Combining segmental bulk- and single-cell RNA-sequencing to define the chondrocyte gene expression signature in the murine knee joint.

OBJECTIVE: Due to the small size of the murine knee joint, extracting the chondrocyte transcriptome from articular cartilage (AC) is a major technical challenge. In this study, we demonstrate a new pragmatic approach of combining bulk RNA-sequencing (RNA-seq) and single cell (sc)RNA-seq to address this problem. DESIGN: We propose a new cutting strategy for the murine femur which produces three segments with a predictable mixed cell population, where one segment contains AC and growth plate (GP) chondrocytes, another GP chondrocytes, and the last segment only bone and bone marrow. We analysed the bulk RNA-seq of the different segments to find distinct genes between the segments. The segment containing AC chondrocytes was digested and analysed via scRNA-seq. RESULTS: Differential expression analysis using bulk RNA-seq identified 350 candidate chondrocyte gene in the AC segment. Gene set enrichment analysis of these genes revealed biological processes related- and non-related to chondrocytes, including, cartilage development (adj. P-value: 3.45E-17) and endochondral bone growth (adj. P-value 1.22E-4), respectively. ScRNA-seq of the AC segment found a cluster of 131 cells containing mainly chondrocytes. This cluster had 759 differentially expressed genes which enriched for extracellular matrix organisation (adj. P-value 7.76E-40) and other joint development processes. The intersection of the gene sets of bulk- and scRNA-seq contained 75 genes. CONCLUSIONS: Based on our results, we conclude that the combination of the two RNA-seq methods is necessary to precisely delineate the chondrocyte transcriptome and to study the disease phenotypes of chondrocytes in murine OA models in the future.

Pain and knee damage in male and female mice in the medial meniscal transection-induced osteoarthritis.

OBJECTIVE: To investigate sex effects on pain-related behaviors in the medial meniscal transection (MMT) knee osteoarthritis (OA) model. METHODS: Experiments were performed in male and female C57BL/6J mice (12/group/sex). MMT was induced by transection of the medial collateral ligament and the medial meniscus. Sham-operated and naïve mice served as controls. Mechanical and heat sensitivity in hind paws, hind limb use, and locomotor activity were measured for 3 months. Knee histology was performed on week 12. RESULTS: In males, MMT triggered a bi-phasic mechanical hypersensitivity and decreased load on OA limb, with an acute post-operative (1-5 days) and chronic (3-12 weeks) OA phases separated by a remission in the intermediate phase (1-2 weeks). Females showed a less pronounced bi-phasic pattern, with a greater mechanical hypersensitivity, but not poorer limb use, than males in the intermediate phase (maximal difference: 1.1 g, 95% confidence intervals (CI) [0.7, 1.5]). There were no major sex differences in the chronic phase. MMT did not induce heat hypersensitivity or change in locomotor activity in the chronic phase in both sexes. MMT caused more severe cartilage damage in males than in females (maximal difference: 1.1 score points, 95% CI [1.9, 0.3]), and a comparable between sexes osteophyte formation. The knee damage did not correlate with pain. CONCLUSIONS: MMT modelled human knee OA well, capturing cartilage destruction and osteophyte formation, mechanical pain, and poorer limb use in both sexes. Sex differences in pain were modality- and time-dependent, reflecting complex sex-related features of human OA.

Synthesis, characterisation, cellular uptake and cytotoxicity of functionalised magnetic ruthenium (II) polypyridine complex core-shell nanocomposite.

