alginate hydrogel co-loaded with cisplatin and gold nanoparticles for computed tomography image-guided chemotherapy.

The biomedical applications of gold nanoparticles (AuNPs) have experienced rapid growth in recent years, due to their expected benefits in medical imaging and therapy. In this work, we report the development of a theranostic nanocomplex constructed from alginate hydrogel co-loaded with cisplatin and AuNPs (abbreviated as ACA) for simultaneous drug delivery and computed tomography imaging. CT26 cells derived from mouse colon adenocarcinoma were exposed to various concentrations of ACA nanocomplex (for 24 h) and the cytotoxicity was measured using MTT assay. Moreover, the cells treated with ACA nanocomplex were imaged in a computed tomography scanner and the contrast enhancement due to the presence of nanocomplex was assessed. The cytotoxicity results showed that ACA nanocomplex had a more potent chemotherapy efficacy than free cisplatin, so that ACA nanocomplex at the concentration of 5 µg/ml (per cisplatin) and 20 µg/ml of free cisplatin resulted in the same cytotoxicity (survival rate: 66%). The computed tomography imaging study revealed that ACA nanocomplex increased the brightness of computed tomography images, the computed tomography number value, and contrast-to-noise ratio (CNR). ACA nanocomplex can be presented as a computed tomography-traceable nanocarrier that allows to monitor the delivery of therapeutics by assessing their localized accumulation and in vivo biodistribution.

The Measurement and Mathematical Analysis of 5-Fu Release from Magnetic Polymeric Nanocapsules, following the Application of Ultrasound.

OBJECTIVE: To study the effects of ultrasound irradiation on the release profile of 5-fluorouracil (5-Fu) loaded magnetic poly lactic co-glycolic acid (PLGA) nanocapsules. Also, the controlled drug-release behaviour of the nanocapsules was mathematically investigated. METHODS: The nanocapsules were synthesized, dispersed in phosphate buffered saline (PBS), transferred to a dialysis bag, and finally, irradiated by various ultrasound parameters (1 or 3MHz; 0.3-1W/cm2; 5-10 minutes). The release profile of the irradiated nanocapsules was recorded for 14 days. To find the in vitro drug release mechanism in the absence and presence of various intensities of ultrasound, the obtained data were fitted in various kinetic models for drug release. RESULTS: The results demonstrated that the ultrasound speeded up the rate of drug release from the nanocapsules. The mathematical analysis illustrated that when the ultrasound intensity is increased, the probability of controlled release behaviour of the nanocapsules is raised. We found that drug release from the irradiated nanocapsules follows an erosion-controlled mechanism with the decrease in the velocity of diffusion. CONCLUSION: In conclusion, to attain a controlled drug-delivery strategy in the area of cancer therapy, the drug release profile of the nano-carriers may be well-controlled by ultrasound.

Measurements of nanoparticle-enhanced heating from 1MHz ultrasound in solution and in mice bearing CT26 colon tumors.

Hyperthermia is considered as a new approach for cancer therapy. Non-selectivity of tissue heating in conventional hyperthermia methods results in collateral damages to healthy tissues and this is the greatest obstacle against hyperthermia in clinic. Herein, to promote the efficiency of conventional hyperthermia methods, nanoparticle-enhanced heating from 1MHz ultrasound was investigated in vitro and in vivo. The experiments were conducted on two mediums; (1) various colloidal nano-solutions (in vitro section) and (2) CT26 mouse colon carcinoma tumor loaded by various nanoparticles (in vivo section). Experiments in this study were designed to evaluate and compare the sonosensitizing potentials of gold nanoparticles (AuNPs), iron oxide nanoparticles (IONPs), and nano-graphene oxide (NGO) in enhancement of ultrasound-induced heat generation. The temperature profile of the solutions and the animal tumors containing nanoparticles were recorded during sonication. An increased heating rate during sonication was observed for both in vitro and in vivo mediums when the nanoparticles were present. Our in vitro experiments revealed that percentages of increases in temperature elevation rates were 12.5%, 20.4%, and 37.5% for IONPs, NGO, and AuNPs, respectively. Compared to the nanoparticles-free tumors, direct injection of AuNPs, NGO and IONPs into the tumors and subsequent sonication for 10min caused an increased temperature elevation rate of 37.5%, 24.1% and 16.1%, respectively. AuNPs, IONPs and NGO are proposed as ultrasound responsive nanomaterials with the potential of focusing the energy of acoustic waves on the tumor and inducing localized hyperthermia.

Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia.