Albumin Molecule Research Articles

Single Protein Encapsulated Doxorubicin as an Efficacious Anticancer Therapeutic.

Small-molecule chemotherapeutics are potent and effective against a variety of malignancies, but common and severe side effects restrict their clinical applications. Nanomedicine approaches represent a major focus for improving chemotherapy, but have met limited success. To overcome the limitations of chemotherapy drugs, we have developed a novel Single Protein Encapsulation (SPE)-based drug formulation and delivery platform and tested its utility in improving doxorubicin (DOX) treatment. Using this methodology, a series of SPEDOX complexes were generated by encapsulating various numbers of DOX molecules into a single human serum albumin (HSA) molecule. UV/fluorescence spectroscopy, membrane dialysis, and dynamic light scattering techniques showed that SPEDOXs are stable and uniform as monomeric HSA and display unique properties distinct from those of DOX and DOX-HSA mixture. Furthermore, detailed procedures to precisely monitor and control both DOX payload and binding strength to HSA were established. Breast cancer xenograft tumor studies revealed that SPEDOX-6 treatment displays improved pharmacokinetic profiles, higher antitumor efficacy, and lower DOX accumulation in the heart tissue compared with unformulated DOX. This SPE technology, which does not involve nanoparticle assembly and modifications to either small-molecule drugs or HSA, may open up a new avenue for developing new drug delivery systems to improve anticancer therapeutics.

Multi Technique Investigation on Binding Interaction between 5-(2-Thiazolylazo)-2,4,6-Triaminopyrimidine and Hsa and Bsa

In research laboratories and various industries, azo compounds are among the most effective and commonly used organic dyes. Throughout this research the interaction between human and bovine serum albumins with 5-(2-Thiazolylazo)-2,4,6-Triaminopyrimidine (TTP) was explored using methods of spectroscopy and analysis of molecular modeling. The fluorescence quenching results revealed that static and dynamic processes are the quenching mechanisms for human and bovine serum albumins, respectively. The results of the quenching experiment were used to measure thermodynamic parameters [[EQUATION]] which showed that the binding process that takes place spontaneously and revealed that human and bovine serum albumins are very firmly binding through hydrogen bonds, van der Waals forces interactions and electrostatic forces. Calculations of Fӧrster energy transfer, synchronous fluorescence spectroscopy and docking analysis showed TTP bindings in short distances to the Trp residues of human and bovine serum albumin molecules. Docking study showed that TTP molecule has four hydrogen bonds with HSA, two hydrogen bonds with BSA and several hydrophobic contacts with human and bovine serum albumins. FT-IR results showed that serum albumins interact with TTP molecule primarily through hydrophobic and hydrophilic interactions, and that the secondary structure of serum albumins is modified.

CQDs/Au NPs Modified Polysulfone Membrane with Antibacterial Function and Photocatalytic Activity for Degradation of Methylene Blue

Herein, carbon quantum dots (CQDs) and gold nanoparticles (Au NPs) were synthesized and deposited on the surface of Polysulfone (PSF) membrane using polydopamine as the sublayer, resulting in excellent antibacterial property and photocatalytic activity for degradation of organic dyes. Water contact angle (WCA) of the membrane before and after surface modification dropped from [Formula: see text] to [Formula: see text], due to outstanding hydrophilicity of CQDs. The antibacterial test against [Formula: see text]. [Formula: see text] found that the CQDs/Au NPs were beneficial to improve the antibacterial property of the membrane, and the antibacterial rate could reach 90%, effectively prolonging the service life of the membrane. In addition, the adsorption of bovine serum albumin (BSA) molecules on the membrane was significantly reduced, and the irreversible fouling ratio also decreased from 41.3% to 10.7%. On the other hand, the CQDs/Au NPs layer was used as a photocatalytic material for degradation of methylene blue.

Determinants of Intraparenchymal Infusion Distributions: Modeling and Analyses of Human Glioblastoma Trials.

Intra-parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribution from clinical MR images. Computer-assisted planning has been proposed to mitigate risk for inadequate delivery through quantitative understanding of infusion characteristics. We present results from human studies and simulations of intratumoral infusions of immunotoxins in glioblastoma patients. Gd-DTPA and 124I-labeled human serum albumin (124I-HSA) were co-infused with the therapeutic, and their distributions measured in MRI and PET. Simulations were created by modeling tissue fluid mechanics and physiology and suggested that reduced distribution of tracer molecules within tumor is primarily related to elevated loss rates computed from DCE. PET-tracer on the other hand shows that the larger albumin molecule had longer but heterogeneous residence times within the tumor. We found over two orders of magnitude variation in distribution volumes for the same infusion volumes, with relative error ~20%, allowing understanding of even anomalous infusions. Modeling and measurement revealed that key determinants of flow include infusion-induced expansion and loss through compromised BBB. Opportunities are described to improve computer-assisted CED through iterative feedback between simulations and imaging.