The development of multifunctional nanoparticles comprising of a magnetic core in conjunction with appropriate molecules with capabilities to impart functionalities like luminescent, specific binding sites to facilitate attachment of moieties. This has attracted increasing attention and enables identification of promising candidates using for applications such as diagnostics and cure through early detection and localized delivery. Many studies have been performed on the synthesis and cellular interactions of core-shell nanoparticles, in which a functional inorganic core is coated with a biocompatible polymer layer that should reduce nonspecific uptake and cytotoxicity Here we report the synthesis and characterisation of multifunctional core-shell magnetic, luminescent nanocomposite (Fe3O4@SiO2@[Ru(Phen)3]2+@SiO2@NH2). Fe3O4 as core and a luminescent ruthenium (II) complex encapsulated with silica shell, and then it is functionalized by an amine group by APTMS. The magnetic, luminescent, and biological activity of this multifunctional nanocomposite have also been studied to prove the nanocomposite is biocompatible, cellular uptake. The synthesized nanocomposite was completely characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and emission spectroscopy. MTT assay and cellular uptake by flow cytometry results proved that magnetic ruthenium (II) polypyridine complex - core shell nanocomposite has biocompatibility, minimum cytotoxicity and internalized inside B16F10 cells and confirms the potential biomedical applications.

Multiscale Systems-Pharmacology Pipeline to Assess the Prophylactic Efficacy of NRTIs Against HIV-1.

While HIV-1 continues to spread, the use of antivirals in preexposure prophylaxis (PrEP) has recently been suggested. Here we present a modular systems pharmacology modeling pipeline, predicting PrEP efficacy of nucleotide reverse transcriptase inhibitors (NRTIs) at the scale of reverse transcription, target-cell, and systemic infection and after repeated viral exposures, akin to clinical trials. We use this pipeline to benchmark the prophylactic efficacy of all currently approved NRTIs in wildtype and mutant viruses. By integrating pharmacokinetic models, we find that intracellular tenofovir-diphosphate builds up too slowly to halt infection when taken "on demand" and that lamivudine may substitute emtricitabine in PrEP combinations. Lastly, we delineate factors confounding clinical PrEP efficacy estimates and provide a method to overcome these. The presented framework is useful to screen and optimize PrEP candidates and strategies and to understand their clinical efficacy by integrating the diverse scales which determine PrEP efficacy.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Hierarchical mesoporous In2O3 with enhanced CO sensing and photocatalytic performance: distinct morphologies of In(OH)3 via self assembly coupled in situ solid-solid transformation.

The present investigation details our interesting findings and insights into the evolution of exotic hierarchical superstructures of In(OH)3 under solvothermal conditions. Controlled variation of reaction parameters such as, reactant concentration, solvent system, crystal structure modifiers, water content along with temperature and time, yielded remarkable architectures. Diverse morphologies achieved for the first time includes (i) raspberry-like hollow spheres, (ii) nanosheet-assembled spheres, (iii) nanoparticle-assembled spheres, (iv) nanocube-assembled hollow spheres, (v) yolk-like spheres, (vi) solid spheres, (vii) nanosheets/flakes, and (viii) ultrafine nanosheets. A plausible mechanism is proposed based on the evidence gathered from a comprehensive analysis aided by electron microscopy and X-ray diffraction studies. Key stages of morphological evolution could be discerned and rationally correlated with nucleation, growth, oriented attachment, and Ostwald ripening mediated by dissolution-redeposition mechanism coupled with solid evacuation. Remarkably phase-pure bcc-In2O3 with retention of precursor morphology could be realized postcalcination at 400 °C, which underlines the advantage of this strategy. Two typical hierarchical structures (raspberry-like hollow spheres and nanoparticles assembled spheres) were investigated for their gas sensing and photocatalytic performances to highlight the advantages offered by nanostructuring. An impressive sensor response, Smax ≈ 7340 and 4055, respectively for the two structures along with appreciably fast response/recovery times over a wide concentration range and as low as 1 ppm exhibits the superior sensitivity toward carbon monoxide (CO). When compared to commercial In2O3, estimated rate constant indicates ∼3-4 times enhancement in photocatalytic activity of the substrates toward Rhodamine-B.

Targeted in vivo photodynamic therapy with epidermal growth factor receptor-specific peptide linked nanoparticles.

