Tailored Fabrication of 3D Nanopores Made of Dielectric Oxides for Multiple Nanoscale Applications.

Solid-state nanopores are a key platform for single-molecule detection and analysis that allow engineering of their properties by controlling size, shape, and chemical functionalization. However, approaches relying on polymers have limits for what concerns hardness, robustness, durability, and refractive index. Nanopores made of oxides with high dielectric constant would overcome such limits and have the potential to extend the suitability of solid-state nanopores toward optoelectronic technologies. Here, we present a versatile method to fabricate three-dimensional nanopores made of different dielectric oxides with convex, straight, and concave shapes and demonstrate their functionality in a series of technologies and applications such as ionic nanochannels, ionic current rectification, memristors, and DNA sensing. Our experimental data are supported by numerical simulations that showcase the effect of different shapes and oxide materials. This approach toward robust and tunable solid-state nanopores can be extended to other 3D shapes and a variety of dielectrics.

Increased endocytosis rate and enhanced lysosomal pathway of silica-coated superparamagnetic nanoparticles into M-HeLa cells compared with cultured primary motor neurons.

The unique properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable their use as magnetic biosensors, targeted drug delivery, magnetothermia, magnetic resonance imaging, etc. Today, SPIONs are the only type of metal oxide nanoparticles approved for biomedical application. In this work, we analyzed the cellular response to the previously reported luminescent silica coated SPIONs of the two cell types: M-HeLa cells and primary motor neuron culture. Both internalization pathways and intracellular fate of SPIONs have been compared for these cell lines using fluorescence and transmission electron microscopy. We also applied a pharmacological approach to analyze the endocytosis pathways of SPIONs into the investigated cell lines. The penetration of SPIONs into M-HeLa cells is already noticeable within 30 s of incubation through both caveolin-dependent endocytosis and micropinocytosis. However, incubation for a longer time (1 h at least) is required for the internalization of SPIONs into motor neuron culture cells provided by dynamin-dependent endocytosis and macropinocytosis. The intracellular colocalization assay reveals that the lysosomal internalization pathway of SPIONs is also dependent on the cell type. The lysosomal pathway is much more pronounced for M-HeLa cells compared with motor neurons. The emphasized differences in cellular responses of the two cell lines open up new opportunities in the application of SPIONs in the diagnostics and therapy of cancer cells.

Linkage of the Dinuclear Gold(I) Complex Luminescence and Origin of Endocyclic Amino Group of Cyclic P2N2-Bridging Ligands.

Gold(I) complexes of LAu2Cl2 composition based on P2N2 ligands, namely 1,5-diaza-3,7-diphosphacyclooctanes, containing ethylpyridyl substituents at the phosphorus atoms and sp2- or sp3-hybridized endocyclic nitrogen atoms were synthesized. The SCXRD analysis indicated the strong impact of the geometry of the nitrogen atom on the structure and conformational flexibility of the complexes. The N-aryl substituted ligand with the planar endocyclic nitrogen atom provides higher flexibility of the complex and an ability to bind the solvent molecules in the "host-guest" mode, whereas that kind of behavior is forbidden for the complex with an N-alkyl substituted ligand with a pyramidal nitrogen atom. The substituents at nitrogen atoms also control the origin of the emission, which is phosphorescence for the N-aryl substituted complex and fluorescence for the N-alkylaryl substituted complex. The phosphorescent gold(I) complex displays high cytotoxicity without selectivity toward the m-HeLa and normal cells, but the core-shell nanoparticles formed on the base of the complex demonstrate reduced cytotoxicity. The luminescence of the NPs allows tracking the complexes in the cell samples.

Emergence of Nanoscale Drug Carriers through Supramolecular Self-Assembly of RNA with Calixarene.

Supramolecular self-assembly is a powerful tool for the development of polymolecular assemblies that can form the basis of useful nanomaterials. Given the increasing popularity of RNA therapy, the extension of this concept of self-assembly to RNA is limited. Herein, a simple method for the creation of nanosized particles through the supramolecular self-assembly of RNA with a three-dimensional macrocycle from the calixarene family was reported for the first time. This self-assembly into nanoparticles was realized using cooperative supramolecular interactions under mild conditions. The obtained nanoparticles are able to bind various hydrophobic (quercetin, oleic acid) and hydrophilic (doxorubicin) drugs, as a result of which their cytotoxic properties are enhanced. This work demonstrates that intermolecular interactions between flexible RNA and rigid calixarene is a promising route to bottom-up assembly of novel supramolecular soft matter, expanding the design possibilities of nanoscale drug carriers.

