This review summarizes recent progress in the design and applications of cadmium-free quantum dots (Cd-free QDs), with an emphasis on their role in biophotonics and nanomedicine. We first present the features of Cd-free QDs and describe the physics and emergent optical properties of various types of Cd-free QDs whose applications are discussed in subsequent sections. Selected specific QD systems are introduced, followed by the preparation of these Cd-free QDs in a form useful for biological applications, including recent advances in achieving high photoluminescence quantum yield (PL QY) and tunability of emission color. Next, we summarize biophotonic applications of Cd-free QDs in optical imaging, photoacoustic imaging, sensing, optical tracking, and photothermal therapy. Research advances in the use of Cd-free QDs for nanomedicine applications are discussed, including drug/gene delivery, protein/peptide delivery, image-guided surgery, diagnostics, and medical devices. The review then considers the pharma...

New Generation Cadmium-Free Quantum Dots for Biophotonics and Nanomedicine

Biocompatible polymersomes-based cancer theranostics: Towards multifunctional nanomedicine.

Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis.

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Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy

Context Linalool (LL) is associated with numerous pharmacological activities. However, its poor solubility usually results in poor bioavailability, and further limited its applications.Objective To reduce volatilization and improve bioavailability of LL, linalool-loaded nanostructured lipid carriers (LL-NLCs) were prepared.Materials and methods LL-NLCs were prepared using high-pressure homogenization method and optimized via response surface methodology-central composite design, followed by characterization, including particle size (PS), zeta potential (ZP), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and in vitro release study. Rats were administered 300 mg × kg − 1 LL with each preparation (LL-NLCs or LL) via oral gavage.Results LL-NLCs had a PS of 52.72 nm with polydispersity index of 0.172, and ZP of –16.0 mV. The encapsulation efficiency and drug loading gave 79.563 and 7.555%, respectively. The cumulative release of LL from free LL...

Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers.

Effective therapies require an efficient method for drug delivery. The main goals of drug delivery systems, or carriers, is to enhance therapeutic efficiency by targeting specific tissue, and to provide control over the rate of drug release. Core–shell vesicle drug carriers are based on bilayer-forming amphiphiles: liposomes composed of phospholipid bilayers, polymersomes composed of copolymers, and niosomes from nonionic surfactants. Designed to carry hydrophilic drugs, they offer, in addition to targeting and controlled release, protection of drugs from degradation, prolonged circulation time in vivo, and administration routes that are incompatible with the unmodified drugs. Extensive studies link delivery efficiency to the carrier size, shape, and surface chemistry and charge, as well as environmental conditions (temperature, pH) and cell type. This review discusses the three types of formulations and summarizes studies of their performance in biomedical applications such as cancer therapy (tumor targeting) or transport through the blood–brain barrier (BBB).

Core–shell drug carriers: liposomes, polymersomes, and niosomes

ARTICLE; PHARMACEUTICAL BIOTECHNOLOGY Delivery of size-controlled long-circulating polymersomes in solid tumours, visualized by quantum dots and optical imaging in vivo

