Preparation and characterization of various PVPylated divalent metal-doped ferrite nanoparticles for magnetic hyperthermia.

There is an incessant demand to keep improving on the heating responses of polymeric magnetic nanoparticles (MNPs) under magnetic excitation, particularly in the pursuit for them to be utilized for clinical hyperthermia applications. Herein, we report the fabrication of a panel of PVP-capped divalent metal-doped MFe2O4 (M ≅ Co, Ni, Zn, Mg, and Sn) MNPs prepared via the Ko-precipitation Hydrolytic Basic (KHB) methodology and assess their magneto-thermal abilities. The physiochemical, structural, morphological, compositional, and magnetic properties of the doped ferrites were fully characterized using various techniques mainly TEM, XRD, EDX, FTIR, and VSM. The obtained doped MNPs exhibited stabilized quasi-spherical sized particles (10-17 nm), pure well-crystallized cubic spinel phases, and high saturation magnetizations (Ms = 26-81 emu g-1). In response to a clinically-safe alternating magnetic field (AMF) (f = 332.8 kHz and H = 170 Oe), distinctive heating responses of these doped ferrites were attained. Hyperthermia temperatures of 42 °C can be reached very fast in only ∼5 min, with heating temperatures slowly increasing to reach up to 55 °C. The highest heating performance was observed for PVP-NiFe2O4 and the lowest for PVP-Sn-doped NPs (SAR values: PVP-NiFe2O4 > PVP-CoFe2O4 > PVP-ZnFe2O4 > PVP-MgFe2O4 > PVP-SnFe2O4). This trend was found to be directly correlated to their observed magnetic saturation and anisotropy. Heating efficiencies and specific SAR values as functions of concentration, frequency, and amplitude were also systematically investigated. Finally, cytotoxicity assay was conducted on aqueous dispersions of the doped ferrite NPs, proving their biocompatibility and safety profiles. The PVPylated metal-doped ferrite NPs prepared here, particularly Ni- and Co-doped ferrites, are promising vehicles for potential combined magnetically-triggered biomedical hyperthermia applications.

MICaFVi: A Novel Magnetic Immuno-Capture Flow Virometry Nano-Based Diagnostic Tool for Detection of Coronaviruses.

COVID-19 has resulted in a pandemic that aggravated the world's healthcare systems, economies, and education, and caused millions of global deaths. Until now, there has been no specific, reliable, and effective treatment to combat the virus and its variants. The current standard tedious PCR-based tests have limitations in terms of sensitivity, specificity, turnaround time, and false negative results. Thus, an alternative, rapid, accurate, and sensitive diagnostic tool that can detect viral particles, without the need for amplification or viral replication, is central to infectious disease surveillance. Here, we report MICaFVi (Magnetic Immuno-Capture Flow Virometry), a novel precise nano-biosensor diagnostic assay for coronavirus detection which combines the MNP-based immuno-capture of viruses for enrichment followed by flow-virometry analysis, enabling the sensitive detection of viral particles and pseudoviruses. As proof of concept, virus-mimicking spike-protein-coated silica particles (VM-SPs) were captured using anti-spike-antibody-conjugated MNPs (AS-MNPs) followed by detection using flow cytometry. Our results showed that MICaFVi can successfully detect viral MERS-CoV/SARS-CoV-2-mimicking particles as well as MERS-CoV pseudoviral particles (MERSpp) with high specificity and sensitivity, where a limit of detection (LOD) of 3.9 µg/mL (20 pmol/mL) was achieved. The proposed method has great potential for designing practical, specific, and point-of-care testing for rapid and sensitive diagnoses of coronavirus and other infectious diseases.

Assessing the Heat Generation and Self-Heating Mechanism of Superparamagnetic Fe3O4 Nanoparticles for Magnetic Hyperthermia Application: The Effects of Concentration, Frequency, and Magnetic Field.

