Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery

Gold (Au) nanoparticles (NPs) stabilized with a monolayer of folate-conjugated poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol) copolymer (Au-P(LA-DOX)-b-PEG-OH/FA) was synthesized as a tumor-targeted drug delivery carrier. The Au-P(LA-DOX)-b-PEG-OH/FA NPs consist of an Au core, a hydrophobic poly(l-aspartate-doxorubicin) (P(LA-DOX)) inner shell, and a hydrophilic poly(ethylene glycol) and folate-conjugated poly(ethylene glycol) outer shell (PEG-OH/FA). The anticancer drug, doxorubicin (DOX), was covalently conjugated onto the hydrophobic inner shell by acid-cleavable hydrazone linkage. The DOX loading level was determined to be 17 wt%. The Au-P(LA-DOX)-b-PEG-OH/FA NPs formed stable unimolecular micelles in aqueous solution. The size of the Au-P(LA-DOX)-b-PEG-OH/FA micelles were determined as 24–52 and 10–25 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The conjugated DOX was released from the Au-P(LA-DOX)-b-PEG-OH/FA micelles much more rapidly at pH 5.3 and 6.6 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Cellular uptake of the Au-P(LA-DOX)-b-PEG-OH/FA micelles facilitated by the folate-receptor-mediated endocytosis process was higher than that of the micelles without folate. This was consistent with the higher cytotoxicity observed with the Au-P(LA-DOX)-b-PEG-OH/FA micelles against the 4T1 mouse mammary carcinoma cell line. These results suggest that Au-P(LA-DOX)-b-PEG-OH/FA NPs could be used as a carrier with pH-triggered drug releasing properties for tumor-targeted drug delivery.     

Nanoscale presentation of cell adhesive molecules via block copolymer self-assembly

Precise control over the nanoscale presentation of adhesion molecules and other biological factors represents a new frontier for biomaterials science. Recently, the control of integrin spacing and cellular shape has been shown to affect fundamental biological processes, such as differentiation and apoptosis. Here, we present the self-assembly of maleimide functionalised polystyrene-block-poly (ethylene oxide) copolymers as a simple, yet highly precise method for controlling the position of cellular adhesion molecules. By manipulating the phase separation of the functional PS-PEO block copolymer used in this study, via a simple blending technique, we alter the nanoscale (on PEO domains of 8–14 nm in size) presentation of the adhesion peptide, GRGDS, decreasing lateral spacing from 62 nm to 44 nm and increasing the number density from ～450 to ～900 islands per μm². The results indicate that the spreading of NIH-3T3 fibroblasts increases as the spacing between domains of RGD binding peptides decreases. Further, the same functional PS-PEO surfaces have been utilised to immobilise, via a zinc chelating peptide sequence, poly-histidine tagged proteins and extracellular matrix (ECM) fragments. This method is seen as an ideal platform for investigations into the role of spatial arrangements of cell adhesion molecules and ECM molecules on cell function and, in particular, control of cell phenotype.     

Folate-conjugated amphiphilic block copolymer micelle for targeted and redox-responsive delivery of doxorubicin

In this paper, novel folate-conjugated and redox-responsive crosslinked block copolymer was successfully synthesized for targeted and controlled release of doxorubicin (DOX) to cancer cells. Folate-conjugated poly(ethylene glycol)-b-copolycarbonates (FA-PEG-b-P(MAC-co-DTC)) and methoxy poly(ethylene glycol)-b-copolycarbonates (mPEG-b-P(MAC-co-DTC)) were firstly synthesized by enzymatic method. FA-PEG/mPEG-b-P(MAC-co-DTC)-SS was then obtained by further crosslinking reaction with cystamine. Non-conjugated crosslinked copolymer mPEG-b-P(MAC-co-DTC)-SS- and non-conjugated uncrosslinked copolymer mPEG-b-P(MAC-co-DTC) were also synthesized for comparison. All the amphiphlic copolymers could self-assemble to form nano-sized micelles which dispersed in spherical shape before and after DOX loading. The core crosslinking structure of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS could improve the micellar stability and drug loading capacity, while in vitro release studies also showed more sustained drug release behavior which could be accelerated in reductive condition. Moreover, confocal laser scanning microscopy indicated that the conjugation of FA could enhance the cellular uptake efficiency obviously via FA-receptor-mediated endocytosis, and MTT assays demonstrated highly potent cytotoxic activity of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS.     

Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery

A novel amphiphilic and cationic triblock copolymer consisting of monomethoxy poly(ethylene glycol), poly(varepsilon-caprolactone) (PCL) and poly(2-aminoethyl ethylene phosphate) denoted as mPEG(45)-b-PCL(100)-b-PPEEA(12) was designed and synthesized for siRNA delivery. The copolymers were well characterized by (1)H NMR spectroscopy and gel permeation chromatography. Micelle nanoparticles' (MNPs) formation of this amphiphilic copolymer in aqueous solution was studied by dynamic light scattering, transmission electron microscopy and fluorescence technique. MNPs took uniform spherical morphology with zeta potential of around 45mV and were stabilized by hydrophobic-hydrophobic interaction in the PCL core, exhibiting the critical micelle concentration at 2.7x10(-3)mg/mL. Such MNPs allowed siRNA loading post nanoparticle formation without change in uniformity. The average diameter of nanoparticles after siRNA binding ranged from 98 to 125nm depending on N/P ratios. The siRNA loaded nanoparticles can be effectively internalized and subsequently release siRNA in HEK293 cells, resulting in significant gene knockdown activities, which was demonstrated by delivering two siRNAs targeting green fluorescence protein (GFP). It effectively silenced GFP expression in 40-70% GFP-expressed HEK293 cells and it was observed that higher N/P ratio resulted in more effective silence which was likely due to better cell internalization at higher N/P ratio. MTT assay demonstrated that neither MNPs themselves nor siRNA loaded MNPs showed cytotoxicity even at high concentrations. Such cationic MNPs made from biocompatible and biodegradable polymers are promising for siRNA delivery.     

Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery

Folate-conjugated unimolecular micelles based on amphiphilic hyperbranched block copolymer, Boltorn^® H40-poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol)/FA-conjugated poly(ethylene glycol) (H40-P(LA-DOX)-b-PEG-OH/FA), were synthesized as a carrier for tumor-targeted drug delivery. The anticancer drug DOX was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms by pH-sensitive hydrazone linkage. The size of the unimolecular micelles was determined as 17–36 and 10–20 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The release profiles of the DOX from the H40-P(LA-DOX)-b-PEG-OH/FA micelles showed a strong dependence on the environmental pH values. The DOX release rate increased in the acidic medium due to the acid-cleavable hydrazone linkage between the DOX and micelles. Cellular uptake of the H40-P(LA-DOX)-b-PEG-OH/FA micelles was found to be higher than that of the H40-P(LA-DOX)-b-PEG-OH micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. Degradation studies showed that the H40-P(LA-DOX)-b-PEG-OH/FA copolymer hydrolytically degraded into polymer fragments within six weeks. These results suggest that H40-P(LA-DOX)-b-PEG-OH/FA micelles could be a promising nanocarrier with excellent in vivo stability for targeting the drugs to cancer cells and releasing the drug molecules inside the cells by sensing the acidic environment of the endosomal compartments.     

Self-assembled pH-responsive MPEG-b-(PLA-co-PAE) block copolymer micelles for anticancer drug delivery

A series of amphiphilic pH-responsive poly (ethylene glycol) methyl ether-b-(poly lactic acid-co-poly (β-amino esters)) (MPEG-b-(PLA-co-PAE)) block copolymers with different PLA/PAE ratios were designed and synthesized via a Michael-type step polymerization. The molecular structures of the copolymers were confirmed with (1)H NMR and gel permeation chromatography (GPC). These amphiphilic copolymers were shown to self-assemble into core/shell micelles in aqueous solution at low concentrations, and their critical micelle concentrations (CMC) in water were 1.2-9.5 mg/L. The pH-responsive PAE segment was insoluble at pH 7.4, but it became positively charged and soluble via protonation of amino groups at pH lower than 6.5. The average particle size and zeta potential of micelles increased from 180 nm and 15 mV to 220 nm and 40 mV, respectively, when the pH decreased from 7.4 to 5.0. Doxorubicin (DOX) was loaded into the core of these micelles with a high drug loading of 18%. The in vitro DOX release from the micelles was significantly accelerated when solution pH decreased from 7.4 to 5.0. DOX release in the first 10 h appeared to follow Fickian diffusion mechanism. Toxicity test showed that the copolymers had low toxicity whereas the DOX-loaded micelles remained high cytotoxicity for HepG2 cells. The results indicate the pH-sensitive MPEG-b-(PLA-co-PAE) micelle may be a potential hydrophobic drug delivery carrier for cancer targeting therapy with sustained release.     