Effect of methotrexate and its photodegradation products on the temperature induced denaturation of human serum albumin.

Effect of the photodegradation of chemotherapeutic agent methotrexate on the denaturation of human serum albumin has been studied by differential scanning calorimetry and fluorimetric measurements. Photoluminescence studies highlighted entropy driven binding of both methotrexate molecules and its degradation products to the albumin molecules. The calorimetric measurements evaluated by the Kissinger method show elevated activation energy in the presence of methotrexate. Similar but moderated enhancement of the activation energy was obtained in the presence of the photodegradation products of methotrexate. These results highlight stabilization of the human serum albumin by the methotrexate drug which finding may contribute to fine tuning of methotrexate applications in therapy.

Prediction of the interaction between HIV viruses and Human Serum Albumin (HSA) molecules using an equilibrium dynamics simulation program for application in bio medical science

Atomic interaction of Human Serum Albumin (HSA) protein and HIV virus is important in medical sciences. In the present study, for the first time, Molecular Dynamics (MD) simulation based on Newton's law used to predict the destruction of HSA structure by the HIV virus with atomic. In our research, each HSA and HIV molecules are simulated by As, C, Ca, Cl, N, O, and S atoms and contrived by DREIDING and Universal Force Fields to describe their atomic evolution. The atomic interaction between these structures described by calculating the total energy, center of mass distance, diffusion coefficient and volume of atomic structures. The calculated rates for these physical parameters show the attraction force between HSA protein and HIV virus, in which the COM distances of these structures varies from 7.7 Å to 3.62 Å after 1 ns. Structurally, the volume of HSA protein raises from 152,241 Å3 to 163,697Å3 after atomic interaction with the HIV virus which this atomic manner shows the protein destruction. Further, the simulation result show that the environmental parameters such as temperature is an important factor in HAS protein and HIV virus mutual interaction, by increasing the temperature of the atoms from 300 K to 350 K the attraction force between these structures increases and diffusion coefficient of HIV virus into HSA protein changes from 0.43 μm2/s to 0.35 μm2/s.

Improved delivery and antimetastatic effects of Stattic by self-assembled amphiphilic pendant-dendron copolymer micelles in breast cancer cell lines

Stattic is a signaling pathway inhibitor that could potentially impede the progression of tumor metastasis. However, the pharmaceutical applications of Stattic are hampered by its poor water solubility. In this study, we explored the integration of Stattic within amphiphilic pendant-dendron copolymeric (P71D3) micelles to improve its water solubility and delivery towards tumor cells. The P71D3/Stattic micelles with a 1:1.2 (P71D3:Stattic) ratio optimized for subsequent studies were 164 nm in diameter with a drug loading percentage of 52% w/w. These P71D3/Stattic micelles demonstrated a higher drug release (32%) in acidic tumor conditions compared to neutral physiological conditions (14%). However, rapid and high Stattic release was observed when dialyzed against a simulated plasma solution containing 4% albumin. Interestingly, when the same Stattic-loaded micelles and 4% albumin solution were in direct contact, the albumin molecules bound to the surface of the micelles, forming a protein corona. P71D3/Stattic micelles were found to be 30- to 90-fold more potent and to decrease the effective antimotility concentration by 3- to 6-fold compared to free Stattic in metastatic human and murine mammary cancer cells. The P71D3/Stattic micelles effectively enhanced the potency of the drug as determined from the in vitro studies, suggesting the use of P71D3/Stattic micelles as a promising antimetastatic agent worthy of further study.

Computational Fluid Dynamics (CFD) Modeling and Simulation of Flow Regulatory Mechanism in Artificial Kidney Using Finite Element Method.