Synthesis and Anticancer Evaluation of Novel 7-Aza-Coumarine-3-Carboxamides.

Herein, we report the design and synthesis of novel 7-aza-coumarine-3-carboxamides via scaffold-hopping strategy and evaluation of their in vitro anticancer activity. Additionally, the improved non-catalytic synthesis of 7-azacoumarin-3-carboxylic acid is reported, which features water as the reaction medium and provides a convenient alternative to the known methods. The anticancer activity of the most potent 7-aza-coumarine-3-carboxamides against the HuTu 80 cell line is equal to that of reference Doxorubicin, while the selectivity towards the normal cell line is 9-14 fold higher.

Antimicrobial and cytotoxic effects of ammonium derivatives of diterpenoids steviol and isosteviol.

Antimicrobial and cytotoxic activities of several ammonium derivatives of diterpenoids steviol and isosteviol have been investigated in vitro. The results have showed that these compounds possess high antibacterial activity against MRSA strains and cytotoxic effect against cancer cell lines MCF-7, M-HeLa, A-549, PC3, HepG2, T98G. Lead compounds 4 and 5 were detected, which, in the case of the MCF-7 cell line (human breast adenocarcinoma), showed IC50 at the doxorubicin level with a selectivity index of 5.0-5.2. Flow cytometry and laser confocal microscopy analysis demonstrated that the mechanism of cytotoxic effects of the tested compounds on MCF-7 cells could be associated with the induction of apoptosis along the mitochondrial pathway. At the same time, they did not cause hemolysis and showed only slight cytotoxicity with respect to normal human cells of embryonic lung (Wi-38). The obtained results allow us to consider the studied compounds as promising scaffolds for the design of new effective antibacterial drugs and anticancer agents targeting mitochondria.

Synthesis, antimicrobial activity and cytotoxicity of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues.

Four new triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues were synthesized by coupling with 8-bromoctyl- or 10- bromdecyltriphenylphosphonium bromide and evaluated for the in vitro antibacterial activity against S. aureus, B. cereus, E. faecalis, two MRSA strains isolated from patients and resistant to fluoroquinolone antibiotic ciprofloxacin and ß-lactam antibiotic amoxicillin, E. coli, antifungal activity against T. mentagrophytes C. albicans and cytotoxicity against human cancer cell lines M-HeLa, MCF-7, A549, HuTu-80, PC3, PANC-1 and normal cell line Wi-38. In these compounds a TPP cation was attached via an octyl or a decyl linker to the N 3 atom of the heterocycle moiety (thymine, 6-methyluracil, quinazoline-2,4-dione) which was bonded with 2',3',5'-tri- O - acetyl-greek beta-d-ribofuranose residue by the (1,2,3-triazol-4-il)methyl bridge. All synthesized compounds showed high antibacterial activity against S. aureus within the range of MIC values 1.2-4.3 greek muM, and three of them appeared to be bactericidal with respect to tis bacterium at MBC values 4.1-4.3 greek muM. Two lead compounds showed both high antibacterial activity against the MRSA strains resistant to Ciprofloxacin and Amoxicillin within the range of MIC values 1.0-4.3 greek muM and high cytotoxicity against human cancer cell lines HuTu-80 and MCF-7 within the range of IC50 values 6.4-10.2 greek muM. This is one of the few examples when phosphonium salts exhibited both antibacterial activity and cytotoxicity against human cancer cell lines. According to the results obtained the bactericidal effect of the lead compounds, unlike classical surfactants, was not caused by a violation of the integrity of the cytoplasmic membrane of bacteria and their cytotoxic activity is most likely associated both with the induction of apoptosis along the mitochondrial pathway and the arrest of the cell cycle in the G0/G1 phase.

Polymer-Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer.