Biotinylated thermoresponsive micelle self-assembled from double-hydrophilic block copolymer for drug delivery and tumor target

A multifunctional micellar drug carrier formed by the thermosensitive and biotinylated double-hydrophilic block copolymer (DHBC), biotin-poly(ethylene glycol)-block-poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide) (biotin-PEG-b-P(NIPAAm-co-HMAAm)), was designed and prepared. The P(NIPAAm-co-HMAAm) block with an molar feed ratio of NIPAAm and HMAAm (10:1) was identified to exhibit the reversible phase transition at the lower critical solution temperature (LCST) of 36.7 degrees C. Cytotoxicity study indicated that the biotin-PEG-b-P(NIPAAm-co-HMAAm) copolymer did not exhibit obvious cytotoxicity. The block copolymer was capable of self-assembling into micelle in water. Transmission electron microscopy showed that the self-assembled micelles were regularly spherical in shape. The anticancer drug methotrexate (MTX) was loaded in the micelles and the in vitro release behaviors of MTX at different temperatures were investigated. The association of biotin molecule with the copolymer was confirmed by a unique capillary electrophoresis immunoassay (CEIA) method based on enhanced chemiluminescence (CL) detection. The fluorescence spectroscopy analysis as well as confocal microscopy studies confirmed the DHBC drug carriers could specifically and efficiently bind to cancer cells with pretreatment of biotin-transferrin, suggesting that the multifunctionalized DHBC micelle may be a useful drug carrier for tumor targeting.     

Synthesis and assembly of novel chitin derivatives having amphiphilic polyoxazoline block copolymer as a side chain

The first synthesis of chitin derivatives with well-defined block copolymer side chains, i. e., chitin-graft-[poly(2-methyl-2-oxazoline)-block-poly(2-phenyl-2-oxazoline)] ( 5 ), chitin-graft-[poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)] ( 6 ), and chitin-graft-[poly(2-methyl-2-oxazoline)-block-poly(2-tert-butyl-2-oxazoline)] ( 7 ), was achieved by the reaction of partially deacetylated chitin ( 1 ) with living polyoxazoline block copolymers 2 – 4 . The graft copolymers 5 – 7 are associated into micelles above the critical micelle concentration (CMC). CMCs of 5 (0.01–0.02 wt.-%) are smaller than those (0.32–0.50 wt.-%) of ω-hydroxyl-terminated poly(2-phenyl-2-oxazoline)-block-poly(2-methyl-2-oxazoline) ( 2 -OH), which is a model block copolymer of the side chain segment of 5 . The self-aggregates of 5 – 7 are capable of forming a complex with hydrophobic low molecular weight substances such as pyrene and magnesium 1-anilinonaphthalene-8-sulfonate (ANS). Cryo-transmission electron microscopy showed that the graft copolymer 5 forms globular particles (diameter: 40 nm) and larger cylindrical aggregates (diameter: 40 nm, length: 80–200 nm). The average radius of gyration of the particles of 5 from the SANS analysis is 36 nm.     

Bio-functional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs

In this study, a block copolymer, poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-2-aminoethyl methacrylate)-b-poly(10-undecenoic acid) (P(NIPAAm-co-DMAAm-co-AMA)-b-PUA) was synthesized, and folic acid was conjugated to the hydrophilic block through the amine group in AMA. This polymer was self-assembled into micelles, which exhibited pH-induced temperature sensitivity. They were smaller in size, and possessed a better-defined core-shell structure as well as more stable hydrophobic core than the random copolymer P(NIPAAm-co-DMAAm-co-UA), and provided a shell with folate molecules. An anti-cancer drug, doxorubicin (DOX) was encapsulated into the micelles. The mean diameter of the blank and DOX-loaded micelles was less than 100 nm. DOX release was pH-dependent, being faster at low pH (endosomes/lysosomes). Therefore, DOX was readily released from the micelles into the nucleus after being taken up. More importantly, IC50 of DOX-loaded micelles with folate against folate receptor-expressing 4T1 and KB cells was much lower than that of the DOX-loaded micelles without folate (3.8 vs. 7.6 mg/L for 4T1 cells and 1.2 vs. 3.0mg/L for KB cells). In vivo experiments conducted in a 4T1 mouse breast cancer model demonstrated that DOX-loaded micelles had a longer blood circulation time than free DOX (t(1/2): 30 min and 140 min, respectively). In addition, the micelles delivered an increased amount of DOX to the tumor when compared to free DOX. These bio-functional micelles may make a promising carrier to transport anticancer drugs specifically to tumor cells and release the drug molecules inside the cells to the cytosols for improved chemotherapy.     

