Cationic Amphiphilic Copolymers Research Articles

Cationic amphiphilic acrylic copolymer retanning agent for metal-free eco-leather production

Producing metal-free leather is an effective approach to eliminate Cr pollution and achieve sustainable development of the leather industry. However, the high water sorption of the metal-free leather and the mismatching of the charge properties between the metal-free tanned leather and anionic post-tanning chemicals result in the unsatisfactory properties of the leather products, thereby restricting the industrial application of metal-free tanning technologies. Herein, a series of cationic amphiphilic acrylic copolymers (PSD) with different molar ratios of hydrophobic monomer to cationic hydrophilic monomer were synthesized and applied in the retanning of a metal-free tanned leather. PSD can effectively penetrate to the hierarchy of collagen fibril of leather and firmly bind to collagen carboxyls to form a thin hydrophobic coating on the fibril surface due to their small particle size (< 70 nm), excellent surface activity and cationic amine groups (3–27 μmol/g). Molecular dynamics (MD) simulations confirm that the primary driving force between PSD and collagen is electrostatic interaction. MD simulations and water resistance tests demonstrate that the amphiphilic PSD provides the metal-free leather with moderate hydrophobicity, which indicates the upgrade of the comprehensive properties of leather. PSD retanning enhances the uptake rate of anionic dyes and fatliquors (> 90 %) and endows the metal-free leather with excellent filling effect and bright color. The molar ratio of hydrophilic monomer and hydrophobic monomer plays an important role in the performance of PSD. The hydrophobic segments contribute to the hydrophobicity enhancement of leather, and the cationic hydrophilic segments in PSD contribute to the charge regulation of leather and robust binding of post-tanning chemicals. Hence, the multifunctional PSD retanning agents can fulfill the demands for versatile metal-free leather types and promise to boost the sustainable development of the leather industry.

Bioactive surfaces with well-defined amphiphilic copolymers containing a natural terpene-based monomer

New amphiphilic cationic copolymers based on poly((methacryloyloxy) ethyl trimethylammonium chloride) (PMETAC) and bio-based poly(thymol methacrylate) (PTMA) were prepared by atom transfer radical polymerization (ATRP) methods, using low concentration of metal catalyst and a bio-based eutectic mixture (EM), composed of L-menthol and thymol. The antimicrobial activity of the polymers was evaluated against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria.The results in solution showed that increasing the terpenic segment (PTMA) in the copolymers resulted in lower antimicrobial activity against S. aureus (as the MIC increases from 3.1 to 100 μM) and higher activity against E. coli (as the MIC decreases from 400 to 200 μM).Scanning electron microscopy (SEM) analysis suggests that polymers affected the bacterial viability by damaging the cell structure. The synthesized biocidal polymers were used as additives in polyurethane-based varnish formulations to produce bioactive coated surfaces that were found to be more active against E. coli. Coatings containing either PTMA or PMETAC homopolymers were more efficient than those containing PMETAC-co-PTMA copolymers. A dramatic improvement in the antimicrobial activity of PMETAC-containing varnish against both S. aureus (3 orders of magnitude) and E. coli (4 orders of magnitude) was observed when an aqueous solution of the homopolymer was applied to the dried varnish instead of being incorporated into the varnish formulation. The strategy presented here is simple and opens the door for the preparation of customized bioactive surfaces to prevent bacterial infections.

Synergy effect of bactericidal and antifouling with structure reversion and hydrolysis of cationic amphiphilic copolymer PHMA-b-PCBMAE to zwitterionic copolymer

In this study, cationic amphiphilic copolymers of poly(hexadecyl methacrylate)-b-poly(carboxybetaine methacrylate ester) (PHMA-b-PCBMAE) with hydrophobic unit of 100 were synthesized, which can be self-assembled as core-shell nanoparticles with PCBMAE as core and PHMA as shell in chloroform. In response to the change of solvent polarity from chloroform to methanol, the reversion ability of core-shell structure occurred to cationic amphiphilic polymers of PHMA100-b-PCBMAE40, PHMA100-b-PCBMAE50, PHMA100-b-PCBMAE75 and PHMA100-b-PCBMAE100 in an ascending order, which was verified by 1H NMR results. Coatings embedded with the cationic copolymers with PHMA:PCBMAE block ratios of 100:75 and 100:100 showed remarkably decreased water contact angle and protein adsorption amount due to the resulted zwitterionic copolymers upon hydrolysis in aqueous solution. Moreover, dynamic recording of the bactericidal activity against E. coli and S. aureus showed that it took ∼18 h for the copolymers PHMA100-b-PCBMAE75 and PHMA100-b-PCBMAE100 to take effect in bacteria killing and foulant repelling, and the bacteria left on the coating surfaces were <1.0 % in 24 h. The bactericidal results were in good accord with the trend of the nanoparticle reversion ability, indicating that higher PCBMAE contents of the cationic diblock copolymer facilitated core-shell reversion and subsequent hydrolysis to zwitterionic copolymer. Moreover, the regenerable surfaces of the coating furtherly ensured the sustainable bactericidal and antifouling activities.

PH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (β-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of ∼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the “ELVIS” effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the “proton sponge” effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 μg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.

Structure of micelleplexes formed between QPDMAEMA-b-PLMA amphiphilic cationic copolymer micelles and DNA of different lengths

We study the structures of micelleplexes formed by quaternized poly(2-(dimethylamino) ethyl methacrylate)-b-poly(lauryl methacrylate) (QPDMAEMA-b-PLMA) amphiphilic cationic copolymer micelles interacting electrostatically with linear DNA of different lengths (113 and 2000 base pairs). QPDMAEMA-b-PLMA copolymers form micelles in aqueous milieu, with PLMA hydrophobic cores and QPDMAEMA cationic coronas. Nanosized micelleplexes were formed after mixing QPDMAEMA-b-PLMA micelles with DNAs, in a wide range of N/P ratios (nitrogen (N) of amine group of QPDMAEMA over phosphate (P) groups of DNA), as shown by Ultraviolet–Visible (UV–Vis) and fluorescence spectroscopy. Light scattering techniques demonstrated the formation of well-defined micelleplexes with monomodal and narrow size distributions, whose size and surface charge vary according to the N/P ratio. Micelleplexes presented stability under certain salt concentration. Spherical and worm-like micelleplexes were visualized by cryogenic transmission electron microscopy (Cryo-TEM). Overall, QPMDAEMA-b-PLMA micelles can efficiently interact with DNA. The stability, morphology and complexation of the micelleplexes were found to depend on copolymer molecular mass, the hydrophilic/hydrophobic ratio, the micellar structure, the length of DNA, the N/P ratio and the ionic strength. The findings demonstrate that QPDMAEMA-b-PLMA polyelectrolyte copolymer micelles have prospects for their application as non-viral vectors for nucleic acids delivery and gene therapy.

Amphiphilic copolymers of dimethyl aminoethyl methacrylate and methyl methacrylate with controlled hydrophilicity for antialgal activity

AbstractBiofouling due to algae mass attachment has detrimental effects on the performance and economy of many manufacturing processes. In consideration of this, present research is focused to mitigate such effect through the development of environmentally benign active antialgal cationic amphiphilic copolymers of poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) and methyl methacrylate (MMA). The copolymers compositions were synthesized to tailor various characteristics to control surface biofilm formation and antialgal activities were determined through suspension assay. Biofilm formation of Dictyosphaerium sp. algae on the synthesized copolymers of different surface energies was ascertained by measuring chlorophyll A content and percent adhesion of algae. The copolymers antialgal performance enhanced with increase in PDMAEMA concentration as it exhibited the lowest contact angle as well as adhesion and minimum chlorophyll A contents. Algal adhesion on the surface of materials was also observed by optical microscopy. The copolymers with higher concentration of DMAEMA resulted in greater hydrophilicity which exhibited low adhesion of Dictyosphaerium algae due to possibility of stronger hydration effect and wettability as evident from their lower water contact angle. The developed benign cationic polymers of PDMAEMA and PMMA with varying compositions can lead to important breakthrough in the subject area of antialgal research in several manufacturing processes.