There is an enormous need in the health welfare sector to manufacture inexpensive dialyzer membranes with minimum dialysis duration. In order to optimize the dialysis cost and time, an in-depth analysis of the effect of dialyzer design and process parameters on toxins (ranging from tiny to large size molecules) clearance rate is required. Mathematical analysis and enhanced computational power of computers can translate the transport phenomena occurring inside the dialyzer while minimizing the development cost. In this paper, the steady-state mass transport in blood and dialysate compartment and across the membrane is investigated with convection-diffusion equations and tortuous pore diffusion model (TPDM), respectively. The two-dimensional, axisymmetric CFD model was simulated by using a solver based on the finite element method (COMSOL Multiphysics 5.4). The effect of design and process parameters is analyzed by solving model equations for varying values of design and process parameters. It is found that by introducing tortuosity in the pore diffusion model, the clearance rate of small size molecules increases, but the clearance rate of large size molecules is reduced. When the fiber aspect ratio (db/L) varies from 900 to 2300, the clearance rate increases 37.71% of its initial value. The results also show that when the pore diameter increases from 10 nm to 20 nm, the clearance rate of urea and glucose also increases by 2.09% and 7.93%, respectively, with tolerated transport of albumin molecules.

Construction a Long-Circulating Delivery System of Liposomal Curcumin by Coating Albumin.

Although the bioavailability and stability of curcumin can be greatly improved by liposomes encapsulation, its application is still limited due to the short circulating time. In this present work, we aim to construct a long-circulating delivery system of liposomal curcumin (Cur-Lips) by coating bovine serum albumin (BSA), namely, BSA-coated liposomal curcumin (BSA-Cur-Lips). The effects of coating albumin on the physicochemical properties of Cur-Lips were investigated. It was found that BSA-Cur-Lips was more spherical, more homogeneous in size, and significantly larger than Cur-Lips. Combining sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Coomassie bright blue staining, and X-ray photoelectron spectroscopy analysis (XPS), we confirmed that albumin molecules were stably located on the surface of BSA-Cur-Lips. In addition, the impacts of the coating albumin on the Cur-Lips release and phagocytosis by mouse macrophages Raw264.7 in vitro were investigated. We found that no significant initial burst drug release effect was observed for both Cur-Lips and BSA-Cur-Lips and the presence of albumin can enhance the liposome structure stability and slow down the release of Cur. More importantly, the macrophage phagocytosis of Cur-Lips was significantly reduced after coating albumin. In conclusion, coating albumin is a promising approach for developing a long-circulating delivery system of liposomal curcumin, and its properties including low phagocytosis, slow drug release, enhanced stability, and nontoxicity give this system great prospects for practical use.

Far-red pentamethine cyanine dyes as fluorescent probes for the detection of serum albumins.

Benzothiazole based cyanine dyes with bridged groups in the pentamethine chain were studied as potential far-red fluorescent probes for protein detection. Spectral-luminescent properties were characterized for unbound dyes and in the presence of serum albumins (bovine (BSA), human (HSA), equine (ESA)), and globular proteins (β-lactoglobulin, ovalbumin). We have observed that the addition of albumins leads to a significant increase in dyes fluorescence intensity. However, the fluorescent response of dyes in the presence of other globular proteins was notably lower. The value of fluorescence quantum yield for dye bearing a sulfonate group complexed with HSA amounted to 42% compared with 0.2% for the free dye. The detection limit of HSA by this dye was greater than 0.004 mg ml−1 which indicates the high sensitivity of dye to low HSA concentrations. Modelling of structure of the dyes complexes with albumin molecules was performed by molecular docking. According to these data, dyes could bind to up to five sites on the HSA molecule; the most preferable are the haemin-binding site in subdomain IB and the dye-binding site in the pocket between subdomains IA, IIA and IIIA. This work confirms that pentamethine cyanine dyes could be proposed as powerful far-red fluorescent probes applicable for highly sensitive detection of albumins.

A Novel Near Infrared Spectroscopy Based Device for Albumin Estimation.

In this paper we have proposed a fluorescence based spectroscopy device which can be used to quantitatively estimate the amount of albumin that gets excreted out of our body. Albumin is a significant protein in bio-fluids and performs a wide range of metabolic functions. The dye that has been used as a fluorescent indicator for the presence of albumin in this study has been earlier tested with bovine serum albumin (BSA) and human serum albumin (HSA) with satisfactory results. The method is based on principle of fluorescence in near infrared range (NIR) of 700 to 850 nm by using a novel dye with the test mixture. The chosen near infrared range has a benefit of absence of the auto fluorescence of the bio-molecules present in urine other than the albumin molecules. The system consists of: light source, spectroscopic chamber, sensing and computational unit. The study shows the stability and reproducibility of device so as to avoid fluctuations of voltage and other undesirables. The optimization with bovine serum albumin and human serum albumin has been done and the device can sense as low as 100 nM concentration precisely and accurately.Clinical Relevance-The system being presented is intended for developing a low cost point of care testing device for determining albumin concentration in urine.