Magnetite nanoparticles (MNPs) exhibit favorable heating responses under magnetic excitation, which makes them particularly suited for various hyperthermia applications. Herein, we report the detailed self-heating mechanisms of MNPs prepared via the Ko-precipitation Hydrolytic Basic (KHB) methodology. The as-prepared MNPs were fully characterized using various spectroscopic techniques including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and vibrating sample magnetometry (VSM). MNPs exhibited stable 15 nm quasi-spherical small-sized particles, pure crystalline cubic Fe3O4 phases, high saturation magnetizations (Ms = ~40 emu·g-1), and superparamagnetic behavior. In response to alternating magnetic fields (AMFs), these MNPs displayed excellent self-heating efficiencies with distinctive heating responses, even when minimal doses of MNPs were used. Heating efficacies and specific absorption rate (SAR) values as functions of concentration, frequency, and amplitude were systematically investigated. Remarkably, within only a few minutes, MNPs (2.5 mg/mL) showed a rapid dissipation of heat energy, giving a maximum intrinsic loss power (ILP) of 4.29 nHm2/kg and a SAR of 261 W/g. Hyperthermia temperatures were rapidly reached in as early as 3 min and could rise up to 80 °C. In addition, Rietveld refinement, Langevin, and linear response theory (LRT) models were studied to further assess the magnetic and heating mechanisms. The LRT model was used to determine the Néel relaxation time (τR = 5.41 × 10-7 s), which was compared to the Brownian relation time value (τB = 11 × 10-7 s), showing that both mechanisms are responsible for heat dissipated by the MNPs. Finally, the cytotoxicity assay was conducted on aqueous dispersions of MNPs, indicating their biocompatibility and low toxicity. Our results strongly suggest that the as-prepared Fe3O4 MNPs are promising vehicles for potential magnetically triggered biomedical hyperthermia applications.

Synthesis of novel hybrid mesoporous gold iron oxide nanoconstructs for enhanced catalytic reduction and remediation of toxic organic pollutants.

The development of highly efficient, rapid, and recyclable nanocatalysts for effective elimination of toxic environmental contaminants remains a high priority in various industrial applications. Herein, we report the preparation of hybrid mesoporous gold-iron oxide nanoparticles (Au-IO NPs) via the nanocasting "inverse hard-templated replication" approach. Dispersed Au NPs were anchored on amine-functionalized iron oxide incorporated APMS (IO@APMS-amine), followed by etching of the silica template to afford hybrid mesoporous Au-IO NPs. The obtained nanoconstructs were fully characterized using electron microscopy, N2 physisorption, and various spectroscopic techniques. Owing to their magnetic properties, high surface areas, large pore volumes, and mesoporous nature (S BET = 124 m2 g-1, V pore = 0.33 cm3 g-1, and d pore = 4.5 nm), the resulting Au-IO mesostructures were employed for catalytic reduction of nitroarenes (i.e. nitrophenol and nitroaniline), two of the most common toxic organic pollutants. It was found that these Au-IO NPs act as highly efficient nanocatalysts showing exceptional stabilities (>3 months), enhanced catalytic efficiencies in very short times (∼100% conversions within only 25-60 s), and excellent recyclabilities (up to 8 cycles). The kinetic pseudo-first-order apparent reaction rate constants (k app) were calculated to be equal to 8.8 × 10-3 and 23.5 × 10-3 s-1 for 2-nitrophenol and 2-nitroaniline reduction, respectively. To our knowledge, this is considered one of the best and fastest Au-based nanocatalysts reported for the catalytic reduction of nitroarenes, promoted mainly by the synergistic cooperation of their high surface area, large pore volume, mesoporous nature, and enhanced Au-NP dispersions. The unique mesoporous hybrid Au-IO nanoconstructs synthesized here make them novel, stable, and approachable nanocatalyst platform for various catalytic industrial processes.

An easy, fast and inexpensive method of preparing a biological specimen for scanning electron microscopy (SEM).

Biological samples usually require cumbersome preparation steps before SEM imaging. Here we propose a simple, fast and inexpensive method to prepare and visualize biological cell culture samples in a few easy steps. We have tested this method with success on several adherent breast cancer and non-adherent leukemia cell lines. This method gives results comparable to other well-established techniques, and it can be convenient in day-to-day biological sample preparation for SEM imaging.•An easy and rapid method to visualize biological specimens under SEM.•Cells are grown on carbon tapes and gold coated.•Air drying without compromising the image quality.

Maghemite (γ-Fe2O3) and γ-Fe2O3-TiO2 Nanoparticles for Magnetic Hyperthermia Applications: Synthesis, Characterization and Heating Efficiency.

