Diagnosis, surgical treatment, and management of borderline ovarian surface epithelial neoplasms: Report of 2 cases and review of literature

AbstractOvarian borderline surface epithelial neoplasms occur infrequently in the pediatric population. Preoperative diagnostic criteria include ultrasound and serum tumor markers with definitive diagnosis made on pathologic examinations intraoperatively. Treatment typically involves resection of the tumor with an emphasis on preserving fertility. Patients diagnosed with borderline tumors generally have a good prognosis; however the possibility of recurrence remains. Two cases of 15 year-old females with borderline ovarian tumors are presented that add to the current literature by highlighting the diagnosis, clinical management, and follow-up postoperatively

In Vivo Recognition of Human Vascular Endothelial Growth Factor by Molecularly Imprinted Polymers

One of the mechanisms responsible for cancer-induced increased blood supply in malignant neoplasms is the overexpression of vascular endothelial growth factor (VEGF). Several antibodies for VEGF targeting have been produced for both imaging and therapy. Molecularly imprinted polymer nanoparticles, nanoMIPs, however, offer significant advantages over antibodies, in particular in relation to improved stability, speed of design, cost and control over functionalization. In the present study, the successful production of nanoMIPs against human VEGF is reported for the first time. NanoMIPs were coupled with quantum dots (QDs) for cancer imaging. The composite nanoparticles exhibited specific homing toward human melanoma cell xenografts, overexpressing hVEGF, in zebrafish embryos. No evidence of this accumulation was observed in control organisms. These results indicate that nanoMIPs are promising materials which can be considered for advancing molecular oncological research, in particular when antibodies are less desirable due to their immunogenicity or long production time

Does size matter? Study of performance of pseudo-ELISAs based on molecularly imprinted polymer nanoparticles prepared for analytes of different sizes

The aim of this work is to evaluate whether the size of the analyte used as template for the synthesis of molecularly imprinted polymer nanoparticles (nanoMIPs) can affect their performance in pseudo-enzyme linked immunosorbent assays (pseudo-ELISAs). Successful demonstration of a nanoMIPs-based pseudo-ELISA for vancomycin (1449.3 g mol) was demonstrated earlier. In the present investigation, the following analytes were selected: horseradish peroxidase (HRP, 44 kDa), cytochrome C (Cyt C, 12 kDa) biotin (244.31 g mol) and melamine (126.12 g mol). NanoMIPs with a similar composition for all analytes were synthesised by persulfate-initiated polymerisation in water. In addition, core-shell nanoMIPs coated with polyethylene glycol (PEG) and imprinted for melamine were produced in organics and tested. The polymerisation of the nanoparticles was done using a solid-phase approach with the correspondent template immobilised on glass beads. The performance of the nanoMIPs used as replacement for antibodies in direct pseudo-ELISA (for the enzymes) and competitive pseudo-ELISA for the smaller analytes was investigated. For the competitive mode we rely on competition for the binding to the nanoparticles between free analyte and corresponding analyte-HRP conjugate. The results revealed that the best performances were obtained for nanoMIPs synthesised in aqueous media for the larger analytes. In addition, this approach was successful for biotin but completely failed for the smallest template melamine. This problem was solved using nanoMIP prepared by UV polymerisation in an organic media with a PEG shell. This study demonstrates that the preparation of nanoMIP by solid-phase approach can produce material with high affinity and potential to replace antibodies in ELISA tests for both large and small analytes. This makes this technology versatile and applicable to practically any target analyte and diagnostic field

Carboxyl-fentanyl detection using optical fibre grating-based sensors functionalised with molecularly imprinted nanoparticles

