Abstract:
:RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via an RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as liRNA, capable of executing RNAi mediated specific target gene silencing. In this study, we developed a highly effective liRNA based targeted delivery system to apply in the treatment of glioblastoma multiforme. A stable nanocomplex was fabricated by complexing multimerized liRNA structures with cross-linked branched poly(ethylene imine) (bPEI) via electrostatic interactions. We show clear evidence that the cross-linked bPEI was quite effective in enhancing the cellular uptake of liRNA on U87MG cells. Moreover, the liRNA-PEI nanocomplex provided strong RNAi mediated target gene silencing compared to that of the conventional siRNA-PEI complex. Further, the bPEI modification strategy with specific ligand attachment assisted the uptake of the liRNA-PEI complex on the mouse brain endothelial cell line (b.End3). Such delivery systems combining the beneficial elements of targeted delivery, controlled immunostimulation, and RNAi mediated target silencing have immense potential in anticancer therapy.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Sajeesh S,Lee TY,Hong SW,Dua P,Choe JY,Kang A,Yun WS,Song C,Park SH,Kim S,Li C,Lee DKdoi
10.1021/mp400541zsubject
Has Abstractpub_date
2014-03-03 00:00:00pages
872-84issue
3eissn
1543-8384issn
1543-8392journal_volume
11pub_type
杂志文章abstract::The present study explores the potential of polyelectrolyte-coated liposomes for improving the oral deliverability of doxorubicin (Dox). As a part of formulation strategy, stearyl amine was selected as a formulation component to provide positive charge to liposomes, which were subsequently coated with anionic poly(acr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300202c
更新日期:2012-09-04 00:00:00
abstract::The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500464b
更新日期:2015-04-06 00:00:00
abstract::Adsorption of antibody therapeutics to air-liquid interfaces can enhance aggregation, particularly when the solution does not contain protective surfactant or when the surfactant is diluted as occurs during preparation of intravenous infusion bags. The ability to predict an antibody's propensity for interfacially medi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00089
更新日期:2015-09-08 00:00:00
abstract::Itraconazole is a drug of choice for the treatment of severe fungal infections and parasitic diseases, but its use is limited by its low water solubility and varying bioavailability. New self-emulsifying drug delivery systems (SEDDS) based on PEGylated bile acids (BA-PEGs) were designed and prepared, where the number ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400117m
更新日期:2013-08-05 00:00:00
abstract::Most anticancer drugs are poorly soluble and nonspecific, which restricts their clinical application. Drug conjugates, as a prodrug strategy, provide the possibility to overcome these shortcomings, especially combined with nanotechnology. Drug conjugate nanoparticles possess the advantages of high drug loading capacit...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00631
更新日期:2016-01-04 00:00:00
abstract::Dual variable domain immunoglobulin proteins (DVD-Ig proteins) are large molecules (MW ∼ 200 kDa) with increased asymmetry because of their extended Y-like shape, which results in increased formulation challenges. Liquid-liquid phase separation (LLPS) of protein solutions into protein-rich and protein-poor phases redu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00256
更新日期:2015-09-08 00:00:00
abstract::The wet form of age-related macular degeneration (AMD) is a leading cause of blindness among elderly Americans and is characterized by abnormal vessel growth, termed choroidal neovascularization (CNV). Integrin α5β1 is a transmembrane receptor that binds matrix macromolecules and proteinases to stimulate angiogenesis....