In this report, the heating efficiencies of γ-Fe2O3 and hybrid γ-Fe2O3-TiO2 nanoparticles NPs under an alternating magnetic field (AMF) have been investigated to evaluate their feasible use in magnetic hyperthermia. The NPs were synthesized by a modified sol-gel method and characterized by different techniques. X-ray diffraction (XRD), Mössbauer spectroscopy and electron microscopy analyses confirmed the maghemite (γ-Fe2O3) phase, crystallinity, good uniformity and 10 nm core sizes of the as-synthesized composites. SQUID hysteresis loops showed a non-negligible coercive field and remanence suggesting the ferromagnetic behavior of the particles. Heating efficiency measurements showed that both samples display high heating potentials and reached magnetic hyperthermia (42 °C) in relatively short times with shorter time (~3 min) observed for γ-Fe2O3 compared to γ-Fe2O3-TiO2. The specific absorption rate (SAR) values calculated for γ-Fe2O3 (up to 90 W/g) are higher than that for γ-Fe2O3-TiO2 (~40 W/g), confirming better heating efficiency for γ-Fe2O3 NPs. The intrinsic loss power (ILP) values of 1.57 nHm2/kg and 0.64 nHm2/kg obtained for both nanocomposites are in the range reported for commercial ferrofluids (0.2-3.1 nHm2/kg). Finally, the heating mechanism responsible for NP heat dissipation is explained concluding that both Neel and Brownian relaxations are contributing to heat production. Overall, the obtained high heating efficiencies suggest that the fabricated nanocomposites hold a great potential to be utilized in a wide spectrum of applications, particularly in magnetic photothermal hyperthermia treatments.

Iron Oxide Mesoporous Magnetic Nanostructures with High Surface Area for Enhanced and Selective Drug Delivery to Metastatic Cancer Cells.

This work reports the fabrication of iron oxide mesoporous magnetic nanostructures (IO-MMNs) via the nano-replication method using acid-prepared mesoporous spheres (APMS) as the rigid silica host and iron (III) nitrate as the iron precursor. The obtained nanosized mesostructures were fully characterized by SEM, TEM, DLS, FTIR, XRD, VSM, and nitrogen physisorption. IO-MMNs exhibited relatively high surface areas and large pore volumes (SBET = 70-120 m2/g and Vpore = 0.25-0.45 cm3/g), small sizes (~300 nm), good crystallinity and magnetization, and excellent biocompatibility. With their intrinsic porosities, high drug loading efficiencies (up to 70%) were achieved and the drug release rates were found to be pH-dependent. Cytotoxicity, confocal microscopy, and flow cytometry experiments against different types of cancerous cells indicated that Dox-loaded IO-MMNs reduced the viability of metastatic MCF-7 and KAIMRC-1 breast as well as HT-29 colon cancer cells, with the least uptake and toxicity towards normal primary cells (up to 4-fold enhancement). These results strongly suggest the potential use of IO-MMNs as promising agents for enhanced and effective drug delivery in cancer theranostics.

Preparation of iron oxide mesoporous magnetic microparticles as novel multidrug carriers for synergistic anticancer therapy and deep tumor penetration.

The preparation of mesoporous iron oxides with controllable physiochemical properties for effective therapeutic drug delivery remains a formidable challenge. Herein, iron oxide mesoporous magnetic microparticles (IO-MMMs) were prepared by a modified reverse hard-templating approach using, for the first time, acid-prepared mesoporous spheres (APMS) as the hard silica template. The obtained mesostructures exhibited remarkably high surface area and large pore volumes (SBET = 240 m2/g and Vpore = 0.55 cm3/g), controllable average sizes, generally uniform morphologies, and excellent biocompatibilities, allowing them to achieve optimal drug release in cancer cells and tumor tissues. IO-MMM carriers were able to co-load high amounts of hydrophilic chemotherapeutic drugs (Dox or Daun) and/or hydrophobic hormonal anticancer drugs (Tam), and release them sustainably in a pH-dependent manner, utilizing the fluorescence of Daun to real-time trace the intracellular drug distribution, and employing Daun/Tam to treat cancer by combined chemo/hormonal therapy. Cytotoxicity assays against different types of cancerous cells showed that the combinatory Daun/Tam@IO-MMM formulation significantly reduced the viability of metastatic MCF7 and KAIMRC1 breast as well as HCT8 colorectal cancer cells, with the least potency towards non-cancerous normal primary cells (up to 10-fold). Electron, flow, and live confocal microscopy imaging confirmed that the loaded vehicles were successfully and differentially uptaken by the different tested cells, gradually releasing their payloads, and causing apoptotic cell death. Importantly, compared to free drugs, Daun/Tam@IO-MMMs displayed enhanced drug accumulation in patient breast primary tumor tissues, deeply penetrating into the tumor region and killing the tumor cells inside. The designed carriers described here, thus, constitute a novel promising magnetic mesoporous smart system that entraps different kinds of drugs and release them in a controlled manner for combinatorial chemo/hormonal cancer theranostics. This multifactorial platform may open new avenues in cancer therapy as efficient synergistic antitumor system through overcoming limitations of conventional cancer therapy.

Magnetic iron oxide nanoparticles as drug carriers: preparation, conjugation and delivery.