A new analytical approach for preconcentration, separation and determination of Pb(II) and Cd(II) in real samples using a new adsorbent: Synthesis, characterization and application

A green and efficient analytical approach was reported for simultaneous preconcentration, and separation of Pb(II) and Cd(II) in water, vegetables, and barbecue samples by dispersive solid-phase microextraction prior to their determination using flame atomic absorption spectrometry. A new poly-3-hydroxy butyrate-polyvinyl triethyl ammonium chloride comb-type amphiphilic cationic block copolymer (PHBvbNCl) was synthesized and characterized. Main variables such as pH, sorbent amount, adsorption time, eluent type, desorption time, and sample volume were optimized. Detection limits and working ranges for Pb(II) and Cd(II) were 0.03 μg L-1, 0.15 μg L-1, 0.1–250 μg L-1 and 0.5–375 μg L-1, respectively. Enhancement factor for Pb (II) and Cd (II) were 114 and 98. The adsorption capacity of PHBvbNCl for Pb(II) and Cd(II) was 175.2 mg g−1 and 152.9 mg g−1. After the accuracy of the method was confirmed by the analysis of certified reference materials, it was successfully applied to real samples. Finally, the analytical performance of the present method was compared with other methods.

The function of peptide-mimetic anionic groups and salt bridges in the antimicrobial activity and conformation of cationic amphiphilic copolymers.

Herein we report the synthesis of ternary statistical methacrylate copolymers comprising cationic ammonium (amino-ethyl methacrylate: AEMA), carboxylic acid (propanoic acid methacrylate: PAMA) and hydrophobic (ethyl methacrylate: EMA) side chain monomers, to study the functional role of anionic groups on their antimicrobial and hemolytic activities as well as the conformation of polymer chains. The hydrophobic monomer EMA was maintained at 40 mol% in all the polymers, with different percentages of cationic ammonium (AEMA) and anionic carboxylate (PAMA) side chains, resulting in different total net charge for the polymers. The antimicrobial and hemolytic activities of the copolymer were determined by the net charge of +3 or larger, suggesting that there was no distinct effect of the anionic carboxylate groups on the antimicrobial and hemolytic activities of the copolymers. However, the pH titration and atomic molecular dynamics simulations suggest that anionic groups may play a strong role in controlling the polymer conformation. This was achieved via formation of salt bridges between cationic and anionic groups, transiently crosslinking the polymer chain allowing dynamic switching between compact and extended conformations. These results suggest that inclusion of functional groups in general, other than the canonical hydrophobic and cationic groups in antimicrobial agents, may have broader implications in acquiring functional structures required for adequate antimicrobial activity. In order to explain the implications, we propose a molecular model in which formation of intra-chain, transient salt bridges, due to the presence of both anionic and cationic groups along the polymer, may function as “adhesives” which facilitate compact packing of the polymer chain to enable functional group interaction but without rigidly locking down the overall polymer structure, which may adversely affect their functional roles.

Screening and Matching Amphiphilic Cationic Polymers for Efficient Antibiosis.

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure-antibacterial activity relationship of these cationic polymers was investigated against E. coli and S. aureus, including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB35/T57) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB33/T56). Furthermore, mPB35/T57 with appropriate mole fraction of alkyl side chains (falkyl = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both E. coli (MIC = 8 μg/mL, selectivity > 250) and S. aureus (MIC = 4 μg/mL, selectivity > 500). More importantly, mPB35/T57 could effectively eradicate E. coli biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB35/T57 provided valuable information for improving the antibacterial activity of cationic polymers.

Erratum to: Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation

The authors regret that there was an error in our publication. Considering Lingchuang Bai made great contributions to this work, Xinghong Duo and Lingchuang Bai should be co-first authors, but there was no statement that “Xinghong Duo and Lingchuang Bai contributed equally to this work”. The authors would like to apologize for any inconvenience caused.

Hemolytic and Antimicrobial Activities of a Series of Cationic Amphiphilic Copolymers Comprised of Same Centered Comonomers with Thiazole Moieties and Polyethylene Glycol Derivatives.

A series of well-defined antimicrobial polymers composed of comonomers bearing thiazole ring (2-(((2-(4-methylthiazol-5-yl)ethoxy)carbonyl)oxy)ethyl methacrylate monomer (MTZ)) and non-hemotoxic poly(ethylene glycol) side chains (poly(ethylene glycol) methyl ether methacrylate (PEGMA)) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. By post-polymerization functionalization strategy, polymers were quaternized with either butyl or octyl iodides to result in cationic amphiphilic copolymers incorporating thiazolium groups, thus with variable hydrophobic/hydrophilic balance associated to the length of the alkylating agent. Likewise, the molar percentage of PEGMA was modulated in the copolymers, also affecting the amphiphilicity. The antimicrobial activities of these cationic polymers were determined against Gram-positive and Gram-negative bacteria and fungi. Minimum inhibitory concentration (MIC) was found to be dependent on both length of the alkyl hydrophobic chain and the content of PEGMA in the copolymers. More hydrophobic octylated copolymers were found to be more effective against all tested microorganisms. The incorporation of non-ionic hydrophilic units, PEGMA, reduces the hydrophobicity of the system and the activity is markedly reduced. This effect is dramatic in the case of butylated copolymers, in which the hydrophobic/hydrophilic balance is highly affected. The hemolytic properties of polymers analyzed against human red blood cells were greatly affected by the hydrophobic/hydrophilic balance of the copolymers and the content of PEGMA, which drastically reduces the hemotoxicity. The copolymers containing longer hydrophobic chain, octyl, are much more hemotoxic than their corresponding butylated copolymers.

Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating and nuclear accumulation

Gene therapy has drawn great attention in the treatments of many diseases, especially for cardiovascular diseases. However, the development of gene carriers with low cytotoxicity and multitargeting function is still a challenge. Herein, the multitargeting REDV-G-TAT-GNLS peptide was conjugated to amphiphilic cationic copolymer poly(e-caprolactone-co-3(S)-methyl-morpholine-2,5-dione)-g-polyethyleneimine (PCLMD-g-PEI) via a heterobifunctional orthopyridyl disulfide-poly(ethylene glycol)-N-hydroxysuccinimide (OPSS-PEG-NHS) linker to prepare PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop the gene carriers with low cytotoxicity and high transfection efficiency. The multitargeting micelles were prepared from PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers by selfassembly method and used to load pEGFP-ZNF580 plasmids (pDNA) to form gene complexes for enhancing the proliferation and migration of endothelial cells (ECs). The loading pDNA capacity was proved by agarose gel electrophoresis assay. These multitargeting gene complexes exhibited low cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The high internalization efficiency of these gene complexes was confirmed by flow cytometry. The results of in vitro transfection demonstrated that these multitargeting gene complexes possessed relatively high transfection efficiency. The rapid migration of ECs transfected by these gene complexes was verified by wound healing assay. Owing to ECs-targeting ability, cell-penetrating ability and nuclear targeting capacity of REDV-G-TAT-G-NLS peptide, the multitargeting polycationic gene carrier with low cytotoxicity and high transfection efficiency has great potential in gene therapy.

Preparation of poly(glutamic acid) shielding micelles self-assembled from polylysine-b-polyphenylalanine for gene and drug codelivery

A novel amphiphilic cationic block copolymer polylysine-b-polyphenylalanine (PLL-b-PPhe) was synthesized and self-assembled into micelles in aqueous solution, then shielded with poly(glutamic acid) (marked as PG/PLL-b-PPhe) to codeliver gene and drug for combination cancer therapy. Here, doxorubicin (DOX) was selected to be loaded into PLL-b-PPhe micelles and the drug loading efficiency was 8.0%. The drug release studies revealed that the PLL-b-PPhe micelles were pH sensitive and the released DOX could reach to 53.0%, 65.0%, 72.0% at pH 7.4, 6.8 and 5.0, respectively. In order to reduce positive charge and cytotoxicity of PLL-b-PPhe micelles, PG was used as shelding, simultaneously condensed with Bcl2 siRNA to form gene carrier system. Compared with PEI, PG/PLL-b-PPhe had excellent gene transfection efficiency, especially when the molar ratio of PLL to PPhe was 30:60 and the mixed mass ratio of PLL-b-PPhe to gene was 5:1. More importantly, DOX and Bcl2 siRNA gene codelivery system displayed remarkable cytotoxicity against B16F10 cells. Confocal laser scanning microscopy (CLSM) and flow cytometry were used to characterize endocytosis of the codelivery system, and confirmed that both DOX and Bcl2 siRNA had been endocytosed into B16F10 cells. The above results indicated that gene and drug codelivery was a promising strategy in future cancer therapy.

Facial Amphiphilicity-Induced Polymer Nanostructures for Antimicrobial Applications.