Gene delivery via DNA incorporation within a biomimetic apatite coating

Integrating inductivity with conductivity in a material may advance tissue engineering. An organic/inorganic hybrid was developed by incorporating plasmid DNA encoding for the β-gal gene complexed with Lipofectamine 2000^® (DNA–Lipoplex) within apatite via coprecipitation. It was hypothesized that this system will result in enhanced transfection efficiency compared to DNA–Lipoplexes adsorbed to the mineral surface and DNA coprecipitated without Lipofectamine 2000^®. PLGA films were cast onto glass slips and apatite and DNA were coprecipitated in modified simulated body fluid (mSBF). DNA–Lipoplex presence in mineral, DNA–Lipoplex stability (vs. coprecipitation time), and transfection efficiency (determined with C3H10T1/2 cells) as a function of coprecipitation time, DNA–Lipoplex concentration, and DNA incorporation method were studied. DNA–Lipoplex presence and spatial distribution on apatite were confirmed through fluorescence. Transfection efficiency was highest for 6 h of DNA–Lipoplex coprecipitation. Differences in transfection efficiency were found between the DNA concentrations, with the highest efficiency for coprecipitation being 40 μg/ml (p ≤ 0.009 relative to other coprecipitation concentrations). Significant differences in transfection efficiency existed between incorporation methods (p < 0.05) with the highest efficiency for DNA–Lipoplex coprecipitation. This hybrid material system not only integrates inductivity provided by the DNA and conductivity provided by the apatite, but it also has significant implications in non-viral gene delivery due to its ability to increase transfection efficiency.     

Self-assembled, thermosensitive micelles of a star block copolymer based on PMMA and PNIPAAm for controlled drug delivery

A four-arm star block copolymer, comprised of a hydrophobic PMMA arm and an average of three hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms were designed and synthesized from the molecular level. The amphiphilic star block copolymer is capable of self-assembling into micelles in water, which was confirmed by FT-IR, (1)H NMR and fluorescence spectroscopy. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 34 degrees C, observed by optical absorbance measurements. Resulted polymeric micelles loaded with prednisone acetate showed a much improved drug release behavior due to the special micellar structure.     

多西他赛共聚物纳米胶束的制备及性能研究

目的制备一种包载多西他赛的聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸(PLGA-PEG-PLGA)三嵌段共聚物纳米胶束,并考察其相关性能。方法采用开环聚合法合成共聚物,直接溶解法制备载多西他赛共聚物纳米胶束,荧光光谱法测定临界胶束浓度,高效液相色谱检测载药胶束的包封率与载药率,透析法测定载药胶束体外释放情况,扫描电镜观察纳米胶束的形态,激光粒径仪测量共聚物纳米胶束粒径及分布,改良寇氏法测定载药胶束的半数致死量。结果直接溶解法制备的共聚物纳米胶束的临界胶束浓度为4.5×10-3 g/L,多西他赛与共聚物投料比为1∶20制备的载多西他赛共聚物纳米胶束的包封率为98.20%,载药率达4.68%,在体外平稳释放时间约3 d。扫描电子显微镜观察载多西他赛共聚物纳米胶束呈类圆形,分散良好,平均粒径为30.8 nm,多元分散系数0.42。载多西他赛共聚物纳米胶束静脉注射小鼠的半数致死量为273.5 mg/kg。结论采用直接溶解法可制备一种载多西他赛的PLGA-PEG-PLGA三嵌段共聚物纳米胶束,包封率高,体外释药平稳,毒副作用小,具有潜在的临床应用价值。     

Hydrazone self-crosslinking of multiphase elastin-like block copolymer networks

Biosynthetic strategies for the production of recombinant elastin-like protein (ELP) triblock copolymers have resulted in elastomeric protein hydrogels, formed through rapid physical crosslinking upon warming of concentrated solutions. However, the strength of physically crosslinked networks can be limited, and options for non-toxic chemical crosslinking of these networks are not optimal. In this report, we modify two recombinant elastin-like proteins with aldehyde and hydrazide functionalities. When combined, these modified recombinant proteins self-crosslink through hydrazone bonding without requiring initiators or producing by-products. Crosslinked materials are evaluated for water content and swelling upon hydration, and subject to tensile and compressive mechanical tests. Hydrazone crosslinking is a viable method for increasing the mechanical strength of elastin-like protein polymers, in a manner that is likely to lend itself to the biocompatible in situ formation of chemically and physically crosslinked ELP hydrogels.     

