New Cysteine-Containing PEG-Glycerolipid Increases the Bloodstream Circulation Time of Upconverting Nanoparticles

Upconverting nanoparticles have unique spectral and photophysical properties that make them suitable for development of theranostics for imaging and treating large and deep-seated tumors. Nanoparticles based on NaYF4 crystals doped with lanthanides Yb3+ and Er3+ were obtained by the high-temperature decomposition of trifluoroacetates in oleic acid and 1-octadecene. Such particles have pronounced hydrophobic properties. Therefore, to obtain stable dispersions in aqueous media for the study of their properties in vivo and in vitro, the polyethylene glycol (PEG)-glycerolipids of various structures were obtained. To increase the circulation time of PEG-lipid coated nanoparticles in the bloodstream, long-chain substituents are needed to be attached to the glycerol backbone using ether bonds. To prevent nanoparticle aggregation, an L-cysteine-derived negatively charged carboxy group should be included in the lipid molecule

Upconversion nanoparticles with anti-Stokes luminescence as bioimaging agents

Lanthanide-based upconversion nanoparticles attach great attention in theranostics due to their unique physicochemical and optical properties. It is innovative platform possessing peculiar properties for luminescent imaging, temperature mapping, sensing, and therapy. In present work we demonstrate advantages of new luminescent agents based on upconversion nanoparticles and hydrophylic biocompatible polymer

Upconversion nanoparticles with anti-Stokes luminescence as bioimaging agents

Lanthanide-based upconversion nanoparticles attach great attention in theranostics due to their unique physicochemical and optical properties. It is innovative platform possessing peculiar properties for luminescent imaging, temperature mapping, sensing, and therapy. In present work we demonstrate advantages of new luminescent agents based on upconversion nanoparticles and hydrophylic biocompatible polymer

Anticancer Nanotherapeutics in Clinical Trials: The Work behind Clinical Translation of Nanomedicine

The ultimate goal of nanomedicine has always been the generation of translational technologies that can ameliorate current therapies. Cancer disease represented the primary target of nanotechnology applied to medicine, since its clinical management is characterized by very toxic therapeutics. In this effort, nanomedicine showed the potential to improve the targeting of different drugs by improving their pharmacokinetics properties and to provide the means to generate new concept of treatments based on physical treatments and biologics. In this review, we considered different platforms that reached the clinical trial investigation, providing an objective analysis about their physical and chemical properties and the working mechanism at the basis of their tumoritr opic properties. With this review, we aim to help other scientists in the field in conceiving their delivering platforms for clinical translation by providing solid examples of technologies that eventually were tested and sometimes approved for human therapy

Role of energy transfer in a nanoinitiator complex for upconversion-driven polymerization

Upconversion nanoparticle (UCNP)-driven polymerization attracts great attention due to the ability of near-infrared light to penetrate deeper into biological media and synthetic materials than ultraviolet or visible light. Despite significant progress, the limitation of near-infrared light-triggered polymerization is associated with a key element of the photocurable composition, a UCNP/photoinitiator complex or a nanoinitiator. To determine the impact of resonance energy transfer from UCNPs to photoinitiator (PI) and its effect on polymerization, we developed two different photocurable compositions consisting of the polyethylene glycol diacrylate (PEG-DA), ultraviolet- and blue-emitting NaYF4: Yb3+, Tm3+ UCNPs with hydrophobic surface combined with water-soluble or insoluble PI. We found that transfer energy in these nanoinitiators proceeds differently: in UCNP/water-soluble PI (lithium phenyl-2,4,6-trimethylbenzoylphosphinate or LAP), it occurs through the photon-mediated transfer while in UCNP/water-insoluble PI (2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone or Irgacure 369), it takes place via the non-radiative resonant energy transfer. The impact of these processes in homolytic decomposition of initiator is extremely important in terms of the precisely controlled fabrication of polymer structures. PEG-DA facilitates the affinity between hydrophilic and hydrophobic components of the photocurable composition, which provides UCNP-driven cross-linking of biopolymers such as methacrylated hyaluronic acid and gelatin. 3D structures were prototyped to demonstrate the one-step rapid procedure of nanoinitiator preparation and emphasize the control of the energy transfer in UCNP/PI complexes for further development of UCNP-driven polymerization

Biodistribution of x-ray iodinated contrast agent in nano-emulsions is controlled by the chemical nature of the oily core

In this study, we investigated the role of the chemical nature of the oil droplet core of nano-emulsions used as contrast agents for X-ray imaging on their pharmacokinetics and biodistribution. To this end, we formulated PEGylated nano-emulsions with two iodinated oils (i.e., iodinated monoglyceride and iodinated castor oil) and compared them with another iodinated nano-emulsion based on iodinated vitamin E. By using dynamic light scattering and transmission electron microscopy, the three iodinated nano-emulsions were found to exhibit comparable morphologies, size, and surface composition. Furthermore, they were shown to be endowed with very high iodine concentration, which leads to stronger X-ray attenuation properties as compared to the commercial iodinated nano-emulsion Fenestra VC. The three nano-emulsions were i.v. administered in mice and monitored by microcomputed tomography (micro-CT). They showed high contrast enhancement in blood with similar half-life around 6 h but very different accumulation sites. While iodinated monoglycerides exhibited low accumulation in liver and spleen, high accumulation in spleen was observed for iodinated castor oil and in liver for vitamin E. These data clearly highlighted the important role of the oil composition of the nano-emulsion core to obtain strong X-ray contrast enhancement in specific targets such as liver, spleen, or only blood. These differences in biodistribution were partly attributed to differences in the uptake of the nanodroplets by the macrophages in vitro. Another key feature of these nano-emulsions is their long half-elimination time (several weeks), which offers sufficient retention for micro-CT imaging. This work paves the way for the design of nanoparticulate contrast agents for X-ray imaging of selected organs

Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs