A one-step highly sensitive method for DNA detection using dynamic light scattering

A one-step homogeneous DNA detection method with high sensitivity was developed using gold nanoparticles (AuNPs) coupled with dynamic light scattering (DLS) measurement. Citrate-protected AuNPs with a diameter of 30 nm were first functionalized with two sets of single-stranded DNA probes and then used as optical probes for DNA detection. In the presence of target DNA, the hybridization between target DNA and the two nanoparticle probes caused the formation of nanoparticle dimers, trimers, and oligomers. As a result, the nanoparticle aggregation increased the average diameter of the whole nanoparticle population, which can be monitored simply by DLS measurement. A quantitative correlation can be established between the average diameter of the nanoparticles and the target DNA concentration. This DLS-based assay is extremely easy to conduct and requires no additional separation and amplification steps. The detection limit is around 1 pM, which is 4 orders of magnitude better than that of light-absorption-based methods. Single base pair mismatched DNAs can be readily discriminated from perfectly matched target DNAs using this assay.     

Homogeneous immunoassay based on aggregation of antibody-functionalized gold nanoparticles coupled with light scattering detection

A universal platform of homogeneous noncompetitive immunoassay, using human immunoglobulin (IgG) as a model analyte, has been developed. The assay is based on aggregation of antibody-functionalized gold nanoparticles directed by the immunoreaction coupled with light scattering detection with a common spectrofluorimeter. In phosphate buffer (pH 7.0) solution, the light scattering intensity of the gold nanoparticles functionalized with goat-anti-human IgG can be greatly enhanced by addition of the human IgG. Based on this phenomenon, a wide dynamic range of 0.05-10 microg ml(-1) for determination of human IgG can be obtained, and the detection limit can reach 10 ng ml(-1). The proposed immunoassay can be accomplished in a homogeneous solution with one-step operation within 10 min and has been successfully applied to the determination of human IgG in serum samples, in which the results are well consistent with those of the enzyme-linked immunosorbent assay (ELISA), indicating its high selectivity and practicality. Therefore, the gold nanoparticle-based light scattering method can be used as a model to establish the general methods for protein assay in the fields of molecular biology and clinical diagnostics.     

Characterization of nanoparticles in diluted clear solutions for Silicalite-1 zeolite synthesis using liquid 29Si NMR, SAXS and DLS

Clear solutions for colloidal Silicalite-1 synthesis were prepared by reacting tetraethylorthosilicate in aqueous tetrapropylammonium hydroxide solution. A dilution series with water resulting in clear solutions with a TEOS ratio TPAOH ratio H2O molar ratio of 25 : 9 : 152 up to 25 : 9 : 15,000 was analysed using liquid 29Si nuclear magnetic resonance (NMR), synchrotron small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Particle sizes were derived independently from DLS and from the combination of SAXS and NMR. NMR allowed quantitative characterization of silicon distributed over nanoparticles and dissolved oligomeric silicate polyanions. In all samples studied, the majority of silicon (78-90%) was incorporated in the nanoparticle fraction. In concentrated suspensions, silicate oligomers were mostly double-ring species (D3R, D4R, D5R, D6R). Dilution with water caused their depolymerisation. Contrarily, the internal condensation and size of nanoparticles increased with increasing dilution. SAXS revealed a decrease of effective nanoparticle surface charge upon dilution, reducing the effective particle interactions. With DLS, the reduction of nanoparticle interactions could be confirmed monitoring the collective diffusion mode. The observed evolution of nanoparticle characteristics provides insight in the acceleration of the Silicalite-1 crystallization upon dilution, in view of different crystallization models proposed in the literature.     

A facile one-pot method to fabricate gold nanoparticle chains with dextran

A biocompatible water-soluble dextran has been used for controllable one-dimensional assembly of gold nanoparticles via a one-pot method.Long gold nanoparticle chains with good dispersion in water could be easily obtained after adding dextran into the mixture of HAuCl 4 and sodium citrate.The measurements of scanning electron microscopy(SEM) and dynamic light scattering(DLS) confirmed the formation of gold nanoparticle chains.The morphology and dispersion properties of gold nanoparticle chains could be tuned by adjustment of the reagent ratio,stirring speed,and reaction time.     

Fast protein detection using absorption properties of gold nanoparticles

In this study we describe the use of gold nanoparticles as a fast detection system for the sensitive analysis of proteins. The immunological method allows for protein analysis at the nanogram level, as required for clinical diagnosis. Initially a test protein is used for the development of the assay. The system is subsequently adopted for alpha-fetoprotein, which is a relevant tumor marker. This work demonstrates that antibody functionalized gold nanoparticles can be used for the detection of proteins by forming gold nanoparticle aggregates. The influence of the size of the gold nanoparticles on the sensitivity of the assay is investigated in the range from 20-60 nm particles; the larger particles show here the highest relative changes. The formation of antigen-gold nanoparticle aggregates is detected by an increase in hydrodynamic diameter by dynamic light scattering (DLS). UV/Vis spectroscopy also allows assay monitoring by quantifying the red shift of the plasmon resonance wavelength. Alpha-fetoprotein can be analysed in the concentration range of 0.1-0.4 μg ml(-1). The influence of pH, ionic strength and ratio of sample to Au-NP solution is studied. With this method, the protein AFP can be rapidly detected as demanded for clinical diagnosis.     

Single particle technique for one-step homogeneous detection of cancer marker using gold nanoparticle probes

In this paper, we reported a single particle technique for the one-step homogeneous immunoassay of a cancer marker by resonance light scattering correlation spectroscopy (RLSCS). The setup of RLSCS was similar to fluorescence correlation spectroscopy (FCS), and its principle was based on measuring the resonance light scattering fluctuations in a small volumes (less than 1 fL) due to Brownian motion of single particles. In homogeneous immunoassay, we used a sandwich strategy and conjugated two different antibodies (Ab) with gold nanoparticles (GNPs) respectively. When two different GNPs labeled with antibodies are mixed in a sample containing antigen (Ag) targets, the binding of targets will cause GNPs to form dimers (or oligomers), which leads to the significant increase in the characteristic diffusion time of GNPs in the detection volume. The RLSCS method can sensitively detect the change in the characteristic diffusion time of GNPs before and after immune reactions. We used this technology in homogeneous immunoassays for the liver cancer biomarker alpha-fetoprotein (AFP). The conditions of the immune reaction were investigated systematically. In the optimal conditions, the linear range of this assay is from 1 pM to 1 nM and the detection limit is 1 pM for AFP. This new method was successfully applied for the direct determination of AFP levels in sera from healthy subjects and cancer patients. Our results were in good agreement with ELISA assays.     

Dense aqueous colloidal gold nanoparticles prepared from highly concentrated precursor solution

Gold nanoparticles were fabricated by reduction of highly concentrated Au(III) ions (200 mM) with casein proteins from milk. The gold nanoparticles were converted to nanoparticle-powders after washing and subsequent vacuum drying without aggregation. The nanoparticle-powders completely re-dispersed in aqueous solution, and stable colloidal gold nanoparticles were obtained. UV-vis extinction spectra and dynamic light scattering (DLS) measurements revealed that large assemblies (size, ca. 3 μm) and subaggregates (size, <0.5 μm) composed of gold nanoparticle-casein protein chain-Au(III) ion were dynamically formed and disintegrated over the course of the growth of the gold nanoparticles. Fourier transform infrared (FT-IR) spectra indicated conformational changes of casein proteins induced by the interaction of casein protein-Au(III) ion and -gold nanoparticle. Finally, rapid, one-pot, and highly concentrated synthetic procedures of gold and silver nanoparticle powders protected by casein (mean diameters below 10 nm) were successfully developed using 3-amino-1-propanol aqueous solutions as reaction media. Dense colloidal gold (40 g L(-1)) and silver (22 g L(-1)) nanoparticle aqueous solutions were obtained by re-dispersing the metal nanoparticle powders.     

Thermal-induced growth of gold nanoparticles conjugated with thermoresponsive polymer without chemical reduction

The growth of gold nanoparticles without chemical reduction of gold (III) ions was achieved by the disruption of thermoresponsive polymers conjugated with the gold nanoparticles through the phase transition of the polymers. When a solution of gold nanoparticles coated with thermoresponsive polymers was heated, chains of the thermoresponsive polymers were disrupted because of dehydration, resulting in the fusion of gold nanoparticles to form larger nanoparticles. The evolution of the extinction band around 550 nm evidenced the formation of these large (post-fusion) gold nanoparticles, which were characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). TEM images verified the formation of the large gold nanoparticles having particle sizes of 80-100 nm, whereas DLS indicated the existence of large nanoparticles with hydrodynamic diameters exceeding 200 nm. The deposition did not require the addition of reductants or trivalent gold ions for the formation of the large gold nanoparticles. Both the heating and the solution conditions were studied to elucidate the mechanism of the formation of large gold nanoparticles.     