Butyrylfentanyl is a new designer drug reported with growing use and related deaths. Routine toxicological analyses of this novel synthetic opioid drug have not been established yet. This work reports a fibre optic sensor that measures carboxyl-fentanyl which is the major metabolite of butyrylfentanyl presented in blood, providing a promising tool for detecting butyrylfentanyl intoxication. A long period fibre grating (LPG) sensor array operating at phase-matching condition is deployed in combination with a state-of-the-art molecular imprinting technique. Nano-sized molecularly imprinted polymers (nanoMIPs) are synthesised via a solid-phase approach and coated on the surface of an LPG array. An LPG array consists of two parts: a detection and a reference LPG. The former is functionalised with nanoMIPs prior to the measurements, whilst the latter is used to take into account the temperature response of the detection LPG. The developed sensor exhibits a gradual response over increasing concentrations of carboxyl-fentanyl from 0 to 1000 ng/mL with a minimal detected concentration of 50 ng/mL, that corresponds to a wavelength shift of 1.20 ± 0.2 nm. The Langmuir adsorption isotherm is applied to fit the analytical data which reveal a binding constant of 2.03 μM-1. The developed sensor shows high selectivity in detecting carboxyl-fentanyl among other drugs and potential interferents including morphine, cocaine, glucose and albumin. It shows a certain degree of cross-response to fentanyl which shares the same binding sites as carboxyl-fentanyl and therefore can be potentially used to detect fentanyl

Polymeric nanoparticles for optical sensing

Nanotechnology is a powerful tool for use in diagnostic applications. For these purposes a variety of functional nanoparticles containing fluorescent labels, gold and quantum dots at their cores have been produced, with the aim of enhanced sensitivity and multiplexing capabilities. This work will review progress in the application of polymeric nanoparticles in optical diagnostics, both for in vitro and in vivo detection, together with a discussion of their biodistribution and biocompatibility

A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format.

Here we show that molecularly imprinted polymer nanoparticles, prepared in aqueous media by solid phase synthesis with immobilised L-thyroxine, glucosamine, fumonisin B2 or biotin as template, can demonstrate comparable or better performance to commercially produced antibodies in enzyme-linked competitive assays. Imprinted nanoparticles-based assays showed detection limits in the pM range and polymer-coated microplates are stable to storage at room temperature for at least 1 month. No response to analyte was detected in control experiments with nanoparticles imprinted with an unrelated template (trypsin) but prepared with the same polymer composition. The ease of preparation, high affinity of solid-phase synthesised imprinted nanoparticles and the lack of requirement for cold chain logistics make them an attractive alternative to traditional antibodies for use in immunoassays

Surface-modified multifunctional MIP nanoparticles

The synthesis of core–shell molecularly imprinted polymer nanoparticles (MIP NPs) has been performed using a novel solid-phase approach on immobilised templates. The same solid phase also acts as a protective functionality for high affinity binding sites during subsequent derivatisation/shell formation. This procedure allows for the rapid synthesis, controlled separation and purification of high-affinity materials, with each production cycle taking just 2 hours. The aim of this approach is to synthesise uniformly sized imprinted materials at the nanoscale which can be readily grafted with various polymers without affecting their affinity and specificity. For demonstration purposes we grafted anti-melamine MIP NPs with coatings which introduce the following surface characteristics: high polarity (PEG methacrylate); electro-activity (vinylferrocene); fluorescence (eosin acrylate); thiol groups (pentaerythritol tetrakis(3-mercaptopropionate)). The method has broad applicability and can be used to produce multifunctional imprinted nanoparticles with potential for further application in the biosensors, diagnostics and biomedical fields and as an alternative to natural receptors

Biomimetic Silica Nanoparticles Prepared by a Combination of Solid-Phase Imprinting and Ostwald Ripening.

Herein we describe the preparation of molecularly imprinted silica nanoparticles by Ostwald ripening in the presence of molecular templates immobilised on glass beads (the solid-phase). To achieve this, a seed material (12 nm diameter silica nanoparticles) was incubated in phosphate buffer in the presence of the solid-phase. Phosphate ions act as a catalyst in the ripening process which is driven by differences in surface energy between particles of different size, leading to the preferential growth of larger particles. Material deposited in the vicinity of template molecules results in the formation of sol-gel molecular imprints after around 2 hours. Selective washing and elution allows the higher affinity nanoparticles to be isolated. Unlike other strategies commonly used to prepare imprinted silica nanoparticles this approach is extremely simple in nature and can be performed under physiological conditions, making it suitable for imprinting whole proteins and other biomacromolecules in their native conformations. We have demonstrated the generic nature of this method by preparing imprinted silica nanoparticles against targets of varying molecular mass (melamine, vancomycin and trypsin). Binding to the imprinted particles was demonstrated in an immunoassay (ELISA) format in buffer and complex media (milk or blood plasma) with sub-nM detection ability