Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free amine groups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH(2), -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929 fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T(2)-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929 fibroblast cells.     

纳米水基磁性液体在肿瘤治疗领域的研究进展

结合作者在纳米磁性液体方面的研究经历,介绍了生物医学应用领域纳米磁性粒子的组成结构及特点,指出高分子改性纳米磁性粒子具有生物相容性好、稳定性强、载药量高的优点,并对目前高分子改性纳米四氧化三铁颗粒的制备方法及特点进行了对比分析。指出进一步研制磁响应性强、载药量高、粒度分布均匀的纳米磁性粒子,使之对癌细胞具有亲和作用,尽量避免对毛细血管网状内皮系统的清除,是未来肿瘤治疗领域纳米磁性粒子的研发目标,并对目前制备方法中存在的不足提出了改进的建议。     

Selective internalization of ZnAl-HTlc nanoparticles in normal and tumor cells. A study of their potential use in cellular delivery

A colloidal dispersion of zinc aluminum hydrotalcite nanoparticles (ZnAl-HTlc) has been used for in vitro experimental procedures in order to provide reliable data on their potential application in cellular delivery. Two different cell lines (HeLa tumor cells and MDCK normal cells) with a similar epithelial derivation have been used. Sedimentation studies performed in the presence of different constituents of the cell culture medium revealed the importance of serum components to stabilize the colloidal dispersions of nanosized ZnAl-HTlc. Cell viability assay showed for nanosized ZnAl-HTlc a higher cell growth inhibition on tumor cells compared to normal cells whereas LDH test showed the absence of toxicity for both cell lines. Cellular uptake experiments indicated a preferential internalization of ZnAl-HTlc nanoparticles in HeLa tumor cells. Adsorption study and steady state fluorescence measurements on the phenol red/HTlc hybrid were carried out in order to verify the possibility of using phenol red as fluorescent dye for ZnAl-HTlc nanoparticles. The observed spectral behavior indicated a strong interaction between the dye and the inorganic matrix and the preferential adsorption of the dye on the nanoparticle surface has been confirmed by the XRPD data. Fluorescence confocal imaging showed a different localization pattern of nanosized HTlc in the two cell lines and a higher fluorescence signals in tumor cells supporting the occurrence of more efficient internalization processes in the pathogen cell line as observed in the cellular uptake experiments.     

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

A synthetic method to prepare a core-shell-structured Fe₃O₄@SiO₂ as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe₃O₄@SiO₂-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy.     

Folic acid-modified iridium(III) coordination polymeric nanoparticles facilitating intracellular release of a phosphorescent residue capable of nuclear entry

Functional polymeric nanoparticles with folic acid end-capped poly(ethylene glycol) (PEG) as the shell and an iridium(III) complex coupled with poly(4-vinylpyridine) (P4VP)/[Ir(pq)₂] (pq = 2-phenylquinoline) as the core have been prepared through complexation of the pyridine moiety with [Ir(pq)₂]₂⁺ followed by dialysis against water. The nanoparticles with folic acid on the surface are capable of entering HeLa cells. It is significant that, after cellular internalization, the intracellular compound histidine can trigger release of the [Ir(pq)₂]⁺ residue into the nucleus from the nanoparticles. This provides a new pathway for triggering the release of drugs from their carriers.     

A Novel Yolk–Shell Fe3O4@ Mesoporous Carbon Nanoparticle as an Effective Tumor-Targeting Nanocarrier for Improvement of Chemotherapy and Photothermal Therapy

Owing to their good stability and high photothermal conversion efficiency, the development of carbon-based nanoparticles has been intensively investigated, while the limitation of unsatisfactory cellular internalization impedes their further clinical application. Herein, we report a novel strategy for fabrication of Fe₃O₄ yolk–shell mesoporous carbon nanocarriers (Fe₃O₄@hmC) with monodispersity and uniform size, which presented significantly higher cell membrane adsorption and cellular uptake properties in comparison with common solid silica-supported mesoporous carbon nanoparticles with core–shell structure. Moreover, the MRI performance of this novel Fe-based nanoparticle could facilitate precise tumor diagnosis. More importantly, after DOX loading (Fe₃O₄@hmC-DOX), owing to synergistic effect of chemo–phototherapy, this therapeutic agent exhibited predominant tumor cell ablation capability under 808 nm NIR laser irradiation, both in vitro and in vivo. Our work has laid a solid foundation for therapeutics with hollowed carbon shell for solid tumor diagnosis and therapy in clinical trials.     

Versatile hybrid polyethyleneimine–mesoporous carbon nanoparticles for targeted delivery

To meet the needs of targeted drug delivery and medical imaging, uniform mesoporous carbon spheres (UMCS) were functionalized using hyperbranched polyethyleneimine (PEI) covalently linked with fluorescein isothiocyanate (FITC) and folic acid (FA). Folate-receptor-positive KB cancer cells internalized five times more nanoparticles than A549 cells deficient in folate receptors in vitro using flow cytometry and confocal microscopy. The in vivo distribution results also confirmed that the FA–PEI–FITC–UMCS nanoparticles could target the FA-positive tumors. In addition, the specifically targeted hybrid carbon nanoparticles exhibited non-cytotoxic and controlled intracellular release (pH dependent) of the loaded agents. The in vivo antitumor effect of the paclitaxel (PTX)-loaded nanoparticles was investigated in Kunming mice harboring a hepatic H22 tumor. PTX-loaded FA–PEI–UMCS nanoparticles displayed superior antitumor effects compared to other PTX formulations, and the tumor growth inhibition rate was 86.53% compared with the control group (saline) for the enhanced targeted accumulation of NPs in tumor cells.     

Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles

Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized via reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 μg ml(-1) for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.     

PEG-templated mesoporous silica nanoparticles exclusively target cancer cells

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.     

Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe₃O₄-NH₂, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.     

一种制备唾液酸磁性表面分子印迹聚合物的新方法

一锅法合成氨基化磁性纳米颗粒Fe₃O₄@NH₂,与对甲酰基苯硼酸(FPBA)反应嫁接硼酸官能团,通过硼酸基与模板唾液酸Neu5Ac分子上的顺式二醇共价反应,将Neu5Ac定向固定于磁性纳米颗粒。以多巴胺(DA)及3-氨基苯硼酸(3-APBA)为功能单体,自聚合反应形成共聚壳层包覆在磁性纳米颗粒的表面,制备得Neu5Ac磁性分子印迹聚合物(Neu5Ac-MMIPs)。通过透射电镜、红外光谱对其形态及结构进行表征,并评价其吸附性能。结果表明,Neu5Ac磁性分子印迹聚合物对Neu5Ac具有较好的吸附量、印迹效率、特异性等优点。通过对Neu5Ac至少5次吸附-洗脱的循环实验表明,MMIPs具有较好的重复再利用能力。     

Carrier-free, water dispersible and highly luminescent dye nanoparticles for targeted cell imaging

We develop a new strategy of using surface functionalized small molecule organic dye nanoparticles (NPs) for targeted cell imaging. Organic dye (2-tert-butyl-9,10-di(naphthalen-2-yl)anthracene, TBADN) was fabricated into NPs and this was followed by surface modification with an amphipathic surfactant poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG) through hydrophobic interactions to achieve good water dispersibility and bio-environmental stability. It should be noted that no additional inert materials were added as carriers, thus the dye-loading capacity of the resulting TBADN NPs is obviously higher than those of previously reported carrier-based structures. This would lead to much larger absorption and then much higher brightness. The resulting TBADN NPs possess comparable, if not higher, brightness than CdSe/ZnS quantum dots under the same conditions, with favorable biocompatibility. Significantly, TBADN NPs are readily conjugated with folic acid, and successfully applied in targeted cell imaging. These results show that water dispersible and highly stable organic NPs would be a promising new class of fluorescent probe for bioapplications in cellular imaging and labeling. This strategy may be straightforwardly extended to other organic dyes to achieve water dispersible NPs for cell imaging and drug delivery.     

Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol) ethyl ether methacrylate-co-poly(ethylene glycol) methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly-N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth) even at high iron concentrations (6 mM), indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA) approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury.     

Curcumin Loaded Nanocarriers with Varying Charges Augmented with Electroporation Designed for Colon Cancer Therapy

(1) Background: The size and surface charge are the most significant parameters of nanocarriers that determine their efficiency and potential application. The poor cell uptake of encapsulated drugs is the main limitation in anticancer treatment. The well-defined properties of nanocarriers will enable to target specific tissue and deliver an active cargo. (2) Methods: In the current study, poly(D,L -lactide) (PLA) nanocarriers loaded with curcumin (CUR) and differing surface charge were evaluated for transport efficacy in combination with electroporation (EP) in dependence on the type of cells. The obtained CUR-loaded nanoparticles with diameters ranging from 195 to 334 nm (derived from dynamic light scattering (DLS)) were characterized by atomic force microscopy (AFM) (morphology and shape) and Doppler electrophoresis (ζ-potential) as well as UV-vis spectroscopy (CUR encapsulation efficiency (about 90%) and photobleaching rate). The drug delivery properties of the obtained PLA nanocarriers enhanced by electroporation were assessed in human colon cancer cells (LoVo), excitable normal rat muscle cells (L6), and free of voltage-gated ion channels cells (CHO-K1). CLSM studies, viability, and ROS release were performed to determine the biological effects of nanocarriers. (3) Results: The highest photodynamic activity indicated anionic nanocarriers (1a) stabilized by C₁₂(COONa)₂ surfactant. Nanocarriers were cytotoxic for LoVo cells and less cytotoxic for normal cells. ROS release increased in cancer cells with the increasing electric field intensity, irradiation, and time after EP. Muscle L6 cells were less sensitive to electric pulses. (4) Conclusions: EP stimulation for CUR-PLA nanocarriers transport was considered to improve the regulated and more effective delivery of nanosystems differing in surface charge.     