Investigation of the Mechanism of Colloidal Silicalite‐1 Crystallization by Using DLS,SAXS, and 29Si NMR Spectroscopy

Colloidal silicalite‐1 zeolite was crystallized from a concentrated clear sol prepared from tetraethylorthosilicate (TEOS) and aqueous tetrapropylammonium hydroxide (TPAOH) solution at 95 °C. The silicate speciation was monitored by using dynamic light scattering (DLS), synchrotron small‐angle X‐ray scattering (SAXS), and quantitative liquid‐state ²⁹Si NMR spectroscopy. The silicon atoms were present in dissolved oligomers, two discrete nanoparticle populations approximately 2 and 6 nm in size, and crystals. On the basis of new insight into the evolution of the different nanoparticle populations and of the silicate connectivity in the nanoparticles, a refined crystallization mechanism was derived. Upon combining the reagents, different types of nanoparticles (ca. 2 nm) are formed. A fraction of these nanoparticles with the least condensed silicate structure does not participate in the crystallization process. After completion of the crystallization, they represent the residual silicon atoms. Nanoparticles with a more condensed silicate network grow until approximately 6 nm and evolve into building blocks for nucleation and growth of the silicalite‐1 crystals. The silicate network connectivity of nanoparticles suitable for nucleation and growth increasingly resembles that of the final zeolite. This new insight into the two classes of nanoparticles will be useful to tune the syntheses of silicalite‐1 for maximum yield.     

On the measurement of gold nanoparticle sizes by the dynamic light scattering method

The application of the dynamic light scattering (DLS) method for determining the size distribution of colloidal gold nanoparticles in a range of 1–100 nm is discussed. It is shown that rotational diffusion of nonspherical strongly scattering particles with sizes of larger than 30–40 nm results in the appearance of a false peak in a size range of about 5–10 nm. In this case, the uncritical application of the DLS method may yield particle volume or number size distributions different from those obtained by transmission electron microscopy. For weakly scattering particles with diameters of smaller that 20 nm, the DLS method demonstrates an additional peak of intensity distribution in the region of large sizes that is related to particle aggregates or byproduct particles rather than individual nanoparticles. Practical methods for solving the problem of false peaks are discussed. It is established that the width of the DLS distribution does not correspond to transmission electron microscopy data and is overestimated. The advantages and drawbacks of the methods are compared and it is noted that, at present, the DLS method is the only instrument suitable for nonperturbative and sensitive diagnostics of relatively slow aggregation processes with characteristic times on the order of 1 min. In particular, this method can be used to diagnose gold nanoparticle conjugate aggregation initiated by biospecific interactions on their surface.     

Preparation of crystalline gold nanoparticles at the surface of mixed phosphatidylcholine-ionic surfactant vesicles

The formation of gold nanoparticles and the crystal growth at the surface of mixed phosphatidylcholine (PC)-ionic surfactant vesicles was investigated. The PC-bilayer surface was negatively charged by incorporating sodium dodecyl sulfate (SDS) and positively charged by adding hexadecyltrimethylammonium chloride (CTAB). The mass ratio phosphatidylcholine:surfactant was fixed in both cases at 1:1. The gold nanoparticle formation was studied by using transmission electron microscopy (TEM) combined with dynamic light scattering (DLS) and UV-vis absorption spectroscopy. TEM micrographs confirm that the particle formation occurs on the vesicle surface. However, the reduction process depends on the ionic surfactant incorporated into the vesicles, the vesicle size distribution, as well as the temperature used for the reduction process. Thereby, it becomes possible to control the crystal growth of the individual spherical gold nanoparticles in a characteristic way. Red colored colloidal dispersions consisting of monodisperse spherical nanoparticles with an average particle size between 2 and 8 nm (determined by dynamic light scattering) can be obtained by using a monodisperse SDS-modified vesicle phase. When the temperature is increased to 45 degrees C, a crystallization in rod-like or triangular structures is observed. In the CTAB-based template phase in general larger gold particles of about 35 nm are formed. In similarity to the anionic vesicles a temperature increase leads to the crystallization in triangular structures.     

Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine

The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.     

