Low Molecular Weight Polyethylenimine Research Articles

Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting

BackgroundA degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector.MethodsWe crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-TAT (49–57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo.ResultsThe vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150–250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/μg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 μg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13.ConclusionOTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy.

Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by a mTOR siRNA-loaded cyclodextrin nanovector

The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH), an intractable disease, for which pharmacotherapy is limited and only slight improvement in survival outcomes have achieved over the past few decades. RNA interference provides a highly promising strategy to the treatment of this chronic lung disease, while efficient delivery of small interfering RNA (siRNA) remains a key challenge for the development of clinically acceptable siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid nanoplatform gave rise to desirable siRNA loading, and the payload release could be modulated by the hydrolysis characteristics of carrier materials. Fluorescence observation and flow cytometry quantification suggested that both Ac-aCD and PLGA nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as well as in the presence of serum, with uptake and transfection efficiency significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic PASMCs, largely resulting from effective suppression of mTOR signaling as evidenced by significantly lowered expression of mTOR mRNA and phosphorylated protein. Moreover, these hybrid nanomedicines were more effective than commonly used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV may be promising therapeutics for diseases related to hypoxic abnormal growth of PASMCs.

Synthesis and characterization of guanidinylated polyethylenimine-conjugated chitosan for gene delivery systems

In this work, guanidinylated polyethylenimine-conjugated chitosan (CS-PEI-G) was synthesized, and characterized for efficient gene delivery systems. Low molecular weight PEI (0.8 kDa) was conjugated to chitosan as a low cytotoxic template for introducing the integrated bio-functionalities and guanidine groups, which are important components of cellular penetrating peptides. Synthesized CS-PEI-G could form positively charged and nano-sized complexes with pDNA. CS-PEI-G showed enhanced transfection efficiency in comparison with unmodified CSPEI, and high transfection efficiency comparable to or higher than PEI25k, due to guanidine moieties and the serum stability of chitosan backbone. Flow cytometry results suggest that the improved transfection efficiency of CS-PEIG may be not induced by cellular uptake of polyplexes but by other factors, such as the nuclear localization ability of guanidine moieties. These results showed that the simple strategy of introducing the guanidine groups of high density to chitosan via small PEI linkers could be effective for developing efficient gene delivery carriers.

폴리디아세틸렌 리포좀 표면에 저분자량의 폴리에틸렌이민을 연결한 새로운 유전자 전달체 합성 및 특징 연구

본 논문은 저분자량의 폴리에틸렌이민을 폴리디아세틸렌 리포좀 표면에 연결하여 유전자를 세포 내로 전달할 수 있는 새로운 양이온성 고분자 리포좀 유전자 전달체 개발에 대한 결과이다. 폴리디아세틸렌 리포좀 제조 후에 자외선을 조사하여 고분자성 리포좀을 제조한 후, 유전자의 전달 효율을 높이기 위해 폴리에틸렌이민을 리포좀 표면에 커플링제를 이용하여 공유결합시켜서 PCDA-PEI 리포좀을 합성하였다. 제조한 고분자 리포좀을 이용하여 동물세포 내에서의 유전자 전달 및 발현 효율과 그에 따른 독성을 확인하는 연구를 수행하였다. 사용한 폴리에틸렌이민은 가지형이고 분자량은 2 kD인 것을 사용하였다. DNA와의 복합체 형성을 알아보기 위하여 전기영동 방법과 피코그린 형광 염색 시약을 사용하였으며 효율적으로 복합체를 형성하는 것을 확인하였다. 전달체의 효율과 독성을 확인하기 위하여 HEK 293 및 HeLa 세포를 사용하여 확인하였다. 실험 결과 PCDA-PEI 리포좀은 세포 내에서 비율이 높아질수록 유전자 전달 효율이 증가하는 경향을 보였고, 세포에 대한 독성도 상대적으로 낮음을 확인하였다. 이러한 결과는 PCDA-PEI 리포좀이 효율적인 유전자 혹은 약물 전달체로 사용될 수 있음을 보여주었다. In this paper, we made a new polycationic polymeric liposome composed of low molecular weight polyethylenimine (PEI) and 10,12-pentacosadiynoic acid (PCDA). PCDA liposome was prepared by ultraviolet irradiation. PEI was further conjugated on the surface of the polymerized PCDA liposome using coupling reagents to make PCDA-PEI. The blue-to-red transition of PCDA liposome was observed during the coupling reaction. The size distribution of liposome and complexes with plasmid DNA was measured by dynamic light scattering (DLS). The complex formation was also identified by agarose gel electrophoresis and PicoGreen reagent assay. We confirmed the complex formation of the polymeric liposome with DNA and then performed transfection and cytotoxicity assay in HEK 293 and HeLa cells. As a result, PCDA-PEI showed significant gene transfection efficiency and low cytotoxicity. This study shows that PEI-conjugated PCDA liposome could be an efficient gene or drug delivery carrier.