Introduction Ultra-short echo-time (UTE) imaging [1, 2] has recently been utilized to evaluate signal changes in lung parenchyma for various animal disease models [3, 4]. In addition, quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI has been performed for pulmonary embolism and tumor in humans [5, 6]. In a previous study, we reported that the signal intensity of UTE images in lung parenchyma and liver metastasis increased after conventional MR contrast agent administration [7]. Our group has also developed a multifunctional nanoprobe containing a positive MR contrast agent, a fluorescence dye and an anticancer drug, and succeeded in imaging drug delivery to subcutaneous and deep-seated tumors [8, 9]. As the next step, we applied the nanoprobes to lung tumors and other pulmonary diseases. In the present study, the signal changes in lung parenchyma with metastatic tumor after administration of nanoprobes containing manganese contrast agent were evaluated using UTE imaging.  Materials and Methods Female Balb/c nude mice (Japan SLC Inc., Shizuoka, Japan, n = 7) were used for in vivo experiments. Green fluorescence protein-overexpressed Colon 26 cancer cells (Anticancer Japan Inc., Osaka, 2.0 × 10 cells/100 μl) were administered via the tail vein to make metastasis models in the lung area. We confirmed using ex vivo fluorescence images that diffuse metastatic tumors developed in the lung area. In vivo MR experiments of the model mice were performed more than 7 days after the cell administration. The nanoprobe consisted of dextran modified with DTPA-chelated residue and bound manganese ions (Dextran-DTPA-Mn) (Figure 1). Binding with dextran-DTPA enables manganese ions to elude capture in the liver and remain in the blood circulation. In this paper, Dextran-DTPA-Mn (0.25mmol/kg, Molecular weight = 40,000) was administered via the tail vein to evaluate changes to the signal intensity of the lung with metastases for periods of at least 24 hours. MR images were acquired before, immediately, 12 and 24 hours after Dextran-DTPA-Mn administration. To compare the signal changes using conventional contrast agents, Gd-DTPA (Magnevist, Bayer Healthcare, Germany) (0.25 mmol/kg) was also administered via the tail vein. All MRI acquisitions were performed on a 7.0 Tesla animal MRI (Magnet: Kobelco, Japan; Console: Bruker Biospin, Germany). Measurements were made with a 35 mm inner-diameter transmit/receive volume coil (Rapid Biomedical, Germany). 3D-UTE images were acquired using the following parameters: TR/TE = 8/ 0.02 ms; flip angle = 10o; FOV = 38.4 mm × 38.4 mm × 44.8 mm; Matrix = 128 × 128 × 128; Projection number = 51360. T2-weighted images using a rapid acquisition with relaxation enhancement (RARE) sequence were also acquired to detect tumors in the lung. Imaging parameters were: TR/effective-TE = 2000/40 ms; FOV = 38.4 mm × 38.4 mm, Matrix = 256 × 256, RARE factor = 4. As an external reference for signal normalization, a tube containing 0.1 mM MnCl2 solution was placed beside the mouse during imaging. After the experiments, regions-of-interest in the lung that excluded blood-rich areas (such as the heart) were selected for the assessment of signal intensity.  Results and Discussion Figure 2 presents normalized 3D-UTE images of the lung before, immediately, 12 and 24 hours after Dextran-DTPA-Mn administration. The normalized signal was calculated by dividing the signal intensity in the lung area by the signal of the external reference. The normalized signal increased immediately after the administration and remained higher than the ratio before administration over 24 hours. Figure 3 compares the normalized signal in lung parenchyma after Dextran-DTPA-Mn (n = 4) and Gd-DTPA (n = 3) administration. The signals were normalized by the signal intensity before the administration. The normalized Dextran-DTPA-Mn signal was significantly higher than that using Gd-DTPA at immediately and 12 hours after the administration. Also, the normalized signal at 12 hours after Dextran-DTPA-Mn administration remained high. These results indicate that Dextran-DTPA-Mn remains in the bloodstream and tissue for long periods. Figure 4 compares a T2-weighted and 3D-UTE images in the lung area at 24 hours after Dextran-DTPA-Mn administration to a tumor model mouse at 10 days after tumor cell administration. Although T2-weighted images can detect the tumor in lung parenchyma (arrow), the signal intensity is poor due to the susceptibility difference with air. On the other hand, 3D-UTE images with Dextran-DTPA-Mn obtained strong signal throughout the entire lung tumor region even for the air-rich parenchyma (arrow). The tumor region became more conspicuous due to the accumulation of Dextran-DTPA-Mn, indicating the future possibility of early-stage disease detection using-3D UTE images combined with multifunctional nanoprobes such as our multimodal nanoprobe or Gd-DTPA/DACHPt-loaded micelles [8-10].  Acknowledgements The authors thank Miss Sayaka Shibata and Aiko Sekita for technical assistance during the in vivo experiments and Mr. Jeff Kershaw for technical advice and proofreading. This work was supported in part by the JSPS through the FIRST Program. References [1] Gewalt SL, et al: Magn Reson Med., 1993; 29: 99-106, [2] Shattuck MD, et al: Magn Reson Med., 1997; 38: 938-942, [3] Takahashi M, et al: J Magn Reson Imaging, 2010; 32: 326-333, [4] Togao O, et al: Magn Reson Med., 2010, 64: 1491-1498, [5] Hatabu H, et al: Mang Reson Med., 1996; 36: 503-508, [6] Pauls S, et al: Magn Reson Imaging, 2008; 26: 1334-1341, [7] Kokuryo D, et al: Proc. ISMRM 2011; 972, [8] Aoki I, et al: Proc. ISMRM 2008; 794, [9] Kokuryo D, et al: Proc ISMRM 2010; 461, [10] Kaida S, et al: Cancer Res. 2010; 70: 7031-7041.

Evaluation of Lung Metastatic Tumor Using Dextran-DTPA-Mn Nanoprobes with Ultra-Short Echo-Time Imaging

[Problem] To provide a water-soluble hyperbranch polymer which has satisfactory relaxing capability, does not undergo the dissociation of metal ions, and has excellent safety to living bodies and proper levels of water solubility and lipid solubility, and which has wide organ distribution and an effect of being taken into organs and therefore enables the imaging of a wide variety of target organs and a wide variety of diseases and can be used as a novel MRI imaging agent. [Solution] A hyperbranch polymer having a graft chain at the terminal of the molecule thereof, wherein both a segment (A) having a moiety capable of exerting paramagnetism and a segment (B) having at least one functional group selected from the group consisting of a carboxyl group, an amino group, a hydroxy group and a sulfo group are contained in the graft chain; and an MRI imaging agent comprising the hyperbranch.

Water-soluble hyperbranch polymer having paramagnetism

The present invention provides a safe polymer nanoparticle composite with few side effects, and an MRI contrast agent incorporating said polymer nanoparticle composite. The polymer nanoparticle composite is capable of specifically accumulating on a tumor tissue to selectively extract the tissue, exhibiting high contrast even when used in small amounts, and enabling imaging over prolonged periods of time. This polymer nanoparticle composite is characterized by containing a block copolymer that includes a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment, and MnCaP.

Polymer nanoparticle composite and composition for mri imaging including same

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ARTICLE; PHARMACEUTICAL BIOTECHNOLOGY Delivery of size-controlled long-circulating polymersomes in solid tumours, visualized by quantum dots and optical imaging in vivo

Evaluation of Lung Metastatic Tumor Using Dextran-DTPA-Mn Nanoprobes with Ultra-Short Echo-Time Imaging

Water-soluble hyperbranch polymer having paramagnetism

Polymer nanoparticle composite and composition for mri imaging including same