In targeted photodynamic therapy (tPDT), photosensitizers (PS) are targeted to disease tissue to reduce the dosage of PS and in addition to reduce the photo damage to the non-target tissue. We synthesized iron oxide nanoparticles (NP) armored with tumor targeting peptide and PS for targeted PDT. Chitosan covered Fe3O4 NPs (30 nm) were deposited with gold NPs to generate two distinct chemical surfaces. To the gold particles PS was attached with a lipoic acid linker. Human epidermal growth factor receptor (hEGFR)-specific peptide was also attached to the same particles via a nickel-nitrilotriacetic acid linker attached to the chitosan. Using these nanoparticles, peptide specific uptake and PDT mediated cell death of the SK-OV-3 cells (Her2(+) positive cells) were demonstrated by confocal microscopy, T2 imaging and viability assays. Peptide mediated preferential distribution of these NPs into tumor tissue was also shown in a xenograft tumor model. After one intravenous injection and one PDT dose, peptide bound NPs retarded tumor growth significantly compared to dark controls or treatments with NPs without peptide. The tumor retardation by targeted NPs was achieved at a PS concentration of 3.9 nmol/animal, whereas similar effect was seen with free PS at 220 nmol/animal. Therapeutic potential of these peptide containing NPs would be a useful in targeted PDT and in imaging the target tissue.

Structure and Li+ dynamics of Sb-doped Li7La3Zr2O12 fast lithium ion conductors.

Antimony-doped lithium stuffed garnets Li(7-x)La3Zr(2-x)Sb(x)O12 (x = 0.2-1.0) prepared using a conventional solid state reaction method are characterized using Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Energy Dispersive Analysis by X-ray (EDAX), AC Impedance spectroscopy, Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) and Raman spectroscopic techniques. PXRD confirms the formation of a garnet-like structure with cubic symmetry for the entire selected compositional range. Among the investigated compounds, the compound with an Sb content corresponding to x = 0.4, i.e. Li6.6La3Zr1.6Sb0.4O12 exhibits the maximum total (bulk + grain boundary) ionic conductivity of 7.7 × 10(-4) S cm(-1) at 30 °C. The shape of the imaginary part of the modulus spectra suggests that the relaxation processes are non-Debye in nature. The full width at half maximum (FWHM) for the master modulus curve of Li6.6La3Zr1.6Sb0.4O12 is found to be the smallest among the investigated lithium garnets. The full width at half maximum (FWHM) of the (7)Li MAS NMR spectrum for the composition Li6.6La3Zr1.6Sb0.4O12 is the smallest among the investigated compounds. Raman data collected for the compounds in this series indicates an increase of Li(+) occupancy in the tetrahedrally coordinated site with an associated decrease of Li(+) occupancy in the octahedrally coordinated site during an increase of x in Li(7-x)La3Zr(2-x)Sb(x)O12. The present investigation reveals that the optimal Li(+) concentration required to achieve the maximum room-temperature Li(+) conductivity in Li(7-x)La3Zr(2-x)Sb(x)O12 lithium stuffed garnet is around x = 0.4.

A facile and green approach for the controlled synthesis of porous SnO2 nanospheres: application as an efficient photocatalyst and an excellent gas sensing material.

A facile and elegant methodology invoking the principles of Green Chemistry for the synthesis of porous tin dioxide nanospheres has been described. The low-temperature (∼50 °C) synthesis of SnO2 nanoparticles and their self-assembly into organized, uniform, and monodispersed porous nanospheres with high surface area is facilitated by controlling the concentration of glucose, which acts as a stabilizing as well as structure-directing agent. A systematic control on the stannate to glucose molar concentration ratio determines the exact conditions to obtain monodispersed nanospheres, preferentially over random aggregation. Detailed characterization of the structure, morphology, and chemical composition reveals that the synthesized material, 50 nm SnO2 porous nanospheres possess BET surface area of about 160 m²/g. Each porous nanosphere consists of a few hundred nanoparticles ∼2-3 nm in diameter with tetragonal cassiterite crystal structure. The SnO2 nanospheres exhibit elevated photocatalytic activity toward methyl orange with good recyclability. Because of the high activity and stability of this photocatalyst, the material is ideal for applications in environmental remediation. Moreover, SnO2 nanospheres display excellent gas sensing capabilities toward hydrogen. Surface modification of the nanospheres with Pd transforms this sensing material into a highly sensitive and selective room-temperature hydrogen sensor.