Chitosan-Graft-Polyethylenimine/DNA Nanoparticles as Novel Non-Viral Gene Delivery Vectors Targeting Osteoarthritis

The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. The present study was designed to develop and evaluate the chitosan-graft-polyethylenimine (CP)/DNA nanoparticles as novel non-viral gene vectors for gene therapy of osteoarthritis. The CP/DNA nanoparticles were produced through a complex coacervation of the cationic polymers with pEGFP after grafting chitosan (CS) with a low molecular weight (Mw) PEI (Mw = 1.8 kDa). Particle size and zeta potential were related to the weight ratio of CP:DNA, where decreases in nanoparticle size and increases in surface charge were observed as CP content increased. The buffering capacity of CP was significantly greater than that of CS. The transfection efficiency of CP/DNA nanoparticles was similar with that of the Lipofectamine™ 2000, and significantly higher than that of CS/DNA and PEI (25 kDa)/DNA nanoparticles. The transfection efficiency of the CP/DNA nanoparticles was dependent on the weight ratio of CP:DNA (w/w). The average cell viability after the treatment with CP/DNA nanoparticles was over 90% in both chondrocytes and synoviocytes, which was much higher than that of PEI (25 kDa)/DNA nanoparticles. The CP copolymers efficiently carried the pDNA inside chondrocytes and synoviocytes, and the pDNA was detected entering into nucleus. These results suggest that CP/DNA nanoparticles with improved transfection efficiency and low cytotoxicity might be a safe and efficient non-viral vector for gene delivery to both chondrocytes and synoviocytes.

Proliferation and migration of human vascular endothelial cells mediated by ZNF580 gene complexed with mPEG-b-P(MMD-co-GA)-g-PEI microparticles.

Herein, we developed a novel biodegradable gene carrier for rapid endothelialization of endothelial cells (ECs) in vitro. Three triblock amphiphilic copolymers, methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-2,5-morpholinedione-co-glycolide)-graft-polyethyleneimine (mPEG-b-P(MMD-co-GA)-g-PEI) with different 3(S)-methyl-2,5-morpholinedione and glycolide contents were synthesized. Microparticles (MPs) were obtained via self-assembly of these copolymers. The hydrophobic core composed of P(MMD-co-GA) segments provide crosslinking points for numbers of PEG and short PEI chains to form a highly hydrophilic and positively charged corona/shell of MPs. Using these MPs, potential genes (ZNF580) for rapid endothelialization were efficiently transported into EA.hy926 cells. Because of the hydrophilic PEG chains and low molecular weight PEI in the triblock copolymers, the cytotoxicity of these MPs and their complexes with pEGFP-ZNF580 was decreased significantly. The transfection efficacy of MPs/pEGFP-ZNF580 complexes was as high as Lipofectamine™ 2000 reagent to EA.hy926 cells in vitro. The proliferation and migration of EA.hy926 cells were improved greatly by the expression of pEGFP-ZNF580 after 60 hours. Our results indicated that the mPEG-b-P(MMD-co-GA)-g-PEI based MPs could be a suitable non-viral gene carrier for ZNF580 gene to enhance rapid endothelialization.

Preparation and evaluation of polyethyleneimine-single walled carbon nanotube conjugates as vectors for pancreatic cancer treatment.

