Core–shell particles made of calcium carbonate and coated with biocompatible polymers using the Layer-by-Layer technique can be considered as a unique drug-delivery platform that enables us to load different therapeutic compounds, exhibits a high biocompatibility, and can integrate several stimuli-responsive mechanisms for drug release. However, before implementation for diagnostic or therapeutic purposes, such core–shell particles require a comprehensive in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Positron emission tomography (PET) is an advanced imaging technique for the evaluation of in vivo biodistribution of drug carriers; nevertheless, an incorporation of positron emitters in these carriers is needed. Here, for the first time, we demonstrate the radiolabeling approaches of calcium carbonate core–shell particles with different sizes (CaCO3 micron-sized core–shell particles (MicCSPs) and CaCO3 submicron-sized core–shell particles (SubCSPs)) to precisely determine their in vivo biodistribution after intravenous administration in rats. For this, several methods of radiolabeling have been developed, where the positron emitter (68Ga) was incorporated into the particle’s core (co-precipitation approach) or onto the surface of the shell (either layer coating or adsorption approaches). According to the obtained data, radiochemical bounding and stability of 68Ga strongly depend on the used radiolabeling approach, and the co-precipitation method has shown the best radiochemical stability in human serum (96–98.5% for both types of core–shell particles). Finally, we demonstrate the size-dependent effect of core–shell particles’ distribution on the specific organ uptake, using a combination of imaging techniques, PET, and computerized tomography (CT), as well as radiometry of separate organs. Thus, our findings open up new perspectives of CaCO3-radiolabeled core–shell particles for their further implementation into clinical practice.
Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n-3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52 +/- 0.01) than in Muscovites (0.43 +/- 0.01; p less than 0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n-3 and lower n-6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n-3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.
Modified phosphatidylcholine and sphingomyelin containing an anthryl end group attached to one of the Fatty acyl chains were used as fluorescent probes in an investigation of the molecular organization of human high-density lipoproteins (HDL). Monolayer experiments and NMR measurements showed the anthryl-labeled lipids to mimic closely the corresponding host phospholipids, the fluorophores being located near to the terminal CH3 groups of the fatty acid residues. The above fluorescent phospholipid probes made it possible for the first time to study differentially the behaviour of phosphatidylcholine and sphingomyelin in HDL. The probes were shown to interact in a different way with the apoprotein tryptophans and to be non-randomly distributed at the surface of the globules. The probable sphingomyelin binding site of apolipoprotein A-I was defined. Evidence was obtained suggesting the existence in high-density lipoproteins of two slowly exchanging phospholipid pools : one strongly bound to apoproteins, and the other free or loosely bound.Fluorescence parameters characterizing the fluidity of H D L phospholipids and their interaction with the apoprotein tryptophans were found to correlate with the HDL cholesterol level. The possible significance of the obtained results for a better understanding of the relation of high-density lipoproteins to coronary heart diseases is discussed.Lipid-soluble fluorescent probes such as pyrene, diphenylhexatriene or anthroxyloxystearic acids have been used in the structural analysis of serum lipoproteins [I -51. However, since the molecular probes thus far employed are quite different from the host lipids, they strongly perturb the regions they are monitoring [6-81. Moreover, the foreign probes frequently do not reside selectively within definite areas of the lipoprotein globule but may partition between them to an extcnt that is difficult to define [4]. In order to obtain more reliable information from experiments using extrinsic fluorescent probes we attempted to apply modified phospholipids with an apolar fluorescent group attached to one of the fatty-acyl chains. In previous communications we described the synthesis of fluorescent analogues (probes I and 11) of pliosphatidylcholine and sphingomyelin representing the two main phospholipid classes of serum lipoproteins [9,10]. The synthesis of similar anthryl-labeled phosphatidylcholines has been described by Stoffel et al. [ll].Since the fluorescent probes I and I1 are identical to natural phosphatidylcholine and sphingomyelin with respect to their head-group structure and polarity, a faithful report is expected concerning the behaviour of these two phospholipids in biological membranes and lipoproteins.The aim of the present investigation is to study the behaviour of the two phospholipid fluorescent probes I and I1 in artificial membranes and to exploit these probes to obtain differential information about the inolecular organization of phosphatidylcholine and sphingomyelin in human serum high-density lipoproteins (HDL2 and HDL3...
Real-time temperature monitoring within biological objects is a key fundamental issue for understanding the heating process and performing remote-controlled release of bioactive compounds upon laser irradiation. The lack of accurate thermal control significantly limits the translation of optical laser techniques into nanomedicine. Here, we design and develop hybrid (complex) carriers based on multilayered capsules combined with nanodiamonds (NV centers) as nanothermometers and gold nanoparticles (Au NPs) as nanoheaters to estimate an effective laser-induced temperature rise required for capsule rupture and further release of cargo molecules outside and inside cancerous (B16-F10) cells. We integrate both elements (NV centers and Au NPs) in the capsule structure using two strategies: (i) loading inside the capsule’s cavity (CORE) and incorporating them inside the capsule’s wall (WALL). Theoretically and experimentally, we show the highest and lowest heat release from capsule samples (CORE or WALL) under laser irradiation depending on the Au NP arrangement within the capsule. Applying NV centers, we measure the local temperature of capsule rupture inside and outside the cells, which is determined to be 128 ± 1.12 °C. Finally, the developed hybrid containers can be used to perform the photoinduced release of cargo molecules with simultaneous real-time temperature monitoring inside the cells.
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