Fundamentals of tri-block copolymer self-assembly in solutions, and its relation to nano-templating

The purpose of this thesis is to obtain a better understanding of the formation mechanism of mesoporous silica materials, such as SBA-15 that use block copolymers as templating agents. Despite the fact that these materials are now extensively synthesized, the fundamental role of the different synthesis variables has not been determined on the basis of a detailed physical chemical study. Such a synthesis typically starts with the formation of spherical micelles that are converted into long cylindrical micelles during silica hydrolysis and condensation. As a result, a silica matrix with hexagonally ordered mesopores is obtained, after removing the micelles by extraction or calcination. The interactions between the block copolymer and the various additives (silica, acids, salts, solvents) during the first steps of the synthesis in solution are believed to play an important role in the creation of these highly structured materials. Therefore, the emphasis of this thesis lays on providing fundamental information on the self-assembly process of the tri-block copolymer P123 (EO20PO70EO20), typically used in the synthesis of SBA-15, at conditions that mimic those of mesoporous materials synthesis as closely as possible.DelftChemTechApplied Science

Cryogenic transmission electron microscopy: the technique of choice for the characterization of polymeric nanocarriers

This letter is meant to make scientists aware of the proper application of transmission electron microscopy (TEM) for the assessment of polymeric self-assemblies. Cryogenic (cryo)-TEM should be the method of choice. Here, we show the difference in morphologies observed in the same sample when using cryo-TEM and when using TEM with drying, demonstrating the importance of choosing the proper method.RST/Applied Radiation & Isotope

Summary report MTAA14–NAMLS11

RST/Applied Radiation & Isotope

Potential of MRI in radiotherapy mediated by small conjugates and nanosystems

Radiation therapy has made tremendous progress in oncology over the last decades due to advances in engineering and physical sciences in combination with better biochemical, genetic and molecular understanding of this disease. Local delivery of optimal radiation dose to a tumor, while sparing healthy surrounding tissues, remains a great challenge, especially in the proximity of vital organs. Therefore, imaging plays a key role in tumor staging, accurate target volume delineation, assessment of individual radiation resistance and even personalized dose prescription. From this point of view, radiotherapy might be one of the few therapeutic modalities that relies entirely on high-resolution imaging. Magnetic resonance imaging (MRI) with its superior soft-tissue resolution is already used in radiotherapy treatment planning complementing conventional computed tomography (CT). Development of systems integrating MRI and linear accelerators opens possibilities for simultaneous imaging and therapy, which in turn, generates the need for imaging probeswith therapeutic components. In this review, we discuss the role of MRI in both external and internal radiotherapy focusing on the most important examples of contrast agents with combined therapeutic potential.BT/BiocatalysisRST/Applied Radiation & Isotope

A Critical Review of Alpha Radionuclide Therapy: How to Deal with Recoiling Daughters?

This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefly on the clinical successes of radionuclides emitting only one alpha particle, the main focus of this article lies on those alpha-emitting radionuclides with multiple alpha-emitting daughters in their decay chain. While having the advantage of longer half-lives, the recoiled daughters of radionuclides like 224Ra (radium), 223Ra, and 225Ac (actinium) can do significant damage to healthy tissue when not retained at the tumour site. Three different approaches to deal with this problem are discussed: encapsulation in a nano-carrier, fast uptake of the alpha emitting radionuclides in tumour cells, and local administration. Each approach has been shown to have its advantages and disadvantages, but when larger activities need to be used clinically, nano-carriers appear to be the most promising solution for reducing toxic effects, provided there is no accumulation in healthy tissue.RST/Radiation, Science and TechnologyApplied Science

Nanocarrier-Mediated Photochemotherapy and Photoradiotherapy

Photothermal therapy (PTT) and photodynamic therapy (PDT) both utilize light to induce a therapeutic effect. These therapies are rapidly gaining importance due to the noninvasiveness of light and the limited adverse effect associated with these treatments. However, most preclinical studies show that complete elimination of tumors is rarely observed. Combining PDT and PTT with chemotherapy or radiotherapy can improve the therapeutic outcome and simultaneously decrease side effects of these conventional treatments. Nanocarriers can help to facilitate such a combined treatment. Here, the most recent advancements in the field of photochemotherapy and photoradiotherapy, in which nanocarriers are employed, are reviewed.Accepted Author ManuscriptRST/Applied Radiation & Isotope

