In quest of a systematic framework for unifying and defining nanoscience

This article proposes a systematic framework for unifying and defining nanoscience based on historic first principles and step logic that led to a “central paradigm” (i.e., unifying framework) for traditional elemental/small-molecule chemistry. As such, a Nanomaterials classification roadmap is proposed, which divides all nanomatter into Category I: discrete, well-defined and Category II: statistical, undefined nanoparticles. We consider only Category I, well-defined nanoparticles which are >90% monodisperse as a function of Critical Nanoscale Design Parameters (CNDPs) defined according to: (a) size, (b) shape, (c) surface chemistry, (d) flexibility, and (e) elemental composition. Classified as either hard (H) (i.e., inorganic-based) or soft (S) (i.e., organic-based) categories, these nanoparticles were found to manifest pervasive atom mimicry features that included: (1) a dominance of zero-dimensional (0D) core–shell nanoarchitectures, (2) the ability to self-assemble or chemically bond as discrete, quantized nanounits, and (3) exhibited well-defined nanoscale valencies and stoichiometries reminiscent of atom-based elements. These discrete nanoparticle categories are referred to as hard or soft particle nanoelements. Many examples describing chemical bonding/assembly of these nanoelements have been reported in the literature. We refer to these hard:hard (H-n:H-n), soft:soft (S-n:S-n), or hard:soft (H-n:S-n) nanoelement combinations as nanocompounds. Due to their quantized features, many nanoelement and nanocompound categories are reported to exhibit well-defined nanoperiodic property patterns. These periodic property patterns are dependent on their quantized nanofeatures (CNDPs) and dramatically influence intrinsic physicochemical properties (i.e., melting points, reactivity/self-assembly, sterics, and nanoencapsulation), as well as important functional/performance properties (i.e., magnetic, photonic, electronic, and toxicologic properties). We propose this perspective as a modest first step toward more clearly defining synthetic nanochemistry as well as providing a systematic framework for unifying nanoscience. With further progress, one should anticipate the evolution of future nanoperiodic table(s) suitable for predicting important risk/benefit boundaries in the field of nanoscience

Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound

In the continuous search for cancer therapies with a higher therapeutic window, localized temperature-induced drug delivery may offer a minimal invasive treatment option. Here, a chemotherapeutic drug is encapsulated into a temperature-sensitive liposome (TSL) that is released at elevated temperatures, for example, when passing through a locally heated tumor. Consequently, high drug levels in the tumor tissue can be achieved, while reducing drug exposure to healthy tissue. Although the concept of temperature-triggered drug delivery was suggested more than thirty years ago, several chemical and technological challenges had to be addressed to advance this approach towards clinical translation. In particular, non-invasive focal heating of tissue in a controlled fashion remained a challenge. For the latter, high intensity focused ultrasound (HIFU) allows non-invasive heating to establish hyperthermia (40-45 degrees C) of tumor tissue over time. Magnetic resonance imaging (MRI) plays a pivotal role in this procedure thanks to its superb spatial resolution for soft tissue as well as the possibility to acquire 3D temperature information. Consequently, MRI systems emerged with an HIFU ultrasound transducer embedded in the patient bed (MR-HIFU), where the MRI is utilized for treatment planning, and to provide spatial and temperature feedback to the HIFU. For tumor treatment, the lesion is heated to 42 degrees C using HIFU. At this temperature, the drug-loaded TSLs release their payload in a quantitative fashion. The concept of temperature-triggered drug delivery has been extended to MR image-guided drug delivery by the co-encapsulation of a paramagnetic MRI contrast agent in the lumen of TSLs. This review will give an overview of recent developments in temperature-induced drug delivery using HIFU under MRI guidance

Novel lipidomimetic compounds and uses thereof

\u3cp\u3eDisclosed are lipidomimetic compounds of formula I (I) wherein: G represents a group satisfying formula II: HO-CH2-{CH(OH)-CH2-0}m-CH2-{C(=0)-0-CH2})q- formula II each n independently is an integer from 1-30; m is an integer from 1-10; q is 0 or 1. These compounds can be added to the lipid bilayer of thermosensitive liposomes, for the purpose of aiding in the prevention of leakage of the liposomes' contents at 37 DEG C., and retarding clearance from circulation.\u3c/p\u3

Novel lipidomimetic compounds and uses thereof

\u3cp\u3eDisclosed are lipidomimetic compounds of formula I (I) wherein: G represents a group satisfying formula II: HO-CH2-{CH(OH)-CH2-0}m-CH2-{C(=0)-0-CH2}q- formula II each n independently is an integer from 1-30; m is an integer from 1-10; q is 0 or 1. These compounds can be added to the lipid bilayer of thermosensitive liposomes, for the purpose of aiding in the prevention of leakage of the liposomes' contents at 37°C, and retarding clearance from circulation.\u3c/p\u3

Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance

Local drug delivery of doxorubicin holds promise to improve the therapeutic efficacy and to reduce toxicity profiles. Here, we investigated the release of doxorubicin and [Gd(HPDO3A)(H2O)] from different temperature-sensitive liposomes for applications in temperature-induced drug delivery under magnetic resonance image guidance. In particular, two temperature-sensitive systems composed of DPPC:MPPC:DPPE-PEG2000 (low temperature-sensitive liposomes, LTSL) and DPPC:HSPC:cholesterol:DPPE-PEG2000 (traditional temperature-sensitive liposomes, TTSL) were investigated. The co-encapsulation of [Gd(HPDO3A)(H2O)], a clinically approved MRI contrast agent, did not influence the encapsulation and release of doxorubicin. The LTSL system showed a higher leakage of doxorubicin at 37 °C, but a faster release of doxorubicin at 42 °C compared to the TTSL system. Furthermore, the rapid release of both doxorubicin and the MRI contrast agent from the liposomes occurred near the melting phase transition temperature, making it possible to image the release of doxorubicin using MRI

Dendrimers and magnetic resonance imaging

The multivalent character of dendrimers has positioned these well-defined, highly branched macromolecules at the forefront in the development of new contrast agents for biomedical magnetic resonance imaging (MRI). By modifying the periphery of the dendrimer with gadolinium(III) chelates, the relaxivity of the resulting MRI contrast agent is increased considerably, compared to low molecular weight Gd(III) chelates. The monodisperse character of dendrimers creates a unique opportunity to introduce dendritic MRI contrast agents into clinics. In addition, a prolonged vascular retention time is obtained due to the larger size of the dendritic molecules. By using dendrimers as multivalent scaffolds carrying multiple ligands, the interaction between ligand and marker can be enhanced through multivalent interactions. Current research focuses on the combination of multivalent targeting and enhanced relaxivity. This paper describes the application of dendrimers in biomedical MRI

Paramagnetic liposomes for molecular MRI and MRI-guided drug delivery

Liposomes are a versatile class of nanoparticles with tunable properties, and multiple liposomal drug formulations have been clinically approved for cancer treatment. In recent years, an extensive library of gadolinium (Gd)-containing liposomal MRI contrast agents has been developed for molecular and cellular imaging of disease-specific markers and for image-guided drug delivery. This review discusses the advances in the development and novel applications of paramagnetic liposomes in molecular and cellular imaging, and in image-guided drug delivery. A high targeting specificity has been achieved in vitro using ligand-conjugated paramagnetic liposomes. On targeting of internalizing cell receptors, the effective longitudinal relaxivity r1 of paramagnetic liposomes is modulated by compartmentalization effects. This provides unique opportunities to monitor the biological fate of liposomes. In vivo contrast-enhanced MRI studies with nontargeted liposomes have shown the extravasation of liposomes in diseases associated with endothelial dysfunction, such as tumors and myocardial infarction. The in vivo use of targeted paramagnetic liposomes has facilitated the specific imaging of pathophysiological processes, such as angiogenesis and inflammation. Paramagnetic liposomes loaded with drugs have been utilized for therapeutic interventions. MR image-guided drug delivery using such liposomes allows the visualization and quantification of local drug delivery. Copyright (c) 2013 John Wiley & Sons, Ltd

Research Spotlight : Multifunctional liposomes for MRI and image-guided drug delivery

Liposomes are a class of nanovesicles that have been explored extensively in the biomedical arena for early diagnosis and treatment of disease. In recent years, several liposomal drug formulations have been clinically approved in oncology. In a modular approach, the properties of liposomes can be tailored for combined molecular MRI, therapy and image-guided delivery of therapeutic drugs. Over the last year, extensive research has been performed in the authors laboratory on paramagnetic liposomes as innovative imaging probes for the detection of specific molecular or cellular targets and image-guided drug delivery using multifunctional, temperature-sensitive liposomes. A number of key achievements by the authors group will be highlighted in this research spotlight. © 2014 Future Science Ltd

The thulium complex of 1,4,7,10-tetrakis {[N-(1H-imidazol-2-yl)-carbamoyl]methyl]-1,4,7,10-tetraazacyclododecane (dotami) as a paraCEST contrast agent

\u3cp\u3e1,4,7,10-Tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7, 10-tetraazacyclododecane (dotami), a tetra(1H-imidazol-2-yl) derivative of the well-studied octadentate 1,4,7,10-tetrakis[(carbamoyl)methyl]- 1,4,7,10-tetraazacyclododecane (dotam) ligand, was synthesized by reaction of 1,4,7,10-tetraazacyclododecane with N-(1H-imidazol-2-yl) chloroacetamide in high yield. Its tricationic thulium complex was isolated as a water-soluble chloride salt. The detection of the mildly acidic amide and amine protons by direct proton NMR in aqueous solution was unsuccessful, but such exchangeable protons could be detected via their chemical exchange-dependent saturation transfer (CEST) effect. The observed CEST effect was distinctly different from that found for respective dotam complexes and is, therefore, ascribed to exchangeable protons associated with the imidazole substituent.\u3c/p\u3

Chelating amphiphilic polymers

\u3cp\u3eDescribed are amphiphilic polymers that are provided with chelating moieties. The amphiphilic polymers are block copolymers comprising a hydrophilic block and a hydrophobic block, with the chelating moieties linked to the end-group of the hydrophilic block. The disclosed polymers are capable of self-assembly into structures such as micelles and polymersomes. With suitable metals present in the form of coordination complexes with 5 the chelating moieties, the chelating amphiphilic polymers of the invention are suitable for use in various imaging techniques requiring metal labeling, such as MRI (T 1/T 2 weighted contrast agents or CEST contrast agents) SPECT, PET or Spectral CT.\u3c/p\u3