Correlation between assembly structure of a gamma irradiated albumin nanoparticle and its function as a drug delivery system

The present study correlates the structure of an albumin nanoparticle with its function as a drug delivery system. The albumin nanoparticle was created by a clean and size-controlled desolvation method in combination with gamma irradiation as a cross-linker. It is composed of 3950 albumin molecules with a molecular weight of 5.78E + 02 MDa and the binding between the albumin molecules creates new hydrophobic pockets. Our hypothesis was that the very assembly structure of the nanoparticle played a key role in making it a suitable drug delivery system. In order to study how the assembly of the nanoparticle enhanced its function as such, we used a hydrophobic drug, Emodin. The high affinity of the nanoparticle for the drug was studied with spectroscopy. We found that the nanoparticle’s many hydrophobic pockets improved the encapsulation efficiency of the system. In cell toxicity and haemolysis experiments, the nanoparticle’s toxicity levels were low. These results suggest that the nanoparticle has great potential as a drug delivery system.

Hot-pressed PAN/PVDF hybrid electrospun nanofiber membranes for ultrafiltration

The objective of this study was to develop highly efficient and cost-effective ultrafiltration (UF) media/membranes from electrospun nanofibers alone without using expensive/complicated chemical modification methods. The hypothesis was that, during hot-pressing hybrid electrospun nanofiber membranes (ENMs) consisting of a thermoplastic polymer (e.g., PVDF) and a skeleton polymer (e.g., PAN), the PVDF nanofibers could be partially melted/softened even broken, leading to the conglutination/fusion of nanofibers. This would further result in the reduction of membrane porosities and the variation of membrane morphologies/structures; consequently, the membrane equivalent/apparent pore sizes would also be decreased. To test the hypothesis, as-collected PAN/PVDF hybrid ENMs (PPHENMs) were hot-pressed at 180 °C (above the PVDF melting point of ~177 °C) by using different pressures of 2.5, 5, and 10 MPa; for comparison, PPHENMs were also prepared upon being hot-pressed at 60 °C. The PPHENMs180 hot-pressed under 10 MPa had the lowest porosity of ~16.7 vol%, indicating that nanofibers occupied ~5/6 vol in the membrane; and the membrane exhibited high pure water flux value of ~200 L m−2∙h−1 under the applied pressure of 4 bar. Moreover, this membrane could completely reject/remove polystyrene particles with sizes larger than 20 nm from water; and the rejection percentages for bovine serum albumin and bovine γ-globulin molecules reached ~60% and ~75%, respectively. Therefore, hot-pressed hybrid ENMs made of thermoplastic nanofibers and skeleton nanofibers could provide an innovative and facile approach for the development of high-performance UF media/membranes.

Differences in cryostimulation and sauna effects on post-exercise changes in blood serum of athletes

ObjectivesThere is a growing body of evidence supporting the role of whole-body cryostimulation (WBC) and sauna – bathing as treatments for relaxation, mental well-being and several health problems. Despite their polar opposite temperatures, both of these treatments come with a dose of similar health benefits. This study is designed to compare effects of WBC and sauna application on the athletes’ response to exercise. DesignThe blood samples were collected from 10 professional cross-country skiers at four stages: before exercise, after exercise, at 1-h recovery and after 24 h of rest in sessions before and after 10 thermal treatments. Differential scanning calorimetry (DSC) was used to examine the process of serum denaturation. The parameters of endothermic transition were compared at various stages of each exercise session. ResultsPost-exercise changes in DSC profiles of athlete's blood serum are similar in character but clearly stronger in the session held after sauna treatments and slightly weaker after WBC than those in the session not preceded by treatments. These changes can be, at least in part, explained by the exercise induced increase in the concentration of oxidized albumin. A return of serum denaturation transition to pre-exercise shape has been observed within a few hours of rest. It suggests relatively quick restoration of a fraction of non-oxidized albumin molecules during the recovery period. ConclusionsAn exercise performed by athletes after a series of sauna treatments leads to temporary greater modification of the blood serum proteome than the similar exercise during the session preceded by WBC treatments.