Self-assembly of short peptides composed of only aliphatic amino acids and a combination of aromatic and aliphatic amino acids.

The morphology of structures formed by the self-assembly of short N-terminal t-butyloxycarbonyl (Boc) and C-terminal methyl ester (OMe) protected and Boc-deprotected hydrophobic peptide esters was investigated. We have observed that Boc-protected peptide esters composed of either only aliphatic hydrophobic amino acids or aliphatic hydrophobic amino acids in combination with aromatic amino acids, formed highly organized structures, when dried from methanol solutions. Transmission and scanning electron microscopic images of the peptides Boc-Ile-Ile-OMe, Boc-Phe-Phe-Phe-Ile-Ile-OMe and Boc-Trp-Ile-Ile-OMe showed nanotubular structures. Removal of the Boc group resulted in disruption of the ability to form tubular structures though spherical aggregates were formed. Both Boc-Leu-Ile-Ile-OMe and H-Leu-Ile-Ile-OMe formed only spherical nanostructures. Dynamic light scattering studies showed that aggregates of varying dimensions were present in solution suggesting that self-assembly into ordered structures is facilitated by aggregation in solution. Fourier transform infrared spectroscopy and circular dichroism spectroscopy data show that although all four of the protected peptides adopt well-defined tertiary structures, upon removal of the Boc group, only H-Phe-Phe-Phe-Ile-Ile-OMe had the ability to adopt ß-structure. Our results indicate that hydrophobic interaction is a very important determinant for self-assembly and presence of charged and aromatic amino acids in a peptide is not necessary for self-assembly.

Viable method for the synthesis of biphasic TiO2 nanocrystals with tunable phase composition and enabled visible-light photocatalytic performance.

Here we demonstrate a facile method to synthesize high-surface-area TiO(2) nanoparticles in aqueous-ethanol system with tunable brookite/rutile and brookite/anatase ratio possessing high surface area that exhibits enhanced photoactivity. Titanium tetrachloride (TiCl(4)) is used as the metal precursor of choice and the tuning of phase compositions are achieved by varying the water:ethanol ratio, used as mixed solvent system. The synthesized samples were characterized in detail using X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), BET nitrogen sorption measurements, and UV-vis diffuse reflectance spectroscopy (UV-DRS). The photocatalytic activity of biphasic TiO(2) nanocrystals was evaluated by following the degradation kinetics of rhodamine-B dye in aqueous solution and under visible light. Mixed-phase TiO(2) nanostructures composing 83% brookite and 17% of rutile exhibited superior photoactivity when compared to Degussa P25 and phase-pure anatase nanocrystals. The exceptional photocatalytic activity of the synthesized nanostructures can be elucidated on the account of their large surface area and biphasic composition. On the basis of the detailed investigation reported herein, we conclude that tuning the ethanol volume in the mixed-solvent reaction system holds the key to tailor and control the final TiO(2) phase obtained.

Morphology-controlled assembly of ZnO nanostructures: a bioinspired method and visible luminescence.

In a bioinspired methodology, positively charged polypeptides and polyamines directly catalyse ZnO mineralization under "green" conditions of room temperature and neutral pH. The polyamines not only act as mineralizing agents for the formation of ZnO nanoparticles, but also self-assemble the nanoparticles to form spindle-like morphologies at these very ambient conditions. Both the directional growth of ZnO and its luminescent property have a pH dependency. At higher pH, the ZnO shape changes to a rodlike morphology that exhibits green photoluminescence with different intensity than that for ZnO spindles.