A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA

Recent advances in efficient microRNA (miRNA) delivery techniques using brain-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated neurological diseases. Here, we report the rabies virus glycoprotein (RVG)-labeled non-toxic SSPEI nanomaterials capable of neuron-specific miR-124a delivery to neuron in vivo. The RVG-labeled BPEI-SS (RVG-SSPEI) nanocarrier showed less toxicity in acetylcholine receptor-positive Neuro2a cells, and electrostatic interaction of RVG-SSPEI with miR-124a exhibited optimal transfection efficacy. The RVG-SSPEI polymer specifically targeted Neuro2a using cy5.5-miR-124a mixed with RVG-SSPEI. The functional action of miR-124a oligomers released from polyplexes in the cytoplasmic region was evaluated by a reporter vector containing a miR-124a -binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. Cy5.5-miR-124a/RVG-SSPEI- injected into mice via tail veins displayed the enhanced accumulation of miR-124a in the isolated brain. Hindrance of the efficient penetration of neuronal cells by size limitation of the miR-124a/RVG-SSPEI improved with the help of mannitol through blood-brain barrier disruption. These findings indicated that the RVG peptide combined with mannitol infusion using SSPEI polymer for neuron-specific targeting in vivo is sufficient to deliver neurogenic microRNA into the brain.     

Gene transfection of hyperbranched PEI grafted by hydrophobic amino acid segment PBLG

The complex copolymer of hyperbranched polyethylenimine (PEI) with hydrophobic poly(gamma-benzyl L-glutamate) segment (PBLG) at their chain ends was synthesized. This water-soluble copolymer PEI-PBLG (PP) was characterized for DNA complexation (gel retardation assay, particle size, DNA release and DNase I protection), cell viability and in vitro transfection efficiency. The experiments showed that PP can effectively condense pDNA into particles. Size measurement of the complexes particles indicated that PP/DNA tended to form smaller nanoparticles than those of PEI/DNA, which was caused by the hydrophobic PBLG segments compressing the PP/DNA complex particles in aqueous solution. The representative average size of PP/DNA complex prepared using plasmid DNA (pEGFP-N1, pDNA) was about 96 nm. The condensed pDNA in the PP/pDNA complexes was significantly protected from enzymatic degradation by DNase I. Cytotoxicity studies by MTT colorimetric assays suggested that the PP had much lower toxicity than PEI. The in vitro transfection efficiency of PP/pDNA complexes improved a lot in HeLa cells, Vero cells and 293T cells as compared to that of PEI-25K by the expression of Green Fluorescent Protein (GFP) as determined by flow cytometry. Thus, the water-soluble PP copolymer showed considerable potential as carriers for gene delivery.     

Sedimentation and light scattering study of block copolymer association

Dilute solutions of a three-block styrene-butadiene-styrene copolymer in the mixed selective solvent tetrahydrofuran/allyl alcohol exhibit a more or less pronounced turbidity. Sedimentation analysis and light scattering reveal that these solutions contain two components, namely, a molecularly dissolved copolymer (unimer) and rather compact supermolecular aggregates (micelles) with a relatively narrow molecular weight distribution. The unimer/micelles weight ratio and the weight of micelles were determined as a function of the composition of the mixed solvent, temperature, and copolymer concentration.     

Thermal properties of an ethylene/1-butene block copolymer

A precision, adiabatic vacuum calorimeter and a differential scanning calorimeter have been used to measure the heat capacity of an ethylene/1-butene block copolymer over the temperature range 80–450°K. An estimate has been made of heat capacity values below 80°K. Values of the heat capacity, entropy, enthalpy, and free energy are listed at 10°K intervals. A glass transition (200°K), a transition of unknown origin (335°K) and a melting transition (400°K) were observed.     

Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections

Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.     

Click assembly of magnetic nanovectors for gene delivery

Functionalization of iron oxide nanoparticles with quaternary ammonium ion-based aminooxy and oxime ether substrates provides a flexible route for generating magnetic gene delivery vectors. Using the MCF-7 breast cancer cell line, our findings show that pDNA magnetoplexes derived from the lipid-coated nanoparticle formulation dMLP transfect in the presence of 10% serum with or without magnetic assistance at significantly higher levels than a commonly used cationic liposome formulation, based on luciferase assay. The present ion-pairing, click chemistry approach furnishes Fe(3)O(4) nanoparticles with lipid layers. The resultant magnetic nanovectors serve as transfection enhancers for otherwise transfection-inactive materials.