Protection against SIV in Rhesus Macaques Using Albumin and CD4-Based Vector-Mediated Gene Transfer

Antibody-like molecules were evaluated with potent simian immunodeficiency virus (SIV) neutralizing properties (immunoadhesins) that were delivered by a recombinant adeno-associated virus (rAAV) vector in the SIV-infected rhesus macaque model. When injected intramuscularly into the host, the vector directs in vivo production of the transgenes with antibody-like binding properties that lead to serum neutralizing activity against SIV. To extend the half-life of the immunoadhesins, rhesus cluster of differentiation 4 (CD4) and a single-chain antibody (4L6) were fused with albumin molecules, and these constructs were tested in our model of SIV infection. Antibody-based immunoadhesins provided high serum neutralizing titers against the original SIV strain. CD4-based immunoadhesins provided a wider spectrum of neutralization against different SIV strains in comparison to antibody-based therapeutics and had the potential to protect against high viral challenging doses. Although the albumin-antibody fusion immunoadhesin provided strong and prolonged protection of the immunized animals against SIV challenge, the albumin-CD4 fusion altered the specificity and decreased the overall protection effectiveness of the immunoadhesin in comparison to the antibody-based molecules. Albumin-based immunoadhesins increase in vivo longevity of the immune protection; however, they present challenges likely linked to the induction of anti-immunoadhesin antibodies.

Combination immunotherapy of αPD-1 and extended half-life IL-2 clears established GL261 gliomas in an MHC class I independent fashion

Abstract Glioblastoma multiforme (GBM) is a deadly CNS malignancy with an average survival of ~12 months post diagnosis despite aggressive treatment. Immunotherapy approaches to treat GBM are being developed, but the unique immune environment of the brain and the immunosuppressive features of GBM have complicated early efforts. Even αPD-1 checkpoint blockade, highly useful in the context of melanoma, has proved ineffective in the treatment of GBM. In order to promote the efficacy of αPD-1 against the GL261 murine model of GBM, we supplemented this therapy with an engineered IL-2 cytokine. IL-2 therapy has been used clinically for metastatic melanoma and renal cancer, but its short half-life in circulation necessitated dangerously high doses to keep the drug concentration sufficiently high. Fusing IL-2 to the mouse serum albumin molecule (MSA-IL-2), extends the cytokine’s half-life. While neither αPD-1 nor MSA-IL-2 are effective monotherapies against the GL261 model tumor, we have found this combination immunotherapy to provide durable tumor clearance and to create immunologic memory capable of resisting GL261 rechallenge. Most strikingly, this combination therapy is independent of the CD8 T cell function, clearing established GL261 tumors in mice incapable of MHC class I restricted antigen presentation. Independence of MHC class I restricted antigen presentation makes this combination immunotherapy using αPD-1 checkpoint blockade both highly novel and translatable to clinical use.

Grafting Thin Layered Graphene Oxide onto the Surface of Nonwoven/PVDF-PAA Composite Membrane for Efficient Dye and Macromolecule Separations.

This study investigates the permeance and rejection efficiencies of different dyes (Rhodamine B and methyl orange), folic acid and a protein (bovine serum albumin) using graphene oxide composite membrane. The ultrathin separation layer of graphene oxide (thickness of 380 nm) was successfully deposited onto porous polyvinylidene fluoride-polyacrylic acid intermediate layer on nonwoven support layer using vacuum filtration. The graphene oxide addition in the composite membrane caused an increased hydrophilicity and negative surface charge than those of the membrane without graphene oxide. In the filtration process using a graphene oxide composite membrane, the permeance values of pure water, dyes, folic acid and bovine serum albumin molecules were more severely decreased (by two orders of magnitude) than those of the nonwoven/polyvinylidene fluoride-polyacrylic acid composite membrane. However, the rejection efficiency of the graphene oxide composite was significantly improved in cationic Rhodamine B (from 9% to 80.3%) and anionic methyl orange (from 28.3% to 86.6%) feed solutions. The folic acid and bovine serum albumin were nearly completely rejected from solutions using either nonwoven/polyvinylidene fluoride-polyacrylic acid or nonwoven/polyvinylidene fluoride-polyacrylic acid/graphene oxide composite membrane, but the latter possessed anti-fouling property against the protein molecules. The separation mechanism in nonwoven/polyvinylidene fluoride-polyacrylic acid membrane includes the Donnan exclusion effect (for smaller-than-pore-size solutes) and sieving mechanism (for larger solutes). The sieving mechanism governs the filtration behavior in the nonwoven/polyvinylidene fluoride-polyacrylic acid/graphene oxide composite membrane.

Rational Design of "Three-in-One" Ratiometric Nanoprobes: Protein-Caged Dityrosine, CdS Quantum Dots, and Gold Nanoclusters.