Magnetic nanoparticles (MNPs), particularly made of iron oxides, have been extensively studied as diagnostic imaging agents and therapeutic delivery vehicles. In this review, special emphasis is set on the 'recent advancements of drug-conjugated MNPs used for therapeutic applications'. The most prevalent preparation methods and chemical functionalization strategies required for translational biomedical nanoformulations are outlined. Particular attention is, then, devoted to the tailored conjugation of drugs to the MNP carrier according to either noncovalent or covalent attachments, with advantages and drawbacks of both pathways conferred. Notable examples are presented to demonstrate the advantages of MNPs in respective drug-delivery applications. Understanding of the preparation, conjugation and delivery processes will definitely bring, in the next decades, a novel magneto-nanovehicle for effective theranostics.

Magnetic iron oxide nanoparticles as drug carriers: clinical relevance.

Significant preclinical and clinical research has explored the use of magnetic iron oxide nanoparticles (MNPs) for medical theranostics. Herein, we provide an overview of the optimal 'design-to-perform' MNPs used in cancer therapeutics, specifically focusing on magnetic hyperthermia, magnetic drug targeting, and targeting delivery. An account of the progress made in the clinic using MNPs is then analyzed. We place special emphasis on past and present magnetic nanoformulations used in clinical settings or yet to be clinically approved. Regrettably, as of now, no MNP drug delivery system is employed in the clinic. Thus, identifying current limitations, misconceptions and challenges will definitely impact the clinical success of MNP delivery theranostic systems and their promising future potential in medicine.

Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.

We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.

CD44 targeting magnetic glyconanoparticles for atherosclerotic plaque imaging.

PURPOSE: The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. METHODS: Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. RESULTS: The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. CONCLUSIONS: Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.

Enhanced enzymatic thermal stability and activity in functionalized mesoporous silica monitored by (31) p NMR.

Organophosphorus hydrolase (OPH) is immobilized on ammonium-modified mesoporous silica particles. Thermal stability and activity are measured with a (31) P NMR assay of the conversion of paraoxon (toxic) to its non-toxic hydrolysis product. After immobilization, OPH is significantly more active at room temperature and retained activity even after being heated to 45 °C for 1 month.

Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells.

Currently, there is high interest in developing multifunctional theranostic platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising system for targeted imaging and drug delivery. When incubated with cancer cells, HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer cells was much higher than the NPs without HA coating. The high magnetic relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the nanoparticles through an acid responsive linker. While HA-SPION was not toxic to cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug-sensitive but also multi-drug-resistant cancer cells. This was attributed to differential uptake mechanisms and cellular distributions of free DOX and DOX-HA-SPION in cancer cells.

Binding of HIV-1 gp120 glycoprotein to silica nanoparticles modified with CD4 glycoprotein and CD4 peptide fragments.

An important step in human immunodeficiency virus infection involves the interaction between the viral envelope glycoprotein gp120 and the human host cell surface receptor CD4. Herein, we describe a CD4-functionalized mesoporous silica-based system to selectively capture HIV-gp120 with high binding efficiency. Using a protection-deprotection strategy developed recently by our group, the external surface of the mesoporous particles was selectively functionalized with soluble CD4 ("sCD4") or an 18-peptide fragment mimicking the gp120 binding region. Confocal microscopy confirmed the CD4 locations and showed that the internal pores can be made accessible after external modification in a controlled manner. An evaluation of the ability of an 18-peptide CD4 fragment versus amide-immobilized sCD4 and sCD4 immobilized through its glycosidic group indicated that while all peptides were selective, the latter method was clearly best, with nearly complete removal of whole gp120 from solution. This study shows, for the first time, that sCD4 bound to mesoporous silica particles actively recognizes and retains high binding affinity for HIV-gp120. It is anticipated that, by proper modification of the accessible internal pores, our methodology can be adopted to develop porous platforms for HIV diagnosis, imaging, drug delivery, and vaccine development.

Glyco-nanomaterials: translating insights from the "sugar-code" to biomedical applications.

Over the past decade, diagnostics and therapeutics have changed gradually towards the use of more specific and targeted approaches. The most profound impact has been in the nanotechnology sectors, where an explosion in directing biomolecules to specific biomarkers has illustrated great potentials not only in detection but also in targeted therapy. Increased knowledge of the diseases at the molecular level catalyzed a shift towards identifying new biological indicators. In particular, carbohydrate-mediated molecular recognitions using nano-vehicles are likely to increasingly affect medicine opening a new area of biomedical applications. This article provides an overview of the recent progress made in recruiting the "sugar code" functionalized on various nano-platforms to decipher cellular information for both in vitro and in vivo applications. Today's glyco-technologies are enabling better detection with great therapeutic potentials. Tomorrow they are likely to bring a full understanding of the "cell-glyconanomaterial bio-conversation" where major biomedical problems will be overcome translating insights from the "glyco-nanoworld" into clinical practice.