High quality single-walled carbon nanotubes (SWNTs) were obtained following a new purification procedure, based on using Cl2 gas at high temperature. Cl2-treated SWNTs were fluorinated and modified with branched polyethyleneimine (PEI) to afford covalently functionalised PEI-SWNTs, which were then tested for cytotoxicity both in vitro (HPNE and BxPC3 pancreatic cell lines) and in vivo (BxPC3 xenografts from nude mice) to establish that functionalization with lower molecular weight PEI (600 and 1800 Da) achieved higher cell viability in MTT assay. A shortened version of the nanotubes, PEI(1800)-cut-SWNT (1800 Da branched PEI), was also prepared and tested for cellular internalization in the BxPC3 adenocarcinoma cell line. Laser confocal imaging of the cells after incubation in the presence of RhoB-PEI(1800)-cut-SWNT (covalently labelled with rhodamine B) indicates that the PEI(1800)-cut-SWNTs can reach both the cytoplasm and nucleus of pancreatic cancer cells.

Pharmacokinetics and transgene expression of implanted polyethylenimine-based pDNA complexes.

Locally delivered plasmid DNA (pDNA) is currently pursued as gene-based therapy for regenerative medicine, but important information on in situ pDNA pharmacokinetics and transgene expression is lacking in animal models. To investigate pDNA pharmacokinetics in implants, low molecular weight (2 kDa) polyethylenimine (PEI) and linoleic acid substituted 2 kDa PEI (PEI-LA) were used for pDNA delivery in gelatin sponges. An efficient pDNA extraction method combined with quantitative PCR (qPCR) was found to give equivalent quantitation of naked and polymer-bound pDNA, making it suitable to assess pDNA polyplexes in implants. Naked pDNA implanted in a rat subcutaneous model was >98% lost after 24 hours whereas PEI and PEI-LA delivered pDNA remained intact in implants for 2 and 4 weeks, respectively. Using a plasmid expressing DsRed as a reporter gene, mRNA and protein expression was observed only for PEI-LA despite the extended retention and cellular uptake of PEI complexes. The in vivo data were in agreement with in vitro results showing that only PEI-LA was an effective transfection agent even though both PEI and PEI-LA complexes were internalized by the cells. Dose dependence was observed for mRNA expression, with a 20 μg dose giving faster onset and higher expression levels compared to a 5 μg pDNA dose. The mRNA expression after PEI-LA mediated delivery was sustained for at least 4 weeks and a significant correlation between pDNA retention in sponges and mRNA expression was observed. In addition to establishing a promising gene carrier for gene delivery, these studies provided important information about the retention and transgene expression by implanted non-viral carriers.

Inositol based non-viral vectors for transgene expression in human cervical carcinoma and hepatoma cell lines

Myo-Inositol (INO) is a biomolecule with crucial functions in many aspects. In this study, hyperbranched copolymers for gene delivery were synthesized based on inositol and low molecular weight polyethylenimine. The capacity of INO-PEIs to load plasmid DNA and their biocompatibility was demonstrated. A tumor target ligand, folic acid (FA), which was widely used for drug delivery systems, was subsequently conjugated to INO-PEIs and resulted in INO-PEI-FA copolymers. The polymers were then evaluated on their activity to mediate transgene expression in mammalian cell lines. As indicated, INO-PEIs were able to mediate efficient transgene expression, which was particularly noticeable in carcinoma cell line HeLa. INO-PEI-FA further improved the efficiency in HepG2. Distribution of INO-PEI-FA polymers in non-carcinoma NIH 3T3 and carcinoma HeLa cell lines was discussed.

Hydrophobic modified low molecular weight polyethylenimine as protein carrier for therapeutic vaccine

Hydrophobic modified low molecular weight polyethylenimine as protein carrier for therapeutic vaccine

Reduction-sensitive non-viral gene vectors based on thioctic acid-substituted low molecular weight polyethylenimine

Reduction-sensitive non-viral gene vectors based on thioctic acid-substituted low molecular weight polyethylenimine

Polyxylitol-based gene carrier improves the efficiency of gene transfer through enhanced endosomal osmolysis