Pd on surface-modified NiFe2O4 nanoparticles: a magnetically recoverable catalyst for Suzuki and Heck reactions.

This communication reports on the use of NiFe2O4-DA-Pd, a complete magnetically separable catalyst for Suzuki and Heck coupling reactions of aromatic halide derivatives. The catalyst efficiency for the coupling of chloro derivatives is as good as bromo and iodo derivatives. Catalytic efficiency remains unaltered even after three repeated cycles.

Pd on amine-terminated ferrite nanoparticles: a complete magnetically recoverable facile catalyst for hydrogenation reactions.

[structure: see text]. The present communication reports a facile route for Pd(0) immobilization on the surface of amine-terminated Fe3O4 and NiFe2O4 nanoparticles for a series of hydrogenation reactions. The catalysts are completely recoverable with the simple application of an external magnetic field, and the efficiency of the catalyst remains unaltered even after 10 repeated cycles for each of the reactions.

Water-soluble nanoparticles from random copolymer and oppositely charged surfactant, 3a. Nanoparticles of poly(ethylene glycol)-based cationic random copolymer and fatty acid salts.

In this report, we investigate the nanoparticle formation between random copolymers (RCPs) of methoxy-poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) and oppositely charged natural surfactants, sodium oleate and sodium laurate, using turbidimetric titration, steady-state fluorescence, dynamic light scattering, and electron microscopy. Though sodium oleate and sodium laurate are sparingly soluble in water, the nanoparticle complexes formed between the RCPs and these surfactants are soluble in the entire range of compositions studied here, including the stoichiometric electronetural complexes. The spherical nature of these nanoparticle complexes is revealed by electron microscopic (EM) analysis. Dynamic light scattering (DLS) showed that the average diameters of the nanoparticles are in the range 50 to 150 nm, which is supported by EM analysis. Pyrene fluorescence experiments suggested that these soluble nanoparticles have hydrophobic cores, which may solubilize hydrophobic drug molecules. The polarity index (I(1)/I(3)) obtained from the pyrene fluorescence spectra and the conductometric measurements showed that the critical concentration of fatty acid salts needed to obtain nanoparticles are in the order of 10(-4) M. Further, the complexation of such poorly water-soluble amphiphilic surfactants with polymers offers a useful method for the immobilization of hydrophobic compounds towards water-soluble drug carrier formulations. The formation of water-soluble nanoparticles by the self-assembly of fatty acid salts upon interacting with oppositely charged poly(ethylene glycol)-based polyions.

Investigations on the mechanisms of ionic conductivity in PEO-PU/PAN semi-interpenetrating polymer network-salt complex polymer electrolytes: an impedance spectroscopy study.

This paper is a first comprehensive study on the correlated ion transport mechanisms contributing to the overall conductivity behavior in a new class of poly(ethylene oxide)-polyurethane/polyacrylonitrile (PEO-PU/PAN) semi-interpenetrating polymer networks (semi-IPNs)-salt complex polymer electrolytes. A simultaneous investigation of the electrical response on PEO-PU/PAN/LiClO(4) and PEO-PU/PAN/LiCF(3)SO(3) semi-IPNs with varying EO/Li mole ratios (100, 60, 30, 20, 15, 10) has been carried out by impedance spectroscopy. Analysis of the complex plane and spectroscopic plots indicated the presence of two microscopic phases corresponding to the PEO-PU and PAN domains, which leads to space charge polarization in these systems. A suitably modified approach based on the universal power law (UPL) considering the independent contribution from the individual microphases of semi-IPNs facilitates a complete interpretation of the spectroscopic profiles for the real component of conductivity (sigma'(omega)). The sigma'(omega) spectroscopic profiles were fitted with two power law equations, where the frequency region up to approximately 300 kHz is the conductivity profile associated with the PAN phase and beyond this is the superimposed contribution of the PEO-PU phase. Simulated fits using the UPL equation revealed two relaxation times (tau(PEO)(-)(PU), tau(PAN)) related to ionic hopping in the PEO-PU and PAN phases in addition to the conductivity relaxation time (tau(peak)) determined from the Debye peaks. The respective power law exponents (n(PEO)(-)(PU) approximately 0.5-0.8, n(PAN) approximately 1.0-1.6) indicate that though cationic hopping in the softer PEO-PU phase is favored, anionic hopping in the PAN phase contributes significantly to the charge transport processes in these semi-IPNs. Correlation of the experimental results with the simulated fits enable us to distinguish the effects of semi-IPN composition, temperature, morphology, ion-ion, and ion-polymer interactions, which influence the microscopic molecular events, involved in the charge transport in these complex semi-IPN polymer electrolytes.