A simple method for the synthesis of hyaluronic acid coated magnetic nanoparticles for highly efficient cell labelling and in vivo imaging.

Highly stable colloidal hyaluronic acid coated magnetic nano-particles were prepared via a ligand exchange method. These particles exhibited excellent cell labeling efficiencies and superior potential as MRI contrast agents, which are useful to target tumor cells expressing hyaluronic acid receptors such as CD44.

Hyaluronic acid immobilized magnetic nanoparticles for active targeting and imaging of macrophages.

Imaging and targeted delivery to macrophages are promising new approaches to study and treat a variety of inflammatory diseases such as atherosclerosis. In this manuscript, we have designed and synthesized iron oxide based magnetic nanoparticles bearing hyaluronic acid (HA) on the surface to target activated macrophages. The HA-coated nanoparticles were prepared through a co-precipitation procedure followed by postsynthetic functionalization with HA and fluorescein. The nanoparticles were characterized by transmission electron microscopy, thermogravimetric analysis, elemental analysis, dynamic light scattering, and high-resolution magic angle spinning NMR and were biocompatible with cells and colloidally stable in the presence of serum. The HA immobilized on the nanoparticles retained their specific biological recognition with the HA receptor CD44, which is present on activated macrophages in high-affinity forms. Cell uptake studies demonstrated significant uptake of HA nanoparticles by activated macrophage cell line THP-1, which enabled magnetic resonance imaging of THP-1 cells. The uptake of nanoparticles was found to be both HA and CD44 dependent. Interestingly, Prussian blue staining showed that the magnetite cores of the HA-coated nanoparticles were only transiently present inside the cells, thus reducing the potential concerns of nanotoxicity. Furthermore, fluorescein on the nanoparticle was found to be delivered to the cell nucleus. Therefore, with further development, these HA functionalized magnetic nanoparticles can potentially become a useful carrier system for molecular imaging and targeted drug delivery to activated macrophages.

Magnetic glyco-nanoparticles: a tool to detect, differentiate, and unlock the glyco-codes of cancer via magnetic resonance imaging.

Within cancer, there is a large wealth of diversity, complexity, and information that nature has engineered rendering it challenging to identify reliable detection methods. Therefore, the development of simple and effective techniques to delineate the fine characteristics of cancer cells can have great potential impacts on cancer diagnosis and treatment. Herein, we report a magnetic glyco-nanoparticle (MGNP) based nanosensor system bearing carbohydrates as the ligands, not only to detect and differentiate cancer cells but also to quantitatively profile their carbohydrate binding abilities by magnetic resonance imaging (MRI). Using an array of MGNPs, a range of cells including closely related isogenic tumor cells, cells with different metastatic potential and malignant vs normal cells can be readily distinguished based on their respective "MRI signatures". Furthermore, the information obtained from such studies helped guide the establishment of strongly binding MGNPs as antiadhesive agents against tumors. As the interactions between glyco-conjugates and endogenous lectins present on cancer cell surface are crucial for cancer development and metastasis, the ability to characterize and unlock the glyco-code of individual cell lines can facilitate both the understanding of the roles of carbohydrates as well as the expansion of diagnostic and therapeutic tools for cancer.

Lipoic acid glyco-conjugates, a new class of agents for controlling nonspecific adsorption of blood serum at biointerfaces for biosensor and biomedical applications.

The carbohydrate-derived lipoic acid derivatives were studied as protein and cell resistant biomaterials. Six types of carbohydrates were examined for their abilities to reduce nonspecific adsorption of human serum and Hela cell using quartz crystal microbalance. Our data suggested that the structures of carbohydrates play an important role in resisting nonspecific binding. Specifically, the resistance was found to increase in the order lipoic fucose < lipoic mannose < lipoic N-acetyl glucosamine < lipoic glucose < lipoic sialic acid < lipoic galactose, where lipoic galactose derivative resisted most nonspecific adsorption. Furthermore, the combination of lipoic galactose and BSA was the most effective in reducing the adsorption of even undiluted human serum and the attachment of Hela cells while allowing specific binding. Several control experiments have demonstrated that the resistant-ability of mixed lipoic galactose and BSA was comparable to the best known system for decreasing nonspecific adsorption.