Endosomal escape is one of the important processes for efficient non-viral gene delivery. In this study, we synthesized a novel non-viral vector called polyxylitol-based gene carrier (XGC) through a Miachael addition reaction between xylitol diacrylate as a crosslinking agent and low molecular weight polyethylenimine (PEI 1.2kDa). The small amount of xylitol integrated into XGC (3.9% w/w) contributed 50% of the osmotic pressure of XGC, and enhaned the osmolysis of endosome cooperatively with the proton sponge effect, thus improving endosomal escape. Furthermore, XGC showed higher transfection efficiency in vivo in muscle tissue than pDNA alone or PEI 25kDa. In conclusion, our results show that XGC enhanced transfection efficiency compared with PEI 25kDa, the golden standard non-viral gene carrier, by enhancing endosomal escape without increasing the number of transfected cells. From the Clinical EditorEnhanced gene delivery methods would greatly facilitate the development of gene therapies. These authors demonstrate that a polyxylitol-based gene carrier enhanced the transfection efficiency compared with the gold standard non-viral gene carrier, as a result of enhancing endosomal escape without increasing the number of transfected cells, warranting further studies of this method.

Effective down‐regulation of signal transducer and activator of transcription 3 (STAT3) by polyplexes of siRNA and lipid‐substituted polyethyleneimine for sensitization of breast tumor cells to conventional chemotherapy

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays a major role in the development of resistance to conventional anti-cancer drugs in many types of cancer, when constitutively activated. Inhibition of STAT3 is considered as a promising strategy for inhibition of tumor growth and overcoming the drug resistance manifested. In this study, the capability of STAT3 knockdown by lipid substituted low molecular weight (2 kDa) polyethyleneimine (PEI2) complexes of STAT3-siRNA was assessed. The efficiency of PEI/STAT3-siRNA polyplexes in the induction of STAT3 associated cell death in wild type and drug-resistant MDA-MB-435 breast cancer cells as monotherapy and upon combination with chemotherapeutic agents, doxorubicin and paclitaxel, was also investigated. Our results identified linoleic acid-substituted (PEI-LA) polymer as the most efficient carrier among different lipid substituted PEI2 for siRNA delivery, leading to most STAT3 associated loss of cell viability in MDA-MB-435 cells. STAT3-siRNA delivery by the PEI-LA polymer resulted in efficient down-regulation of STAT3 at both mRNA and protein levels. Furthermore, pre-treatment of cancer cells with STAT3-siRNA formulation increased the cytotoxic effect of doxorubicin and paclitaxel in both wild type and drug resistant MDA-MB-435 cells. The results of this study point to the potential of PEI-LA polyplexes of STAT3-siRNA as inhibitors of STAT3 expression in breast tumor cells. The results also demonstrate an improved efficacy for chemotherapeutic drugs in combination with lipid-substituted low molecular weight PEI-LA/STAT3-siRNA complexes in comparison to drug therapy alone.

Effective down-regulation of signal transducer and activator of transcription 3 (STAT3) by polyplexes of siRNA and lipid-substituted polyethyleneimine for sensitization of breast tumor cells to conventional chemotherapy

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays a major role in the development of resistance to conventional anti-cancer drugs in many types of cancer, when constitutively activated. Inhibition of STAT3 is considered as a promising strategy for inhibition of tumor growth and overcoming the drug resistance manifested. In this study, the capability of STAT3 knockdown by lipid substituted low molecular weight (2 kDa) polyethyleneimine (PEI2) complexes of STAT3–siRNA was assessed. The efficiency of PEI/STAT3-siRNA polyplexes in the induction of STAT3 associated cell death in wild type and drug-resistant MDA-MB-435 breast cancer cells as monotherapy and upon combination with chemotherapeutic agents, doxorubicin and paclitaxel, was also investigated. Our results identified linoleic acid-substituted (PEI-LA) polymer as the most efficient carrier among different lipid substituted PEI2 for siRNA delivery, leading to most STAT3 associated loss of cell viability in MDA-MB-435 cells. STAT3-siRNA delivery by the PEI-LA polymer resulted in efficient down-regulation of STAT3 at both mRNA and protein levels. Furthermore, pre-treatment of cancer cells with STAT3–siRNA formulation increased the cytotoxic effect of doxorubicin and paclitaxel in both wild type and drug resistant MDA-MB-435 cells. The results of this study point to the potential of PEI-LA polyplexes of STAT3–siRNA as inhibitors of STAT3 expression in breast tumor cells. The results also demonstrate an improved efficacy for chemotherapeutic drugs in combination with lipid-substituted low molecular weight PEI-LA/STAT3-siRNA complexes in comparison to drug therapy alone. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3216–3228, 2014.