New antimicrobial agents are needed to address ever-increasing antimicrobial resistance and a growing epidemic of infections caused by multidrug resistant pathogens. We design nanostructured antimicrobial copolymers containing multicyclic natural products that bear facial amphiphilicity. Bile acid based macromolecular architectures of these nanostructures can interact preferentially with bacterial membranes. Incorporation of polyethylene glycol into the copolymers not only improved the colloidal stability of nanostructures but also increased the biocompatibility. This study investigated the effects of facial amphiphilicity, polymer architectures, and self-assembled nanostructures on antimicrobial activity. Advanced nanostructures such as spheres, vesicles, and rod-shaped aggregates are formed in water from the facial amphiphilic cationic copolymers via supramolecular interactions. These aggregates were particularly interactive toward Gram-positive and Gram-negative bacterial cell membranes and showed low hemolysis against mammalian cells.

Sequential-targeting nanocarriers with pH-controlled charge reversal for enhanced mitochondria-located photodynamic-immunotherapy of cancer

Targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) by positively charged polymeric nanocarriers (NCs) is one of the useful methods for efficient photodynamic therapy (PDT). However, the NCs with positively charged mitochondria-targeting moieties are easily cleaned during circulation, restricting their in vivo applications. Herein, to address this issue and enhance in vivo PDT efficacy, we developed a sequential-targeting delivery system consisting of mitochondria-targeting micelles as the core prepared from the cationic amphiphilic copolymer for loading chlorin e6 (Ce6) and a tumor-targeting pH-dependent charge transformational layer as the shell obtained from 2,3-dimethylmaleic anhydride modified Biotin-PEG4000-NH2 (BioPEGDMA) via electrostatic interaction. Concealed by the anionic shell, the as-prepared NCs showed longer retention within the first stage of tumor-targeting. Then, the accumulated NCs conversed to positive charge in tumor extracellular microenvironment (pH ∼ 6.5), which could be more effectively internalized by tumor cells, and the re-exposed triphenylphosphonium (TPP) groups endowed their second-stage targetability to the mitochondria. In vivo experiments revealed that the Ce6-loaded NCs exhibited remarkable tumor inhibition rates of 84.1% and 93.2% on BALB/c nude mice and Kunming mice, respectively, under 660 nm NIR irradiation, and stimulated immune responses with upregulated expression of IFN-γ, TNF-α and CD3+ in tumor tissues, and enhanced activation of CD3+/CD4+, CD3+/CD8+ T lymphocytes and DCs in both tumor tissues and lymph glands. This work provided a new pathway for the development of smart drug delivery system with advanced PDT efficacy. Statement of significanceAlthough the existing targeting delivery of photosensitizers to mitochondria by positively charged nanocarriers (NCs) have efficiently enhanced photodynamic therapy (PDT), their positive charges caused rapid clearance during circulation, which has restricted their in vivo applications. Therefore, we fabricated a novel sequential-targeting NC to solve the problem. The tumor accumulated NCs conversed to positive charge in tumor extracellular microenvironment, and the re-exposed triphenylphosphonium groups initiated second-stage targetability to mitochondria. This system exhibited remarkable tumor inhibition efficiency both in vitro and in vivo. Moreover, as we hypothesized, mitochondria-located PDT could promote immune response, resulting in improvement of PDT. The strategy of sequential targeting-based PDT in combination with augmented immune response showed a novel pathway for the development of smart drug delivery system with advanced PDT.

A cationic amphiphilic co-polymer as a carrier of nucleic acid nanoparticles (Nanps) for controlled gene silencing, immunostimulation, and biodistribution

Programmable nucleic acid nanoparticles (NANPs) provide controlled coordination of therapeutic nucleic acids (TNAs) and other biological functionalities. Beyond multivalence, recent reports demonstrate that NANP technology can also elicit a specific immune response, adding another layer of customizability to this innovative approach. While the delivery of nucleic acids remains a challenge, new carriers are introduced and tested continuously. Polymeric platforms have proven to be efficient in shielding nucleic acid cargos from nuclease degradation while promoting their delivery and intracellular release. Here, we venture beyond the delivery of conventional TNAs and combine the stable cationic poly-(lactide-co-glycolide)-graft-polyethylenimine with functionalized NANPs. Furthermore, we compare several representative NANPs to assess how their overall structures influence their delivery with the same carrier. An extensive study of various formulations both in vitro and in vivo reveals differences in their immunostimulatory activity, gene silencing efficiency, and biodistribution, with fibrous NANPs advancing for TNA delivery.

Redox-Responsive Efficient DNA and Drug Co-Release from Micelleplexes Formed from a Fluorescent Cationic Amphiphilic Polymer.