Preparation of sterically stabilized gold nanoparticles for plasmonic applications

Plasmonic nanoparticles such as those of gold or silver have been recently investigated as a possible way to improve light absorption in thin film solar cells. Here, a simple method for the preparation of spherical plasmonic gold nanoparticles in the form of a colloidal solution is presented. The nanoparticle diameter is controlled in the range from several nm to tens of nm depending on the synthesis parameters with the size dispersion down to 14 %. The synthesis is based on thermal decomposition and reduction of the chloroauric acid in the presence of a stabilizing capping agent (surfactant) that is very slowly injected into the hot solvent. The surfactant prevents uncontrolled nanoparticle aggregation during the growth process. The nanoparticle size and shape depend on the type of the stabilizing agent. Surfactants with different lengths of the hydrocarbon chains such as Z-octa-9-decenylamine (oleylamine) with AgNO₃ and polyvinylpyrrolidone with AgNO₃ were used for the steric stabilization. Hydrodynamic diameter of the gold nanoparticles in the colloidal solution was determined by dynamic light scattering while the size of the nanoparticle metallic core was found by small-angle X-ray scattering. The UV-VIS-NIR spectrophotometer measurements revealed a plasmon resonance absorption in the 500–600 nm range. Self-assembled nanoparticle arrays on a silicon substrate were prepared by drop casting followed by spontaneous evaporation of the solvent and by a modified Langmuir-Blodgett deposition. The degree of perfection of the self-assembled arrays was analyzed by scanning electron microscopy and grazing-incidence small-angle X-ray scattering. Homogeneous close-packed hexagonal ordering of the nanoparticles stretching over large areas was evidenced. These results document the viability of the proposed nanoparticle synthesis for the preparation of high-quality plasmonic templates for thin film solar cells with enhanced power conversion efficiency, surface enhanced Raman scattering, and other applications.     

Electrochemical nucleation of gold nanoparticles in a polymer film at a liquid-liquid interface

Simultaneous nucleation of gold nanoparticles and polymerization of tyramine has been carried out at an immiscible electrolyte interface. By transferring the gold ion of tetraoctylammoniumtetracloroaurate (TOAAuCl(4)) from the organic to the aqueous phase, a fast homogeneous electron transfer from the tyramine monomer reduces the gold ion. Electropolymerization then proceeds, and gold nanoparticles form. The newly formed nanoparticles act as nucleation sites for the deposition of the oligomers/polymer (and possibly vice versa). This results in gold nanoparticles stabilized in a polytyramine matrix. The size of the nanoparticles is controlled by the concentration of oligomers/polymer in solution. The polymer nanoparticle composite film was analyzed with TEM, XPS, and AFM.     

Change Color Effect and Spectral Properties of Gold Nanoparticle-cationic Surfactants System

The change color effect of gold nanoparticle solutions was studied by means of resonance scattering and absorption spectrometry and scan electron microscopy. The red Au nanoparticles with a size of 10 nm exhibit a resonance absorption peak and a resonance scattering peak all at 525 nm. After some inorganic electrolyte was added to a red Au nanoparticles solution, the color of the solution became blue and the absorbance at 600-700 nm was significantly increased. The ratio of the concentration of rnonovalent cations, at which the resonance scattering of the system at 525 nm is maximal to that of divalent cations, is in the range of 100 : 1--100 ; 1. 8. It is in good agreement with the Schulze-Hardy rule of the coagulation value of electrolyte. After adding some cationic surfactants to the above solution, the color of the solution is in deep blue, with two resonance absorption peaks at 550 and 680 nm, and a greatly enhanced resonance scattering peak at 525 nm. The experiments demonstrate that the stronger the hydrophobicity of the cationic surfactant is, the stronger the change color effect of the Au nanoparticle solution promoted by cationic surfactant is. The change color effect of Au nanoparticle solution is resulted from the increased diameter of Au nanoparticles, and the changes of resonance absorotion DeaR and resonance scattering.     

Architecture of linear arrays of fluorinated co-oligomeric nanocomposite-encapsulated gold nanoparticles: a new approach to the development of gold nanoparticles possessing an extremely red-shifted absorption characteristic