Polyethyleneimine‐poly(ethylene glycol)‐star‐copolymers as efficient and biodegradable vectors for mammalian cell transfection

High molecular weight (MW) polyethyleneimine (PEI) has been successfully used for the transfection of a broad variety of cell lines. In contrast to low MW PEI, which exhibits low transfection efficiencies but also low cytotoxicity, high MW PEI-mediated transfection achieves much higher efficiencies but at the cost of cell viability; therefore its use in commercial scale transfection and clinical application is limited. In this work we address this problem by constructing biodegradable high MW PEI mimics built from low MW PEI building blocks. The end-groups of small 5-arm star polyethylene glycol (PEG) prepolymers were decorated with linear oligo-ethyleneimine (OEI)/PEI arms of various MW via azomethine linkages. The resultant PEI-PEG-star-copolymers were investigated for their ability to complex plasmid DNA. Polymer/DNA complexes were characterized using techniques such as dynamic light scattering and transmission electron microscopy. Having established their cytotoxicity limits, they were tested as gene delivery vehicles for the transfection of suspension adapted Chinese hamster ovary (CHO-S) cells under serum-free conditions and adherent human embryonic kidney cells (HEK293T) in serum containing medium. Our PEI-PEG-star-copolymers showed a reduced cytotoxicity compared to high MW PEI while maintaining the ability to complex plasmid DNA and transfect mammalian cells, with significant transfection efficiencies. The effects of the optimum parameters on the transfection of mammalian cells using such novel polymers are discussed.

Phospholipid-modified polyethylenimine-based nanopreparations for siRNA–mediated gene silencing: Implications for transfection and the role of lipid components

The clinical application of gene silencing mediated by small interfering RNA (siRNA) has been limited by the lack of efficient and safe carriers. Phospholipid modification of low molecular weight polyethylenimine (PEI 1.8kDa) dramatically increased its gene down-regulation capacity while keeping cytotoxicity levels low. The silencing efficacy was highly dependent on the nature of the lipid grafted to PEI and the polymer/siRNA ratio employed. Phosphoethanolamine (DOPE and DPPE) and phosphocholine (PC) conjugation did not change the physicochemical properties and siRNA binding capacity of PEI complexes but had a large impact on their transfection and ability to down-regulate Green Fluorescent Protein (GFP) expression (60%, 30% and 5% decrease of GFP expression respectively). We found that the micelle-forming structure of DOPE and DPPE-PEI dramatically changed PEI's interaction with cell membranes and played a key role in promoting PEI 1.8kDa transfection, completely ineffective in the absence of the lipid modification. From the Clinical EditorWhile siRNA-based gene silencing methods could have numerous clinical applications, efficient delivery remains a major challenge. This team reports that DOPE-PEI and DPPE-PEI based micelle-forming nanostructures may be able to provide an efficient vector for siRNA transfection.

Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection

Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is known to increase gene transfection efficiency of LMW PEI. However, few studies have explored how the conjugated hydrophobic groups influence the properties of the modified LMW PEI mainly due to difficulties in obtaining well defined final product compositions and limitations in current chemical synthesis routes. The aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with different hydrophobic functional groups and to investigate how hydrophobicity, molecular structure and inclusion of hydrogen bonding properties in the conjugated side groups as well as the conjugation degree (number of primary amine groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene transfection efficiency. The modified polymers were characterized for DNA binding ability, particle size, zeta potential, in vitro gene transfection efficiency and cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell lines. The study shows that modified PEI-1.8 polymers are able to condense plasmid DNA into cationic nanoparticles, of sizes ∼100 nm, whereas unmodified polymer/DNA complexes display larger particle sizes of 2 μm. Hydrophobic modification also increases the zeta potential of polymer/DNA complexes. Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8 is modified with shorter hydrophobic groups (MTC–ethyl) as opposed to longer ones (MTC–octyl and MTC–deodecyl). An aromatic structured functional group (MTC–benzyl) also enhances transfection efficiency more than an alkyl functional group (MTC–octyl). An added hydrogen-bonding urea group in the conjugated functional group (MTC–urea) does not enhance transfection efficiency over one without urea (MTC–benzyl). The study also demonstrates that modification degree greatly influences gene transfection, and ∼100% substitution of primary amine groups leads to significantly lower gene transfection efficiency. These findings provide insights to modification of PEI for development of effective and non-cytotoxic non-viral vectors.

