Robot Assisted Partial Nephrectomy (RAPN) is a standard of care for localized renal tumors. It allows a good carcinological control while limiting complications. Despite numerous benefits, the economic sustainability of robotic assistance remains a challenge in the French health care system.
View Article and Find Full Text PDFThe concept of drug targeting has resulted in a considerable variety of tools within nanotechnology, whose potentials in the special field of cancer are very interesting. There is a strong link between the structure and the surface of the vector on the one hand, and the biological target thus accessible on the other hand, as illustrated a number of typical examples. Parallel developments were made in the fields of therapy and diagnosis, stage by stage.
View Article and Find Full Text PDFEur J Pharm Biopharm
November 2011
We have designed an amphiphilic prodrug of the anticancer agent gemcitabine (dFdC), by covalent coupling to squalene. This bioconjugate, which self-assembled into nanoparticles (NPs) in water, was previously found to display an impressive anticancer activity both in vitro and in vivo. The present study aims to investigate the impact of SQdFdC nanoparticles on cellular membranes.
View Article and Find Full Text PDFThere are numerous anticancer agents based on a prodrug approach. However, no attempt has been made to review the ample available literature with a specific focus on the altered cell uptake pathways enabled by the conjugation and on the intracellular drug-release mechanisms. This article focuses on the cellular interactions of a broad selection of parenterally administered anticancer prodrugs based on synthetic polymers, proteins or lipids.
View Article and Find Full Text PDFHigh energy ball milling (HEBM) has been used for the first time to prepare PEGylated magnetite-silica (Fe(3)O(4)-SiO(2)) nanocomposites intended to be used for biological purposes. Surface amine groups were introduced by a silanization reaction involving 3-aminopropyl triethoxysilane (APTS) followed by PEGylation to yield long-term stable and stealth nanocomposites of 200nm in diameter. The efficient coverage by PEG chains was shown by isothermal titration calorimetry (ITC) where PEGylated nanocomposites did not interact with BSA compared to non-PEGylated counterparts which led to a significant change in enthalpy.
View Article and Find Full Text PDFNew nanotools for the imaging of cancer cells have been synthesized. Two-photon dye-doped 3-aminopropyltriethoxysilane-grafted mesoporous silica nanoparticles (MSN) have been grafted with folic acid (FA) functionalized PEG groups. Amine-PEG groups were first reacted with an activated ester derivative of FA.
View Article and Find Full Text PDFScientific advances have significantly improved the practice of medicine by providing objective and quantitative means for exploring the human body and disease states. These innovative technologies have already profoundly improved disease detection, imaging, treatment and patient follow-up. Today's analytical limits are at the nanoscale level (one-billionth of a meter) enabling a detailed exploration at the level of DNA, RNA, proteins and metabolites which are in fact nano-objects.
View Article and Find Full Text PDFWe have designed an amphiphilic prodrug of gemcitabine (dFdC) by its covalent coupling to a derivative of squalene, a natural lipid. The resulting bioconjugate self-assembled spontaneously in water as nanoparticles that displayed a promising in vivo anticancer activity. The aim of the present study was to provide further insight into the in vitro subcellular localization and on the metabolization pathway of the prodrug.
View Article and Find Full Text PDFNucleoside analogues are potent anticancer or antiviral agents that however display some limitations (rapid metabolism, induction of resistance). In order to overcome these drawbacks, we recently proposed new prodrugs, in which nucleoside analogues were covalently coupled to squalene (SQ). The resulting amphiphilic compounds spontaneously formed nanoparticles (NPs) and displayed a promising efficacy both in vitro and in vivo.
View Article and Find Full Text PDFMesoporous silica nanoparticles have unique properties: a specific large surface or a narrow casting of the sizes of pores. The perspectives of use are the creation of new tools for the premature diagnosis. For these potential biological applications, the harmlessness of these nanoparticles must be established.
View Article and Find Full Text PDFIn an earlier report, we demonstrated the superior anticancer efficacy of orally administered squalenoyl gemcitabine (SQdFdC) nanomedicine over its parent drug gemcitabine on rats bearing RNK-16 large granular lymphocytic (LGL) leukemia. In the present communication, we investigated the mechanisms behind this observation both at the cell and tissue level. The mechanisms were investigated by performing cytotoxicity, cell uptake, and biodistribution experiments.
View Article and Find Full Text PDFGemcitabine (2',2'-difluorodeoxyribofuranosylcytosine; dFdC) is an anticancer nucleoside analog active against wide variety of solid tumors. However, this compound is rapidly inactivated by enzymatic deamination and can also induce drug resistance. To overcome the above drawbacks, we recently designed a new squalenoyl nanomedicine of dFdC [4-N-trisnorsqualenoyl-gemcitabine (SQdFdC)] by covalently coupling gemcitabine with the 1,1',2-trisnorsqualenic acid; the resultant nanomedicine displayed impressively greater anticancer activity compared with the parent drug in an experimental murine model.
View Article and Find Full Text PDFThis study investigates 1) the anticancer efficacy of a new squalenoyl prodrug of gemcitabine (SQgem) in nanoassembly form compared with gemcitabine at equitoxic doses and 2) the subacute and acute preclinical toxicity of these compounds. The toxicity studies revealed that SQgem nanoassemblies, like gemcitabine, were toxic, and they led to dose-dependent mortality after daily i.v.