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00056
更新日期:2016-09-06 00:00:00
abstract::Most vaccines contain aluminum adjuvants; however, their exact mechanism of action remains unclear. A novel mechanism by Shi and colleagues proposes aluminum adjuvants may enhance immune activation by binding and reorganizing lipids that are key components of lipid rafts. To better understand the specificity of intera...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00111
更新日期:2016-05-02 00:00:00
abstract::The systemic pharmacokinetics and pharmacodynamics of small molecules are determined by subcellular transport phenomena. Although approaches used to study the subcellular distribution of small molecules have gradually evolved over the past several decades, experimental analysis and prediction of cellular pharmacokinet...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp200092v
更新日期:2011-10-03 00:00:00
abstract::The 1:1 cocrystal of the antifungal agent ketoconazole with p-aminobenzoic acid was successfully crystallized and systematically characterized by a physical and pharmacological point of view. Crystal structure determination confirmed the cocrystal identity, giving full insight in its crystal packing and degree of diso...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01178
更新日期:2020-03-02 00:00:00
abstract::In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape ac...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00015
更新日期:2017-05-01 00:00:00
abstract::The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500662z
更新日期:2015-03-02 00:00:00
abstract::In previous studies, we developed a new technique (ionic gelation vibrational jet flow; IGVJF) in order to encapsulate pancreatic β-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated microcapsules showed good morphology but limited cell functions. Thus, this study aimed to optimize the IGVJF t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00220
更新日期:2017-08-07 00:00:00
abstract::Polycationic polymers like poly(ethylene imine)s (PEIs) are extensively explored for the nonviral transfer of DNA or small RNAs (siRNAs). To enhance biocompatibility and alter pharmacokinetic properties, hyperbranched PEI was recently grafted with the nonligand oligosaccharides maltose or maltotriose at various degree...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400479g
更新日期:2013-12-02 00:00:00
abstract::The human apical sodium-dependent bile acid transporter (hASBT) is a potential target for drug delivery, but an understanding of hASBT substrate requirements is limited. The objective of this study was to evaluate the influence of ionic character and steric bulk in the C-24 region of bile acid conjugates in governing ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp0600135
更新日期:2006-05-01 00:00:00
abstract::Tumor-associated inflammation has been linked to angiogenesis, metastasis and poor prognosis. The 18 kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR), is expressed in activated immune cells such as macrophages, but also in a number of cancer cell lines such as those of breast...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100433c
更新日期:2011-06-06 00:00:00
abstract::This study determined intraluminal ethanol concentrations (stomach and duodenum) in fed healthy volunteers after the consumption of common alcoholic beverages (beer, wine, and whisky). The results of this study were compared with a previous study in fasted volunteers. Five healthy volunteers were recruited in a crosso...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00252
更新日期:2017-12-04 00:00:00
abstract::The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence following standard-of-care therapies, including surgical resection. With most tumors recurring near the site of surgical resection, local delivery of chemotherapy at the time of surgery is a promising strategy. Herein drug-loaded polymer s...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b01114
更新日期:2018-03-05 00:00:00
abstract::"Nano" drug delivery carriers are established technologies for improving the therapeutic index of chemotherapeutic drugs and overcoming formulation challenges of poorly water-soluble compounds. Two important remaining challenges, however, are the need to formulate drugs on a case-by-case basis (due to the specific che...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp5001247
更新日期:2014-06-02 00:00:00
abstract::Current chemotherapy strategies for second-line treatment of relapsed ovarian cancer are unable to effectively treat residual disease post-cytoreduction. The findings presented herein suggest that tissue penetration of drug is not only an issue for large, unresectable tumors, but also for invisible, microscopic lesion...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00426
更新日期:2015-11-02 00:00:00
abstract::Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4002393
更新日期:2013-11-04 00:00:00
abstract::We investigated the effect of polymer composition on nifedipine (NIF) dissolution through molecular-level characterization of NIF/hypromellose (HPMC)/Eudragit S (EUD-S) ternary solid dispersions. The dissolution rates and molecular states of NIF and polymers were evaluated in NIF/HPMC/EUD-S spray-dried samples (SPDs) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00523
更新日期:2018-09-04 00:00:00
abstract::Current experimental methodologies used to determine the thermodynamic solubility of an API within a polymer typically involves establishing the dissolution/melting end point of the crystalline API within a physical mixture or through the use of the glass transition temperature measurement of a demixed amorphous solid...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00445
更新日期:2018-04-02 00:00:00
abstract::The adenovirus (Ad) is widely used as a vaccine because of its ability to induce a cellular and humoral immune response. In addition, human clinical trials have validated the safety and efficacy of Ad as a vaccine vector. The traditional approach for employing the adenovirus as vaccine is to configure the antigen gene...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/acs.molpharmaceut.8b00591
更新日期:2018-12-03 00:00:00
abstract::Novel multivalent copper(II)-conjugated phosphorus dendrimers and their corresponding mononuclear copper(II) complexes were synthesized, characterized, and screened for antiproliferative activity against human cancer cell lines. Selected copper ligands were grafted on the surface of phosphorus dendrimers of generation...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4000184
更新日期:2013-04-01 00:00:00
abstract::Despite holding promise for cancer immunotherapy, the strong pro-inflammatory properties of lipopolysaccharide (LPS) also account for severe localized and systemic side effects, restricting its administrable dosage and the possibility of chronic dosing. Herein, we exploited the surface-active properties of LPS molecul...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00631
更新日期:2019-11-04 00:00:00
abstract::We have identified and characterized a new solid form of trehalose, the δ form (Tδ) using (13)C solid-state NMR spectroscopy (SSNMR). Tδ is formed from dehydrations of trehalose dihydrate (T(h)) performed at or below 100 °C, and it is generated concurrently with the α form of trehalose (Tα) and amorphous trehalose (T(...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400104b
更新日期:2013-09-03 00:00:00
abstract::Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a criti...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100050d
更新日期:2010-08-02 00:00:00
abstract::The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide)...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00195
更新日期:2019-06-03 00:00:00
abstract::5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling acid concentration in the crystallization ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400070a
更新日期:2013-06-03 00:00:00