Gamma Radiation Induced Contraction of Alkyne Modified Polymer Hydrogels

Gamma radiation triggered secondary crosslinking of dextran hydrogels leads to macroscopic hydrogel contraction. The authors use stable polymer hydrogels, prepared through azide-alkyne crosslinking, containing surplus alkyne groups. γ-irradiation of these gels leads to more alkyne crosslinking, enabling controlled increase of crosslink density, which in turn leads to an increase of hydrogel stiffness and macroscopic hydrogel contraction. Gel contraction scales linearly with the applied radiation dose. The same mechanism is applied to achieve γ-radiation triggered release of the small molecule cargo, akin to wringing out a sponge. γ-irradiation of touching hydrogel objects leads to gel fusion and the formation of a self-supporting gel connection, demonstrating the reactivity of the excess alkyne groups. They envision applications in gel gluing and the construction of complex gel architectures, as well as in responsive materials for controlled release.ChemE/Advanced Soft MatterRST/Applied Radiation & Isotope

Radiation-chemical and optical properties of a radio-fluorogenic gel

The radiation-induced polymerization and fluorescence intensity of a radio-fluorogenic medium consisting of tertiary-butyl acrylate (TBA) with ca 100 ppm maleimido-pyrene (MPy) display a super-linear dependence on dose and a close to inverse square root dependence on dose rate over the range from 2 to 30 Gy/min. In contrast with the fluorescence, the clarity and optical absorption remain unchanged on irradiation up to at least 17% monomer conversion for which the medium is a rigid gel.RST/Radiation, Science and TechnologyApplied Science

Modelling of the ^177mLu/¹⁷⁷Lu radionuclide generator

In order to determine the potential of 177mLu/177Lu radionuclide generator in 177Lu production it is important to establish the technical needs that can lead to a clinically acceptable 177Lu product quality. In this work, a model that includes all the processes and the parameters affecting the performance of the 177mLu/177Lu radionuclide generator has been developed. The model has been based on the use of a ligand to complex 177mLu ions, followed by the separation of the freed 177Lu ions. The dissociation kinetics of the Lu-ligand complex has been found to be the most crucial aspect governing the specific activity and 177mLu content of the produced 177Lu. The dissociation rate constants lower than 1*10-11 s-1 would be required to lead to onsite 177Lu production with specific activity close to theoretical maximum of 4.1 TBq 177Lu/mg Lu and with 177mLu content of less than 0.01%. Lastly, the calculations suggest that more than one patient dose per week can be supplied for a period of up to 7 months on starting with the 177mLu produced using 3 g Lu2O3 target with 60% 176Lu enrichment. The requirements of the starting 177mLu activity production needs to be adapted depending on the required patient doses, and the technical specifications of the involved 177mLu-177Lu separation process.RST/Applied Radiation & IsotopesChemE/Catalysis Engineerin

Core–shell structured gold nanoparticles as carrier for ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator

Background: Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. β− emitters are frequently used in RNT due to the long tissue penetration depth of the β− particles. The dysprosium-166/holmium-166 (166Dy/166Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide 166Dy and the emission of high energy β− from the daughter nuclide 166Ho. However, the internal conversion occurring after β− decay from 166Dy to 166Ho could cause the release of about 72% of 166Ho when 166Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for 166Dy/166Ho in vivo generator such that the loss of the daughter nuclide 166Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core–shell structured gold nanoparticles (AuNPs) with 166Dy and studied the retention of both 166Dy and 166Ho under various conditions. Results: The 166Dy was co-reduced with gold and platinum precursor to form the 166DyAu@AuNPs and 166DyPtAuNPs. The 166Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of 166Dy and 166Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both 166Dy and 166Ho was retained. The results show that the incorporation of 166Dy in AuNPs can prevent the escape of 166Ho released due to internal conversion. Conclusion: We developed a chelator-free radiolabelling method for 166Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide 166Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.RST/Applied Radiation & Isotope