The solution behavior and physicochemical characteristics of polymer-colloid complexes based on cationic imidazolium amphiphile with a dodecyl tail (IA-12) and polyacrylic acid (PAA) or DNA decamer (oligonucleotide) were evaluated using tensiometry, conductometry, dynamic and electrophoretic light scattering and fluorescent spectroscopy and microscopy. It has been established that PAA addition to the surfactant system resulted in a ca. 200-fold decrease in the aggregation threshold of IA-12, with the hydrodynamic diameter of complexes ranging within 100-150 nm. Electrostatic forces are assumed to be the main driving force in the formation of IA-12/PAA complexes. Factors influencing the efficacy of the complexation of IA-12 with oligonucleotide were determined. The nonconventional mode of binding with the involvement of hydrophobic interactions and the intercalation mechanism is probably responsible for the IA-12/oligonucleotide complexation, and a minor contribution of electrostatic forces occurred. The latter was supported by zeta potential measurements and the gel electrophoresis technique, which demonstrated the low degree of charge neutralization of the complexes. Importantly, cellular uptake of the IA-12/oligonucleotide complex was confirmed by fluorescence microscopy and flow cytometry data on the example of M-HeLa cells. While single IA-12 samples exhibit roughly similar cytotoxicity, IA-12-oligonucleotide complexes show a selective effect toward M-HeLa cells (IC50 1.1 µM) compared to Chang liver cells (IC50 23.1 µM).

Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action.

Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1-2 µM) and fungi Tm and Ca, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M-Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent apoptosis.

Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential.

Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide units, and calix[4]resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle-metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle-metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle-metallosurfactant system for the design of therapeutic cisplatin compositions.

N-Methyl-d-glucamine-Calix[4]resorcinarene Conjugates: Self-Assembly and Biological Properties.

Deep insight of the toxicity of supramolecular systems based on macrocycles is of fundamental interest because of their importance in biomedical applications. What seems to be most interesting in this perspective is the development of the macrocyclic compounds with biocompatible fragments. Here, calix[4]resorcinarene derivatives containing N-methyl- d-glucamine moieties at the upper rim and different chemical groups at the lower rim were synthesized and investigated. These macrocycles showed a tendency to self-aggregate in aqueous solution, and their self-assembly abilities depend on the structure of the lower rim. The in vitro cytotoxic and antimicrobial activity of the calix[4]resorcinarenes revealed the relationship of biological properties with the ability to aggregate. Compared to macrocycles with methyl groups on the lower rim, calix[4]resorcinarenes with sulfonate groups appear to possess very similar antibacterial properties, but over six times less hemolytic activity. In some ways, this is the first example that reveals the dependence of the observed hemolytic and antibacterial activity on the lipophilicity of the calix[4]arene structure.

Drug Binding and Delivery with Supramolecular System Based on Sodium Carboxymethylcellulose and Viologen Calix[4]resorcinol.

In the present work, a simple supramolecular approach was used to spontaneously form nanoparticles from sodium carboxymethylcellulose and viologen calix[4]resorcinol as a result of joint self-assembly in water at room temperature. Supramolecular interactions between them led to the formation of nanoparticles, the morphology and properties of which depend on polymer/macrocycle ratio. When there is excess of macrocycle, the nanoparticles bind lipophilic oleic acid, and when there is excess of polymer, they bind hydrophilic doxorubicin. Interestingly, the solubilization of lipophilic quercetin into these nanoparticles was significantly increased compared to the pure polymer and macrocycle, regardless of their ratio. The nanoparticles of triple composition (polymer/macrocycle/drug) have a more effective penetration ability into these cells than those of double composition (polymer/drug). The presented results are the first step towards the creation of new nanotechnologies to improve the bioavailability and delivery of bioactive components.

Laser-Induced Chirality of Plasmonic Nanoparticles Embedded in Porous Matrix.

Chiral plasmonic nanostructures have emerged as promising objects for numerous applications in nanophotonics, optoelectronics, biosensing, chemistry, and pharmacy. Here, we propose a novel method to induce strong chirality in achiral ensembles of gold nanoparticles via irradiation with circularly-polarized light of a picosecond Nd:YAG laser. Embedding of gold nanoparticles into a nanoporous silicate matrix leads to the formation of a racemic mixture of metal nanoparticles of different chirality that is enhanced by highly asymmetric dielectric environment of the nanoporous matrix. Then, illumination with intense circularly-polarized light selectively modifies the particles with the chirality defined by the handedness of the laser light, while their "enantiomers" survive the laser action almost unaffected. This novel modification of the spectral hole burning technique leads to the formation of an ensemble of plasmonic metal nanoparticles that demonstrates circular dichroism up to 100 mdeg. An unforeseen peculiarity of the chiral nanostructures obtained in this way is that 2D and 3D nanostructures contribute almost equally to the observed circular dichroism signals. Thus, the circular dichroism is neither even nor odd under reversal of direction of light propagation. These findings will help guide the development of a passive optical modulator and nanoplatform for enhanced chiral sensing and catalysis.

Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylAmino)(Phenyl) Phosphonium halides (APPs) containing one, two, or three diethylamino groups was obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions (20 °C) and high yields (93-98%). The structure of APP was established by NMR and XRD. A high in vitro cytotoxicity of APPs against M-HeLa, HuTu 80, PC3, DU-145, PANC-1, and MCF-7 lines was found. The selectivity index is in the range of 0.06-4.0 µM (SI 17-277) for the most active APPs. The effect of APPs on cancer cells is characterized by hyperproduction of ROS and depolarization of the mitochondrial membrane. APPs induce apoptosis, proceeding along the mitochondrial pathway. Incorporation of APPs into lipid systems (liposomes and solid lipid nanoparticles) improves cytotoxicity toward tumor cells and decrease toxicity against normal cell lines. The IC50s of lipid systems are lower than for the reference drug DOX, with a high SI (30-56) toward MCF-7 and DU-145. APPs exhibit high selective activity against Gram-positive bacteria S. aureus 209P and B. segeus 8035, including methicillin-resistant S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead APP.

Self-Assembling Metallocomplexes of the Amphiphilic 1,4-Diazabicyclo[2.2.2]octane Derivative as a Platform for the Development of Nonplatinum Anticancer Drugs.

New 1-cetyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide complexes with copper(II) bromide and lanthanum(III) nitrate were characterized using dynamic light scattering and transmission electron microscopy, with self-assembly and the morphological behavior elucidated. For the lanthanum(III) nitrate complex, the 3D crystal structure was characterized using X-ray diffractometry. These metallosurfactants were tested as antitumor agents, and a high cytotoxic effect comparable with doxorubicin was revealed against the M-HeLa and A-549 cell lines. Both complexes were 2 times more active toward the MCF-7 cell line than the breast cancer drug tamoxifen. The cytotoxic mechanism of complexes is assumed to be related to the induction of apoptosis through the mitochondrial pathway.

Mitochondria-targeted mesoporous silica nanoparticles noncovalently modified with triphenylphosphonium cation: Physicochemical characteristics, cytotoxicity and intracellular uptake.

Novel nanocomposite system based on mesoporous silica nanoparticles (MSNs) noncovalently modified with hexadecyltriphenylphosphonium bromide (HTPPB) has been prepared, thoroughly characterized and used for encapsulation of model cargo Rhodamine B (RhB). The high encapsulation efficacy of this dye by HTPPB-modified mesoporous particles was demonstrated by spectrophotometry and thermography techniques. The bioavailability of MSN@HTPPB was testified. Cytotoxicity assay revealed that a marked suppression of M-HeLa cancer cells (epithelioid carcinoma of the cervix) occurs at concentration of 0.06 µg/mL, while the higher viability of Chang liver normal cell line was preserved in the concentration range of 0.98-0.06 µg/mL. Hemolysis assay demonstrated that only 2% of red blood cells are destructed at ~ 30 µg/mL concentration. This allows us to select the most harmless compositions based on MSN@HTPPB with minimal side effects toward normal cells and recommend them for the development of antitumor formulations. Fluorescence microscopy technique testified satisfactory penetration of HTPPB-modified carriers into M-HeLa cells. Importantly, modification of the MSN with HTPPB is shown to promote efficient delivery to mitochondria. To the best of our knowledge, it is one of the first successful examples of noncovalent surface modification of the MSNs with lipophilic phosphonium cation that improves targeted delivery of loads to mitochondria.

Bis(α-hydroxycycloalkyl)phosphine Oxides Obtained from White Phosphorus via Phosphine Oxide H3 PO: Synthesis, Molecular Structure, Coordination Properties and Biological Activity.

