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

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.

Novel MR imaging nanoprobe for hepatocellular carcinoma detection based on manganese-zinc ferrite nanoparticles: in vitro and in vivo assessments.

PURPOSE: Achieving new contrast enhancer agents that can produce high-resolution images in magnetic resonance imaging (MRI) with a minimum dose and side effects has always been important. METHODS: Herein, the pegylated curcumin-coated manganese-zinc ferrite nanoparticles (MZF@CA-PEG-CUR NPs) have been reported as an MR imaging nanoprobe in hepatocellular carcinoma detection in the murine model for the first time. In vitro studies were done on HEPA 1-6 cancer cells and L929 as normal cells, and in vivo studies were done on hepatocellular carcinoma (HCC) using xenograft models of HCC. RESULTS: The prepared NP had a diameter of 105 nm with narrow size distribution and was superparamagnetic with a saturated magnetization (Ms) of 39 emu/g. The NP was biocompatible without any significant hemolysis and cytotoxicity. Prussian blue staining showed more cellular uptake of HEPA 1-6 compared to L929 control cells after incubation (P < 0.05). The concentration of Fe in mice blood confirmed the plasma half-life of about 3 h; it seems the PEGylation increased the circulation time. ICP-OES of Fe showed the highest tumor localization for MZF@CA-CUR-PEG NPs, due to passive accumulation, compared to the other mice studied organs. The r2 relaxivity of NPs was 134.89 mM- 1 s- 1, and in vitro MRI demonstrated better effects in HEPA 1-6 cells than in L929 (P < 0.05). Also, in vivo MR images showed signal enhancement efficacy in tumor-bearing mice. CONCLUSION: This study demonstrated that the MZF@CA-CUR-PEG nanoprobe could be a promising candidate as an MR imaging agent in hepatocellular carcinoma early detection.

Folic acid-functionalized gadolinium-loaded phase transition nanodroplets for dual-modal ultrasound/magnetic resonance imaging of hepatocellular carcinoma.

Dual-modal molecular imaging by combining two imaging techniques can provide complementary information for early cancer diagnosis and therapeutic monitoring. In the present manuscript, folic acid (FA)-functionalized gadolinium-loaded nanodroplets (NDs) are introduced as dual-modal ultrasound (US)/magnetic resonance (MR) imaging contrast agents. These phase-change contrast agents (PCCAs) with alginate (Alg) stabilizing shell and a liquid perfluorohexane (PFH) core were successfully synthesized via the nano-emulsion method and characterized. In this regard, mouse hepatocellular carcinoma (Hepa1-6) as target cancer cells and mouse fibroblast (L929) as control cells were used. The in vitro and in vivo cytotoxicity assessments indicated that Gd/PFH@Alg and Gd/PFH@Alg-FA nanodroplets are highly biocompatible. Gd-loaded NDs do not induce organ toxicity, and no significant hemolytic activity in human red blood cells is observed. Additionally, nanodroplets exhibited strong ultrasound signal intensities as well as T1-weighted MRI signal enhancement with a high relaxivity value of 6.40 mM-1 s-1, which is significantly higher than that of the clinical Gadovist contrast agent (r1 = 4.01 mM-1 s-1). Cellular uptake of Gd-NDs-FA by Hepa1-6 cancer cells was approximately 2.5-fold higher than that of Gd-NDs after 12 h incubation. Furthermore, in vivo results confirmed that the Gd-NDs-FA bound selectively to cancer cells and were accumulated in the tumor region. In conclusion, Gd/PFH@Alg-FA nanodroplets have great potential as US/MR dual-modal imaging nanoprobes for the early diagnosis of cancer.

Assessment of Manganese-Zinc Ferrite Nanoparticles as a Novel Magnetic Resonance Imaging Contrast Agent for the Detection of 4T1 Breast Cancer Cells.

BACKGROUND: The aim of the study was to evaluate the potential of manganese-zinc ferrite nanoparticles (MZF NPs) as a novel negative magnetic resonance imaging (MRI) contrast agents for 4T1 (mouse mammary carcinoma) and L929 (murine fibroblast) cell lines. METHODS: MZF NPs and its suitable coating, polyethylene glycol (PEG) via covalent bonding, were investigated under in vitro condition. The cytotoxicity of MZF NPs was tested by 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay after 12 and 24 h of incubation. To evaluate the potential of MZF NPs as T2 MRI nanocontrast agent, images were obtained from phantom containing different Fe concentrations and T2 relaxivity (r 2) was measured. The viability of both 4T1 breast cancer and L929 murine fibroblast cell lines incubated with different Fe concentrations. RESULTS: In vitro T2-weighted MRI showed that signal intensity of 4T1 cells was lower than that of L929 as control cells. T2-weighted MRI showed that signal intensity of MZF NPs enhanced with increasing concentration of NPs. The values of 1/T2 relaxivity (r 2) for coated MZF NPs with PEG found to be 85.5 mM-1 s-1 which is higher than that of commercially clinical used (Sinerem) MRI contrast agent. CONCLUSION: The results showed that MZF NPs have potential to detect breast cancer cells (4T1) and also have high contrast resolution between normal (L929) and cancerous cells (4T1) which is a suitable nanoprobe for T2-weighted MR imaging contrast agents.