The biocompatibility and water uptake behavior of superparamagnetic poly(2-Hydroxyethyl methacrylate) - magnetite nanocomposites as possible nanocarriers for magnetically mediated drug delivery system

The present study aims at formulating a novel multifunctional biocompatible superparamagnetic nanocarriers system comprising of magnetic material in solid polymer matrix of poly (2-hydroxyethyl methacrylate) (PHEMA). To design these nanocarriers PHEMA nanoparticles were prepared by modified suspension polymerization method followed by co-precipitation of iron oxide within the PHEMA matrix. The so prepared superparamagnetic nanocomposite (mPHEMA) was characterized by Fourier transform Infrared spectroscopy (FTIR), and Energy dispersive X-ray spectroscopy (EDAX) confirming the presence of Fe₃O₄ in the PHEMA nanoparticles. The vibrating sample magnetometer (VSM) studies and Mossbauer spectral analysis confirmed the superparamagnetic character of materials having saturation magnetization (Ms) of 23 emu/g at 5 kOe applied magnetic field and room temperature. Biocompatible nature was ascertained by in vitro cytotoxicity test following an extract method based on (ISO10993-5, 2009), anti-haemolytic activity, and bovine serum albumin (blood protein) adsorption test. The water sorption behaviour of superparamagnetic mPHEMA nanocomposites was studied as a function of various factors such as chemical composition of nanoparticles, pH and temperature of the swelling bath, simulated biological fluids and applied magnetic field. The results revealed that the superparamagnetic mPHEMA nanocomposite could prove to be an excellent option for controlled and targeted delivery of anticancer drugs by application of an external magnetic field.     

羧基修饰的超顺磁纳米粒子直接固定化罗伊氏乳杆菌

利用共沉淀法结合高锰酸钾氧化制备所得表面羧基修饰的超顺磁性纳米粒子吸附于罗伊氏乳酸杆菌表面,在磁场协助下实现细胞的固定化。吸附机理分析表明小尺寸相互作用和静电相互作用是磁性纳米粒子与细胞之间的主要作用。分别考察了菌体/磁性粒子质量比、pH、温度、时间等对固定化罗伊氏乳酸杆菌的影响,确定最佳固定条件为菌体与磁性纳米粒子相对质量比为2.25,在pH=3、温度25℃的条件下固定化0.5 h,可实现91%的细胞固定化。最后,对固定化后的细胞进行再培养,与游离细胞相比,两者表现出类似的代谢特征,证实细胞经固定化后仍具有活性。因此,羧基修饰的超顺磁性纳米粒子可成功用于细胞固定化,在不影响细胞活性的情况下,通过磁分离实现细胞的重复利用。     

Controlled delivery of drugs through smart pH-sensitive nanohydrogels for anti-cancer therapies: synthesis,drug release and cellular studies

Nanohydrogels were synthesized by microemulsion polymerization. These nanohydrogels were pre-designed to be pH and temperature stimuli-response materials, using N-isopropylacrilamide as a base monomer and 1-vinyl imidazole as ionizable comonomer. The pH sensitivity was confirmed by measuring the increase or decrease in volume in the nanoparticles by changing the pH of the medium. Nanoparticles were properly characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). Glass-transition temperature increased with vinyl imidazole content, and nanoparticles with average diameter of 68 nm were obtained. Particle size decreases with the increase in pH. After characterization, nanohydrogels were functionalized with folic acid to take advantage that the folate receptor is overexpressed in different types of cancer cells. The nanoparticles were loaded with the drugs: metformin, terfenadine, and 5-fluorouracil. The amount of drug loaded and released by nanoparticles was measured by UV–vis spectroscopy. Then, cellular viability and internalization studies were performed obtaining promising results.     

Preparation of magnetite and tumor dual-targeting hollow polymer microspheres with pH-sensitivity for anticancer drug-carriers

The hollow poly(N,N′-methylenebisacrylamide-co-methacrylic acid) (P(MBAAm-co-MAA)) microspheres were prepared by the selective removal of poly(methacrylic acid) (PMAA) core from the corresponding PMAA/P(MBAAm-co-MAA) core-shell microspheres, which were synthesized via a two-stage distillation precipitation polymerization. The magnetic Fe₃O₄ nanoparticles onto the surface of hollow P(MBAAm-co-MAA) microspheres via partial oxidation of ferrous salt during the chemical deposition in the presence of potassium nitrate as oxidant with the aid of hexamethylene tetramine and the magnetic hollow microspheres were further functionalized with folic acid (FA) via the chemical linkage with amino groups of 3-aminopropyl triethoxysilane (APS)-modified P(MBAAm-co-MAA)@Fe₃O₄ microspheres to afford the magnetite and tumor dual-targeting hollow microspheres. The resultant dual-targeting hollow polymer microspheres with pH-sensitivity were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared-spectrometer (FT-IR), UV-vis absorption spectroscopy, and vibrating sample magnetometer (VSM). Finally, the drug loading capacities of the magnetite and tumor dual-targeting hollow P(MBAAm-co-MAA) microspheres and their releasing dependence on pH values were investigated with doxorubicin hydrochloride (DXR) as an anticancer drug model.     

Incorporating functionalized polyethylene glycol lipids into reprecipitated conjugated polymer nanoparticles for bioconjugation and targeted labeling of cells

We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing.     

Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.