Biodegradable cationic nanoparticles loaded with an anticancer drug for deep penetration of heterogeneous tumours

To enhance limited drug penetration that mediated drug resistance and heterogeneity within the tumour microenvironment, we designed a paclitaxel (PTX) loaded degradable cationic nanogel (DpNG) consisted with acetylated pullulan and low molecular weight polyethyleneimine (LowbPEI, 1.8 kDa). The restoration of cationic charge on the DpNG was achieved via HA degradation by hyaluronidase which is secreted in tumour. The size and surface charge of HA-coated DpNG loaded with PTX (HA/DpNG-PTX) was 200–250 nm and 0 mV, respectively. The DpNG-PTX was showed significant cytotoxicity in heterogeneous cancer cells. The IC50 value of DpNG-PTX was 100 times less than that of free PTX. The growth of heterogeneous tumour in Balb/c mice was inhibited via intravenous injection of HA/DpNG-PTX. Furthermore, the invasive distance and amount of HA/DpNG-PTX localised within the deep tissue regions were increased two times than that of PA-PTX. Therefore, the DpNG based drug delivery system could be useful for treatment of heterogeneous tumour.

Effects of physico-chemical properties between poly(ethyleneimine) and silica abrasive on copper chemical mechanical planarization

We investigated the effect of poly (ethyleneimine) (PEI)-modified silica abrasive on the removal rate and the degree of dishing during Cu chemical mechanical planarization (CMP). The PEI-modified silica abrasive was prepared by mutually attractive electrostatic forces between PEI and silica abrasive. The physico-chemical behaviors between PEI and the silica abrasive were evaluated by total organic carbon (TOC), force-separation measurements using atomic force microscopy (AFM) with molecular weight of PEI, which was found to adsorb on silica at pH 7.0 following a Langmuir isotherm. The maximum adsorbed amounts of low and high molecular weight PEI were 0.195mg/m2 and 0.228mg/m2, respectively. AFM results showed the repulsive force of the adsorbed PEI layers on the silica surface and the adsorption thickness of PEI on silica vary with the molecular weight of PEI. A twofold change was observed in the AFM analysis. First, the increased areal density of adsorbed PEI caused a higher zeta-potential and longer reaching repulsive force. Second, the adsorption thickness was also significantly enlarged. High molecular weight showed increased adsorption thickness under similar conditions compared to low molecular weight of PEI. These changes of silica abrasive such as electrostatic forces and steric interaction vary with molecular weight of PEI reduced the dishing of Cu pattern film from 50 to 20nm.

Terminal modification on mPEG-dendritic poly-(l)-lysine cationic diblock copolymer for efficient gene delivery

The development of new non-viral gene vectors with the advantages of low cytotoxicity and high gene transfection efficiency is a recent trend in gene therapy. In this work, we developed a series of termini-modified mPEG-dendritic poly-(l)-lysine cationic diblock copolymers (mPEG5k-DPL4-CG) by coupling various cationic groups to the dendritic skeleton. Their molecular structures were characterized by 1H NMR, and the buffering capacities were measured by acid titration. The plasmid DNA (pDNA) binding affinities of the mPEG5k-DPL4-CG copolymers were investigated by EB displacement and agarose gel retardation assay, and the average particle size and surface charge of the polyplexes were analyzed by dynamic light scattering. Cytotoxicity and in vitro gene transfection were evaluated in several cell lines in the presence and absence of serum by the luciferase expression assay. The results indicated that the low molecular weight polyethylenimine (PEI800) termini-modified copolymer, mPEG5k-DPL4-PEI800, possessed high pDNA binding affinity, low cytotoxicity, and high gene transfection capability which were maintained in the presence of serum (10% FBS). It is worth noting that the gene delivery efficiency of the dendritic poly-(l)-lysine gene vector was enhanced by termini modification of suitable cationic blocks. The low cytotoxicity and serum-resistance properties of mPEG5k-DPL4-PEI800 make it a potential long-circulating gene vector in gene therapy applications.