Cationic polymeric micelles that are capable of co-releasing drugs and DNA into cells have attracted considerable interest as combination chemotherapy in cancer treatment. To this effect, we have presently developed a cationic fluorescent amphiphilic copolymer, poly(N,N'-dimethylaminoethylmethacrylate)-b-(poly(2-(methacryloyl)oxyethyl-2'-hydroxyethyl disulfidecholate)-r-2-(methacryloyloxy)ethyl-1-pyrenebutyrate) [PDMAEMA-b-(PMAODCA-r-PPBA)], having pendent cholate moiety linked through a redox-responsive disulfide bond. The amphiphilic nature of the copolymer facilitated the formation of cationic micellar nanoparticles in aqueous medium. The self-assembly of the copolymer to form micelles and subsequent destabilization of the micelles in the presence of glutathione (GSH) was monitored by the change in the fluorescence characteristic of the attached pyrene resulting from alteration in the hydrophobicity of its neighborhood. These micellar nanoparticles were subsequently utilized in encapsulating hydrophobic anticancer drug, doxorubicin (DOX), in the core of the micelles, whereas the cationic shell of the micelles was used for complexation with oppositely charged DNA to form micelleplexes. Gel retardation assays, ethidium bromide (EB) exclusion assay, and DLS and AFM studies confirmed the successful binding of the cationic micelles with DNA. The binding capability of the micelles was higher than corresponding cationic linear PDMAEMA. The kinetics of the simultaneous release of encapsulated DOX and complexed DNA in the presence of glutathione was thoroughly studied using various techniques. All the experiments showed fast and efficient release of DOX and DNA from DOX-loaded micelleplexes. The study implies that these redox-responsive cationic micelles may open up new opportunities toward co-delivery of DNA and anticancer drugs in combinatorial therapy.

A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer.

BackgroundAn amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model.Materials and methodsThe transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays.ResultsThe transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection.ConclusionChol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response.

Redox-responsive micelles self-assembled from multi-block copolymer for co-delivery of siRNA and hydrophobic anticancer drug

Novel redox-responsive amphiphilic cationic multi-block copolymers PEG2000–PLA3000–PEI1200–PLA3000–PEG2000 and PEG2000–PLA3000–PEI1800–PLA3000–PEG2000 were synthesized and self-assembled into micelles for co-delivery of siRNA and hydrophobic doxorubicin (DOX). The chemical structure and molecular weight of the copolymers were characterized by 1H nuclear magnetic resonance and gel permeation chromatography, respectively. The copolymeric micelles were examined by dynamic light scattering, and their size, zeta potential and critical micelle concentration were determined. The in vitro drug release analyses indicated that reductive environment can trigger the release of DOX and siRNA by breaking the micelles. MTT assay demonstrated that the DOX/siRNA-loaded micelles are capable of inhibiting proliferation of SGC7901 cells. The results of fluorescence microscopy and flow cytometry verify the simultaneous delivery of DOX and siRNA from the nanomicellar particles into SGC7901 cells. The reduction-responsive cationic copolymers will provide a platform for constructing drug/gene delivery system toward cancer therapy.

Self-assembly of cationic amphiphilic cellulose-g-poly (p-dioxanone) copolymers

Cationic amphiphilic cellulose copolymers were prepared through grafting hydrophobic poly (p-dioxanone) (PPDO) chains onto hydrophilic quaternized cellulose derivatives (QC) via ring-opening polymerization (ROP) reaction, which was performed in 1-butyl-3-methylimidazolium chloride (BmimCl) and using 4-dimethylaminopyridine (DMAP) or 1,8-diazabicyclo (5.4.0) undec-7-ene (DBU) as catalyst. Their chemical structures and physical properties were confirmed by FT-IR, 1H-, 13C-, 2D HSQC-NMR, X-ray diffraction (XRD), and thermal stability (TGA) techniques, while self-assembly behavior was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and fluorescence techniques. Both of the sizes and critical micelle concentration (CMC) values of micelles were decreased with increasing grafting contents of PPDO in the copolymers, which were in the ranges of 110–246 nm and 64–253 μg/mL, respectively. The ζ-potentials of micelles were cationic andranged from 39.1 mV to 45.4 mV. The highest encapsulation efficiencyof paclitaxel (PTX) into the micelles was 61.8% and 92.0% of loaded PTX was continuously released from micelles in phosphate buffered saline medium for 36 h.