Recently, multiplexed ratiometric fluorescence sensors for detecting several analytes have received much interest because of their multifunctionality. Here, we fabricate a novel trinity fluorescent nanoprobe in which one small-molecule fluorophore, blue-emissive dityrosine (diTyr) residues, and two nanomaterial fluorophores, green-emissive CdS quantum dots (CdSQDs) and red-emissive gold nanoclusters (AuNCs), are cocaged in a bovine serum albumin (BSA) molecule. The large differences of Stokes shifts among diTyr residues, CdSQDs, and AuNCs ensure their emission at a single excitation wavelength. The nanoprobes can be facilely integrated using two-step synthetic reactions. DiTyr residues and AuNCs are formed and bound to the protein cage through the redox reaction between Au3+ and tyrosine residues of BSA, and the CdSQDs are followed to be conjugated to the modified BSA cage-templated CdS combination reaction. With established benign biocompatibility, the nanoprobes can ratiometrically detect intracellular glutathione by significantly enhancing the green emission of the conjugated CdSQDs. Likewise, the ratiometric sensing of solution alkalinity and tris(2-carboxyethyl)phosphine can be achieved using blue-emitted diTyr residues and red-emitted AuNCs as the responsive units, respectively, and the corresponding other two fluorophores as the reference signals. This study addresses a concept of trinity fluorescence ratiometric sensing system with multiple targets and optional references, which should be a promising pathway to meet the challenges from complexing biochemical environments and multivariate analysis.

Structural changes of serum albumin in response to oxidative stress caused byWalker-256 carcinosarcoma growth.

To assess oxidative stress and structural changes of the serum albumin in rats with transplanted Walker-256carcinosarcoma (W256) strains with varying sensitivity to doxorubicin (Dox). The study was performed on female Wistar rats with transplanted W256. On the 9th day after tumor cell transplantation an analysis of peripheral blood, oxidative stress parameters, and structural changes of serum albumin of experimental animals was performed. On the 9th day after W256transplantation a significant increase in the leukocyte counts was observed in the groups of animals with the Dox-resistant and parental (Dox-sensitive) W256tumors compared with the group of the intact animals: up to 14.24 ± 1.92•103/μl and 9.78 ± 1.03•103/μl, vs 8.92 ± 1.04•103/μl, respectively, due to the increase of granulocyte and monocyte counts. The number of lymphocytes was within the normal range. The level of hemoglobin and the erythrocyte counts were also within normal limits, but hematocrit in both groups of animals with tumors somewhat increased against the background of 1.2-fold elevation of the mean erythrocyte volume. In the group of rats with Dox-resistant W256, there was observed a decrease in the plateletcrit by almost 22% and thrombocyte counts- by 28%. Analysis of oxidative stress indices revealed a significant increase in the level of reactive oxygen species, 2-fold increase of malonic dialdehyde level and the degree of oxidative damage of blood plasma proteins, as well as a decrease in the activity of catalase in hemolysates (by 12-15%) in both groups of tumor-bearing rats. With the use of differential scanning calorimetry, UV and fluorescence spectroscopy we have revealed anomalous conformational changes of albumin caused by tumor development: structural rearrangements in the region of its first drug binding site located in the IIA domain, separation of globular parts of albumin molecule, and partial "opening" in a protein molecular three-domain structure resulting a loss of its thermal resistance. The development of transplanted Walker-256carcinosarcoma, especially its Dox-resistant variant, results in severe metabolic intoxication reflected in alteration of hematological parameters, and indices of oxidative stress, as well as architectonic changes of serum albumin.

Design of pH-Degradable Polymer-Lipid Amphiphiles Using a Ketal-Functionalized RAFT Chain Transfer Agent.

Conjugation of small molecule drug to lipid-polymer amphiphiles is a powerful strategy to alter the pharmacokinetic profile of these molecules by promoting binding to albumin or other serum molecules. Incorporation of a responsive linker between the lipid anchor and the polymer chain can be of interest to avoid indefinite binding of the conjugates to hydrophobic pockets of serum proteins or phospholipid membranes when reaching a target cell or tissue. Here, the synthesis of pH-sensitive lipid-polymer conjugates by reversible addition-fragmentation chain transfer (RAFT) polymerization using a RAFT chain transfer agent that is equipped with a pH-sensitive ketal bond between a cholesterol moiety and the trithiocarbonate RAFT chain transfer group is reported. It is demonstrated that in native form these conjugates exhibit a high affinity to albumin and cell membranes but loose this ability in response to a mild acidic trigger in aqueous medium.