6 research outputs found

    Ultrasound responsive Gd-DOTA/doxorubicin-loaded nanodroplet as a theranostic agent for magnetic resonance image-guided controlled release drug delivery of melanoma cancer

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    Theranostic agents use simultaneous for diagnostic and therapeutic procedures. In the present study, the effect of Gd-DOTA/doxorubicin-loaded perfluorohexane nanodroplets as a theranostic nanoparticle for control released drug delivery and ultrasound/MR imaging was investigated on B16F10 melanoma cancer cells. The intracellular uptake was performed by inductively coupled plasma optical emission spectrometry (ICP-OES) that indicated sonicated Gd-DOTA/DOX@PFH NDs uptake by cancer cells was approximately 1.5 times more than the nonsonicated nanodroplets after 12 h. In vitro and in vivo toxicity assays revealed that synthesized NDs are biocompatible and do not have organ toxicity. Ultrasound exposure significantly enhanced the release of doxorubicin from NDs (P-value < 0.05). Ultrasound echogenicity and T1-MRI relaxometry indicated that synthesized NDs have strong ultrasound signal intensity and high r1 relaxivity (6.34 mM(-1) S-1). The concentration of DOX in mice vital organs for Gd-DOTA/DOX NDs was significantly lower than that of free DOX. Doxorubicin concentration after 150 min in the tumor region for the DOX-loaded Gd-NDs+US group reached 14.8 mu g/g followed by sonication, which was 2.3 fold higher than that of the non-sonicated group. According to the obtained results, the synthesized nanodroplets, with excellent diagnostic (ultrasound/MRI) and therapeutic properties, could be promising theranostic agents in cancer imaging and drug delivery for chemotherapeutic application

    Sonodynamic therapy of the breast cancer cells (4T1) using gold nanoclusters-loaded ultrasound-activated nanodroplets

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    Sonodynamic therapy (SDT) has been developed as a new approach to non-invasive cancer treatment. Nanoparticles (NPs) as sonosensitizers can enhance the efficiency of this method. In this study, bovine serum albumin-functionalized gold nanoclusters (BSA-AuNCs) were loaded in synthesized perfluorohexane nanodroplets (PFH NDs) stabilized by an alginate shell. The characterization results showed that AuNCs/PFH NDs had an appropriate size, good ζ-potential, and excellent stability for biological applications. Loading AuNCs as a sonosensitizer in ultrasound-activated NDs can enhance ultrasound therapy efficiency. The rough surface of AuNCs enhances the probability of cavitation by ultrasound waves which induces biological effects. Ultrasound (US) imaging confirmed this strategy. According to US images, the AuNCs-loaded and unloaded NDs showed good echogenicity. However, the presence of gold nanoclusters in NDs structure significantly increased their echogenicity. The in vitro studies were performed on 4T1 breast cancer and L929 normal cells. The MTT assay indicated that the high biocompatibility of NDs. The results of cellular internalization of NDs by 4T1 cells showed that ultrasound can facilitate cellular uptake of AuNCs/PFH NDs approximately 2.6-fold more than non-sonicated samples. The results of SDT investigation using MTT, colony, and apoptosis assays showed that the therapeutic effect of ultrasound on cancer cells was enhanced in the presence of AuNCs-loaded NDs. In conclusion, AuNCs/PFH NDs with excellent properties can be used as a theranostic agent for ultrasound-guided and -activated sonodynamic therapy

    Superparamagnetic iron oxide nanoparticle-loaded nanodroplets for dual-modal ultrasound/magnetic resonance imaging-guided drug delivery

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    Recently, ultrasound-sensitive nanodroplets (NDs) have been developed as controlled-release drug delivery systems. However, the high pressure and frequency of ultrasound (US) waves were needed to induce acoustic droplet vaporization (ADV) for triggering drug release. In this study, folic acid (FA) targeted NDs with an alginate (Alg) shell containing methotrexate (MTX) as a chemotherapy drug and superparamagnetic iron oxide nanoparticles (SPIONs) as an ADV promotor and a magnetic resonance (MR) imaging contrast agent were successfully synthesized. The physicochemical properties of NDs including the size, morphology, ultrasound echogenicity, magnetic properties, MR relaxivity, and drug release patterns were evaluated. In vitro ultrasound imaging showed that NDs can generate highly echogenic microbubbles (MBs). Additionally, SPIONs/MTX ND with a relaxivity value of 87.59 mM−1 s−1 can act as a T2-weighted MRI contrast agent. Folate receptor-positive 4T1 cells and folate receptor-negative L929 cells were utilized. The cell experiments and blood cytotoxicity evaluations proved that SPIONs/MTX-FA NDs are highly biocompatible with no hemolytic activity. The cellular uptake of FA-functionalized NDs increased by 3.2-fold compared to that of non-functionalized NDs, and it was further enhanced, more than three times, after US exposure. The MTT assay demonstrated that the cell viability for ultrasound-exposed samples treated with SPIONs/MTX NDs was significantly decreased in comparison to blank NDs which is related to more drug release from NDs. It was concluded that SPIONs/MTX-FA NDs have significant potential as theranostic agents for dual-modal US/MRI-guided and acoustically-activated drug delivery

    The Effect of Folic Acid-Targeted Nanocarriers in Ultrasound Imaging-guided Sonodynamic Therapy of Human Cervical Carcinoma (HeLa): in vitro Study

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    Introduction: Theranostic nanocarriers can be used simultaneously for the diagnosis and treatment of cancer. In this study, the effect of dotarem-and doxorubicin-loaded nanodroplet as a theranostic agent for ultrasound-guided and-controlled release drug delivery on HeLa cervical cancer cells was investigated. Materials and Methods: Folic acid-targeted nanodroplets consisting of dotarm (Gd-DOTA) and doxorubicin (DOX) with alginate shells were synthesized and characterized. In this study, HeLa and L929 cell lines were used as cancer and normal cells, respectively. Intracellular uptake of nanocarriers was evaluated using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Doxorubicin release in response to ultrasound exposure and its effect on cancer treatment were investigated. Ultrasound imaging was performed to assess the ultrasound signal enhancement by nanodroplets. Results: The characterization results confirmed the successful synthesis of nanodroplets with desirable physicochemical properties. Cytotoxicity test showed that the synthesized nanodroplets had high biocompatibility for normal cells and induced more death in cancer cells (75.3 vs 62.1). This effect was enhanced under ultrasound exposure (51). The ICP-OES test showed that the uptake of Gd/DOX-loaded nanodroplets for sonicated cancer cells was approximately 1.5 times higher than that for non-sonicated cells after 12 h. The results showed that the ultrasound exposure significantly increased the doxorubicin release from nanodroplets (77.5 vs 2.1). Also, ultrasound imaging showed that perfluorohexane nanodroplets could enhance ultrasound signal intensity. Conclusion: According to the results, doxorubicin-and dotarem-loaded nanodroplets with proper diagnostic and therapeutic properties can be promising theranostic agents in ultrasound-guided and controlled drug delivery for sonodynamic therapy of cancer

    Ultrasound-guided chemoradiotherapy of breast cancer using smart methotrexate-loaded perfluorohexane nanodroplets

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    Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer
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