Reaction of the electrochemically in situ from elemental white phosphorus generated phosphine oxide H3 PO in a single electrochemical cell, supplied with lead cathode and aluminium anode, with cyclic ketones (cyclopentanone and cyclohexanone) results in formation of secondary phosphine oxides (bis(α-hydroxycyclopentyl)phosphine oxide 2 a, isolated yield 15 %, and bis(α-hydroxycyclohexyl)phosphine oxide 2 b, isolated yield 12 %) with two α-hydroxycycloalkyl substituents at the phosphorus atom. Bis(α-hydroxycyclopentyl)phosphine oxide reacts with [PdCl2 (COD)] (COD=1,5-cyclooctadiene) to give a new palladium complex trans-[PdCl2 {P(OH)(cyclo-C5 H8 -1-OH)2 }2 ] (3 a, isolated yield 11 %) bearing phosphinous acid as a ligand formed via tautomerization of the phosphine oxide. Finally, the cytotoxicity of the synthesized secondary phosphine oxides on tumor and healthy human cell lines was studied. It was found that at a concentration of 10-6 -10-4  M, phosphine oxides 2 a,b exhibit similar IC50 values for the M-Hela cell line (ca. 50 mM), but are non-toxic for MCF-7 cells. For human alveolar adenocarcinoma cells (A-549), only 2 a is active (ca. 35 mM), while 2 b is not toxic.

Impact of oppositely charged shell and cores on interaction of core-shell colloids with differently charged proteins as a route for tuning of the colloids cytotoxicity.

The present work represents interactions between the core-shell nanoparticles and different proteins, exemplified by lysozyme (LSZ), pepsin, bovine serum albumin (BSA), thioredoxin (TRX) and yellow fluorescent protein (YFP). The core-shell morphology derives from the non-covalent deposition of polyethyleneimine (PEI) onto nanoprecipitated luminescent complex (AuCl)2L (L is cyclic PNNP ligand). Analysis of the data obtained by DLS, CD spectroscopy, luminescence derived from both (AuCl)2L and YFP reveal the electrostatically driven interaction of negatively charged proteins with the shell of PEI-(AuCl)2L. The fluorescence of YFP enables to reveal the inclusion of the protein molecules into the shell. The lack of any luminescent response of PEI-(AuCl)2L on TRX conforms its electrostatically driven interactions with the shell which, in turn, excludes a binding of the exposed thiol moieties with (AuCl)2L. The negatively charged surface of pepsin provides the greatest recharging of the PEI-based shell versus the other proteins, which is followed by the enhanced luminescence of (AuCl)2L. The significant effect of PEI-(AuCl)2L on the CD spectra of LSZ followed by the decreased intensity of (AuCl)2L-based luminescence points to specific interaction mode of PEI-(AuCl)2L with LSZ. The flow cytometry and fluorescent microscopy measurements revealed efficient internalization of PEI-(AuCl)2L into the Wi-38 cell samples resulting in the efficient staining of all cell organelles. The concentration dependent cytotoxicity of PEI-(AuCl)2L is detectably enhanced by LSZ, which is correlated with its interaction mode with the nanoparticles.

Terbium(III)-thiacalix[4]arene nanosensor for highly sensitive intracellular monitoring of temperature changes within the 303-313 K range.

The work introduces hydrophilic PSS-[Tb2(TCAn)2] nanoparticles to be applied as highly sensitive intracellular temperature nanosensors. The nanoparticles are synthesized by solvent-induced nanoprecipitation of [Tb2(TCAn)2] complexes (TCAn - thiacalix[4]arenes bearing different upper-rim substituents: unsubstituted TCA1, tert-buthyl-substituted TCA2, di- and tetra-brominated TCA3 and TCA4) with the use of polystyrenesulfonate (PSS) as stabilizer. The temperature responsive luminescence behavior of PSS-[Tb2(TCAn)2] within 293-333 K range in water is modulated by reversible changes derived from the back energy transfer from metal to ligand (M* → T1) correlating with the energy gap between the triplet levels of ligands and resonant 5D4 level of Tb3+ ion. The lowering of the triplet level (T1) energies going from TCA1 and TCA2 to their brominated counterparts TCA3 and TCA4 facilitates the back energy transfer. The highest ever reported temperature sensitivity for intracellular temperature nanosensors is obtained for PSS-[Tb2(TCA4)2] (SI = 5.25% K-1), while PSS-[Tb2(TCA3)2] is characterized by a moderate one (SI = 2.96% K-1). The insignificant release of toxic Tb3+ ions from PSS-[Tb2(TCAn)2] within heating/cooling cycle and the low cytotoxicity of the colloids point to their applicability in intracellular temperature monitoring. The cell internalization of PSS-[Tb2(TCAn)2] (n = 3, 4) marks the cell cytoplasm by green Tb3+-luminescence, which exhibits detectable quenching when the cell samples are heated from 303 to 313 K. The colloids hold unprecedented potential for in vivo intracellular monitoring of temperature changes induced by hyperthermia or pathological processes in narrow range of physiological temperatures.