View Article and Find Full Text PDFUltrasmall superparamagnetic iron oxide (USPIO) particles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging. The coatings surrounding the USPIO inorganic core play a major role in both the in vitro stability and, over all, USPIO's in vivo fate. Different physicochemical properties such as final size, surface charge and coating density are key factors in this respect.
View Article and Find Full Text PDFGemcitabine is an anticancer nucleoside analogue active against various solid tumors. However, it possesses important drawbacks like a poor biological half-life and the induction of resistance. With the objective of overcoming the above drawbacks, we designed a new nanomedicine of gemcitabine and studied its anticancer efficacy against leukemia at preclinic.
View Article and Find Full Text PDFUltrasmall superparamagnetic iron oxide (USPIO) particles are efficient contrast agents used in vivo to enhance relaxation differences between healthy and pathological tissues. Detailed understanding of their physicochemical properties in suspension is necessary to guarantee the quality and safety of biological USPIO particles application. The ferrofluids stability against aggregation and gravitational settling affects their biodistribution and consequently the resulting contrast.
View Article and Find Full Text PDFNucleoside analogues display significant anticancer or antiviral activity by interfering with DNA synthesis. However, there are some serious restrictions to their use, including their rapid metabolism and the induction of resistance. We have discovered that the linkage of nucleoside analogues to squalene leads to amphiphilic molecules that self-organize in water as nanoassemblies of 100-300 nm, irrespective of the nucleoside analogue used.
View Article and Find Full Text PDFUltrasmall superparamagnetic iron oxide (USPIO) particles were structurally characterized in situ in an aqueous dilute suspension by energy dispersive X-ray diffraction (EDXD) and ex situ as powders obtained by lyophilization of the suspension by angular dispersive X-ray diffraction (ADXD) at 20 degrees C. Structural parameters obtained by the Rietveld method on ADXD data were used as starting parameters for modeling the structure of the particles in suspension. Although each particle is a single crystal, as evidenced by conventional X-ray diffraction, our results indicate that the structural order, specific to a crystal, does not extend to the entire volume of the particle.
View Article and Find Full Text PDFNew folate-conjugated superparamagnetic maghemite nanoparticles have been synthesized for the intracellular hyperthermia treatment of solid tumors. These ultradispersed nanosystems have been characterized for their physicochemical properties and tumor cell targeting ability, facilitated by surface modification with folic acid. Preliminary experiments of nanoparticles heating under the influence of an alternating magnetic field at 108 kHz have been also performed.
View Article and Find Full Text PDFIn recent years the fields of medicine and biology assist to an ever-growing innovation related to the development of nanotechnologies. In the pharmaceutical domain, for example, liposomes, polymer based micro and nanoparticles have been subjects of intense research and development during the last three decades. In this scenario metallic particles, which use was already suggested in the first half of the '80, are now experiencing a real renaissance.
View Article and Find Full Text PDFThe aim of this work was to develop a simple high-performance liquid chromatography (HPLC) technique with evaporative light scattering detection (ELSD) for the separation and quantification of the major phospholipid (PL) and lysophospholipid (LPL) classes contained in a pharmaceutical phospholipid-based emulsion. In the established method, phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyeline (SM), lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) were separated with a PVA-Sil stationary phase and a binary gradient from pure chloroform to methanol:water (94:6 v/v) at 3.4%/min.
View Article and Find Full Text PDFBackground/aims: Hepatocellular carcinoma (HCC) is known to be chemoresistant to anticancer drugs due to the multidrug resistant (MDR) transporters expression. Here, we compared in vitro and in vivo the anti-tumor efficacy of doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles (PIHCA-Dox) versus free doxorubicin (Dox). These nanoparticles are known to overcome the MDR phenotype.
View Article and Find Full Text PDFDespite extensive research in the field, the major problem in the ocular drug delivery domain still is rapid precorneal drug loss and poor corneal permeability. One of the approaches recently developed is the drug incorporation into cationic submicronic vectors which exploit the negative charges present at the corneal surface for increased residence time and penetration. This review will focus on the formulation of three main representative cationic colloids developed for ophthalmic delivery: liposomes, emulsions and nanoparticles (NP).
View Article and Find Full Text PDFThe tumor targeting properties of a new drug carrier synthesized by bioconjugation of folic acid (FA) to beta-cyclodextrins through a poly(ethylene glycol) (PEG) spacer (CD-PEG-FA) were investigated. Surface plasmon resonance demonstrated that CD-PEG-FA specifically interacts with immobilized folate binding protein (FBP) while the naked beta-cyclodextrins do not display any specific interaction. In vitro studies demonstrated that CD-PEG-FA was devoid of cell toxicity.
View Article and Find Full Text PDFThe present study is aimed to characterize the electrostatic parameters of oil in water emulsion droplets composed of MCT (medium chain triglycerides), PL (phospholipids) and Poloxamer and containing increasing concentrations of the cationic lipid oleylamine (OA), in Hepes 20 mM pH 7.4. The initial zeta-potential data suggesting saturation of the droplet surface at high OA concentrations were completed by supplementary analysis: the distribution of the oleylamine within the droplet was determined by reacting the amino groups with the hydrophilic TNBS (trinitrobenzenesulfonic acid), the method being initially standardised with vesicles.
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