Fluoroalkyl end-capped co-oligomeric nanoparticles, which were prepared by the reaction of fluoroalkanoyl peroxide with 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and 1-hydroxy-5-adamantylacrylate (Ad-HAc), were applied to the preparation of novel fluorinated co-oligomeric nanocomposite-encapsulated gold nanoparticles. These fluorinated gold nanocomposites were easily prepared by the reductions of gold ions with poly(methylhydrosiloxane) (PMHS) in the presence of the corresponding fluorinated nanoparticles and tri -n-octylamine (TOA) in 1,2-dichloroethane (DE) at room temperature. These fluorinated gold nanoparticles were isolated as wine-red powders and were found to exhibit good dispersibility in a variety of traditional organic solvents such as DE, methanol, and t-butyl alcohol to afford transparent wine-red solutions. The morphology and stability of these fluorinated co-oligomeic nanocomposite-encapsulated gold nanoparticles were characterized using transmission electron microscopy (TEM), dynamic light scattering measurements (DLS), and UV-vis spectroscopy. DLS measurements and UV-vis spectroscopy showed that these particles are nanometer-size-controlled very fine nanoparticles (185-218 nm) that exhibit a plasmon absorption band at around 530 nm. TEM images also showed that gold nanoparticles are tightly encapsulated into fluorinated co-oligomeric nanoparticle cores. Interestingly, these fluorinated co-oligomeric nanocomposites-encapsulated gold nanoparticles were found to afford linear arrays of these fluorinated nanoparticles with increases in the feed amounts of TOA. More interestingly, these fluorinated gold nanoparticles were able to afford the extremely red-shifted plasmon absorption band at around 960 nm.     

A biologically friendly single step method for gold nanoparticle formation

There has been a keen interest for developing a biologically friendly approach for the preparation of gold nanoparticles for their application reasons. A biocompatible, quick and single step method is established for the preparation of gold nanoparticles in lecithin (Egg phosphatidylcholine)/water systems where lecithin itself acts as a reductant for hydrogen tetrachloro aurate (HAuCl(4)) to form the gold nanoparticles. Small gold nanoparticles (5-7 nm in diameter) were prepared in lamellar phases formed by lecithin within 6-7h of HAuCl(4) addition. Sonication of aqueous mixture of lecithin/HAuCl(4) reduces the time of reduction process to seconds when a sonicator with probe (100 W) is used. Most of the particles are found attached to lecithin structures and are comparatively large in size. Some 10nm particles are found attached to small lecithin vesicles (～100 nm) formed during sonication. The nanoparticles formed were stabilized by an anionic surfactant sodium dodecylsulfate (SDS) which proved to be a good stabilizer, the nanoparticles being stable up to six months. To the best of our knowledge, this is the first report where a biological surfactant lecithin itself has acted as a reductant and no other chemical reductants were required for the gold nanoparticle formation. Particles were characterized by Uv-vis spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Lamellar phases were characterized by a polarizing microscope.     

金纳米粒子表面自组装巯基十一烷醇单分子层体系的制备及其光散射特性研究

采用柠檬酸钠还原法制备了水相金纳米粒子, 通过巯基的自组装, 成功获得了巯基十一烷醇(MUN)单分子层保护的金纳米粒子. 用紫外可见光谱、透射电子显微镜、激光散射粒度分析、同步散射光谱和发射光谱等手段对组装前后的金纳米粒子的性质进行了研究. 结果表明: 制备的金纳米粒子最大吸收波长518 nm, 形状规则, 粒度均匀, 平均粒径为14.6 nm, 每个粒子含有约9.64×10⁴原子; 组装之后的金纳米粒子表面等离子体共振吸收峰红移17.0 nm, 平均粒径增大为20.2 nm, 组装层的平均厚度2.8 nm, 与MUN分子长度相当, 结合量实验证明每一个金纳米粒子可以结合约7.52×10³个MUN, 表面覆盖率为83.6%, 粒子分散均匀, 稳定性增强可长期保存; 同步散射光谱变化和发射光谱中分频、差频和倍频峰的存在证明, 金纳米粒子组装前后均具有非线性光学特性.     

Direct visual detection of DNA based on the light scattering of silica nanoparticles on a human papillomavirus DNA chip

A detection system for a human papillomavirus (HPV) DNA chip based on the light scattering of aggregated silica nanoparticle probes is presented. In the assay, a target HPV DNA is sandwiched between the capture DNA immobilized on the chip and the probe DNA immobilized on the plain silica nanoparticle. The spot where the sandwich reaction occurs appears bright white and is readily distinguishable to the naked eye. Scanning electron microscopy images clearly show the aggregation of the silica nanoparticle probes. When three different sized (55 nm, 137 nm, 286 nm) plain silica nanoparticles were compared, probes of the larger silica nanoparticles showed a higher scattering intensity. Using 286-nm silica nanoparticles, the spots obtained with 200 pM of target DNA were visually detectable. The demonstrated capability to detect a disease related target DNA with direct visualization without using a complex detection instrument provides the prerequisite for the development of portable testing kits for genotyping.     

NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl'om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Tr...