Water-soluble complexes from random copolymer and oppositely charged surfactant. 2. Complexes of poly(ethylene glycol)-based cationic random copolymer and bile salts.

The complexes formed between the positively charged random copolymers (RCPs) of methoxy-poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) with oppositely charged biosurfactants (bile salts) were studied using turbidimetric titration, steady-state fluorescence, dynamic light scattering, and electron microscopy. Studies showed that the complexes of the RCPs of MAPTAC and MePEGMA with less than 68 mol % of PEG content precipitate in water, whereas the complexes of the copolymer with 89 and 94 mol % of PEG content do not precipitate in the entire range of composition of the mixture including stoichiometric compositions when the electroneutral complexes are formed. The complexes with true hydrophobic domains, which are a prerequisite characteristic to serve as a carrier, can be obtained at much lower concentration than the critical micelle concentration of the corresponding surfactant. For a particular surfactant, hydrophobic domains are obtained at lower Z-/+ for the random copolymer with lower PEG content. The hydrodynamic radii of these complexes vary over a range of 20-35 nm. Overall results reveal that these complexes are qualitatively similar to the polyion complex micelles or block ionomer complexes obtained from the block copolymers and oppositely charged surfactants. As the surfactants used in this study are biocompatible, we hope that these soluble particles will be promising vectors in the field of drug delivery.

Complexes of poly(ethylene glycol)-based cationic random copolymer and calf thymus DNA: a complete biophysical characterization.

Complete biophysical characterization of complexes (polyplexes) of cationic polymers and DNA is needed to understand the mechanism underlying nonviral therapeutic gene transfer. In this article, we propose a new series of synthesized random cationic polymers (RCPs) from methoxy poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride with different mole ratios (32:68, 11:89, and 6:94) which could be used as a model system to address and answer the basic questions relating to the mechanism of the interaction of calf thymus DNA (CT-DNA) and cationic polymers. The solubility of the complexes of CT-DNA and RCP was followed by turbidity measurements. It has been observed that complexes of RCP with 68 mol % MePEGMA precipitate near the charge neutralization point, whereas complexes of the other two polymers are water-soluble and stable at all compositions. Dnase 1 digestion experiments show that DNA is inaccessible when it forms complexes with RCP. Ethidium bromide exclusion and gel electrophoretic mobility show that both polymers are capable of binding with CT-DNA. Atomic force microscopy images in conjunction with light scattering experiments showed that the complexes are spherical in nature and 75-100 nm in diameter. Circular dichroism spectroscopy studies indicated that the secondary structure of DNA in the complexes is not perturbed due to the presence of poly(ethylene glycol) segments in the polymer. Furthermore, we used a combination of spectroscopic and calorimetric techniques to determine complete thermodynamic profiles accompanying the helix-coil transition of CT-DNA in the complexes. UV and differential scanning calorimetry melting experiments revealed that DNA in the complexes is more stable than in the free state and the extent of stability depends on the polymer composition. Isothermal titration calorimetry experiments showed that the binding of these RCPs to CT-DNA is associated with small exothermic enthalpy changes. A complete thermodynamic profile showed that the RCP/DNA complex formation is entropically favorable. Much broader opportunities to vary the architecture of the polymers studied here make these systems promising in addressing various basic and practical problems in gene delivery systems.