Abstract:
:The successful applicability of gene therapy approaches will heavily rely on the development of efficient and safe nonviral gene delivery vectors, for example, cell-penetrating peptides (CPPs). CPPs can condense oligonucleotides and plasmid DNA (pDNA) into nanoparticles, thus allowing the transfection of genetic material into cells. However, despite few promising attempts, CPP-mediated pDNA delivery has been relatively inefficient due to the unfavorable nanoparticle characteristics or the nanoparticle entrapment to endocytic compartments. In many cases, both of these drawbacks could be alleviated by modifying CPPs with a stearic acid residue, as demonstrated in the delivery of both the pDNA and the short oligonucleotides. In this study, PepFect14 (PF14) peptide, previously used for the transport of shorter oligonucleotides, is demonstrated to be suited also for the delivery of pDNA. It is shown that PF14 forms stable nanoparticles with pDNA with a negative surface charge and size of around 130-170 nm. These nanoparticles facilitate efficient gene delivery and expression in a variety of regular adherent cell lines and also in difficult-to-transfect primary cells. Uptake studies indicate that PF14/pDNA nanoparticles are utilizing class A scavenger receptors (SCARA) and caveolae-mediated endocytosis as the main route for cellular internalization. Conclusively, PF14 is an efficient nonviral vector for gene delivery.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Veiman KL,Mäger I,Ezzat K,Margus H,Lehto T,Langel K,Kurrikoff K,Arukuusk P,Suhorutšenko J,Padari K,Pooga M,Lehto T,Langel Üdoi
10.1021/mp3003557subject
Has Abstractpub_date
2013-01-07 00:00:00pages
199-210issue
1eissn
1543-8384issn
1543-8392journal_volume
10pub_type
杂志文章abstract::The Flory-Huggins interaction parameter has been shown to be useful in predicting the thermodynamic miscibility of a polymer and a small molecule in a binary mixture. In the present paper, this concept was extended and evaluated to determine whether or not the Flory-Huggins interaction parameter can be applied to smal...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp900304p
更新日期:2010-06-07 00:00:00
abstract::Diagnostic imaging of the liver by ultrasound, computed tomography (CT) and magnetic resonance tomography (MRT) is generally limited to the visualization of the morphology. In order to exploit the intriguing liver tropism of the human hepatitis B virus (HBV) for molecular imaging of the liver, peptidic tracers derived...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400038r
更新日期:2013-06-03 00:00:00
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::"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::Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a rece...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200122w
更新日期:2011-06-06 00:00:00
abstract::It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX)....
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00717
更新日期:2018-11-05 00:00:00
abstract::Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)n, G5-(MFCO-MTX)n were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)n, D-(MFCO-MTX)n. The monomer G5-(COG-MTX)n conjugates exhibited only a weak, rapidly reversible binding...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500608s
更新日期:2014-11-03 00:00:00
abstract::Understanding protein stability is central to combatting protein aggregation diseases and developing new protein therapeutics. At the high concentrations often present in biological systems, purified proteins can exhibit undesirable high solution viscosities and poor solubilities mediated by short-range electrostatic ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00322
更新日期:2017-10-02 00:00:00
abstract::Plant or microbial lectins are known to exhibit potent antiviral activities against viruses with glycosylated surface proteins, yet the mechanism(s) by which these carbohydrate-binding proteins exert their antiviral activities is not fully understood. Hepatitis C virus (HCV) is known to possess glycosylated envelope p...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400399b
更新日期:2013-12-02 00:00:00
abstract::In the present age of pharmaceutical research and development, focused delivery of decision making data is more imperative than ever before. Resulting from several years' success, failure and consequential learning, this article also proffers advice and guidance on which in vitro and in vivo experiments to perform to ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300476z
更新日期:2013-04-01 00:00:00
abstract::The pharmacological exploitation of resveratrol is hindered by rapid phase-II conjugative metabolism in enterocytes and hepatocytes. One approach to the solution of this problem relies on prodrugs. We report the synthesis and characterization as well as the assessment of in vivo absorption and metabolism of a set of p...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400226p
更新日期:2013-07-01 00:00:00
abstract::Dry powder inhalations (DPI) of microparticles containing isoniazid (INH) and rifabutin (RFB) are under preclinical development for use in pulmonary tuberculosis. Microparticles containing 0.25, 2.5, or 25 mg of each drug were administered daily for 90 days to rhesus macaques (n = 4/group). Single inhalations or intra...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300043f
更新日期:2012-04-02 00:00:00
abstract::Targeted therapies are emerging as a preferred strategy for treatment of cancer and other diseases. To evaluate the effect of high affinity receptors on the rate and extent of tumor penetration of receptor-targeted drugs, we have characterized the kinetics of folate-rhodamine uptake by folate receptor (FR)-expressing ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp900158d
更新日期:2009-11-01 00:00:00
abstract::Cancer is a leading cause of death within developed nations, and part of this morbidity is due to difficulties associated with its treatment. Currently, anticancer therapy relies heavily upon the administration of small molecule cytotoxic drugs that attack both cancerous and noncancerous cells due to limited selectivi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp2005966
更新日期:2012-03-05 00:00:00
abstract::Recent studies on aqueous supersaturated lipophilic drug solutions prepared by methods including antisolvent addition, pH swing, or dissolution of amorphous solid dispersions (ASDs) have demonstrated that when crystallization is slow, these systems undergo liquid-liquid phase separation (LLPS) when the concentration o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00202
更新日期:2016-06-06 00:00:00
abstract::The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targete...
journal_title:Molecular pharmaceutics
pub_type: 临床试验,杂志文章
doi:10.1021/acs.molpharmaceut.7b00095
更新日期:2017-08-07 00:00:00
abstract::Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors sug...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00339
更新日期:2018-09-04 00:00:00
abstract::Curcumin (CUR) is a unique natural compound with promising anticancer and anti-inflammatory activities. However, the therapeutic efficacy of curcumin was challenged in clinical trials, mostly due to its low bioavailability, rapid metabolism, and elimination. We designed a nanodrug form of curcumin, which makes it stab...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500290f
更新日期:2014-09-02 00:00:00
abstract::Lipid-core nanocapsules (LCNs) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCNs carry the drug through the blood-brain barrier or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00875
更新日期:2016-04-04 00:00:00
abstract::Fluid bed coating has been shown to be a suitable manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug-polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01023
更新日期:2017-04-03 00:00:00
abstract::Therapeutic monoclonal antibody (mAb) candidates that form highly viscous solutions at concentrations above 100 mg/mL can lead to challenges in bioprocessing, formulation development, and subcutaneous drug delivery. Earlier studies of mAbs with concentration-dependent high viscosity have indicated that mAbs with negat...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500485w
更新日期:2015-01-05 00:00:00
abstract::We report on tailored lipid-polymer hybrid nanoparticles (NPs) delivering nitric oxide (NO) under the control of visible light as a tool for overcoming doxorubicin (DOX) resistance. The NPs consist of a polymeric core and a coating. They are appropriately designed to entrap DOX in the poly(lactide-co-glycolide) core a...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00290
更新日期:2020-06-01 00:00:00
abstract::In this work, we investigated the relationship between various intermolecular hydrogen-bonding (H-bonding) interactions and the miscibility of the model hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP) across an entire composition range of solid dispersions prepared by quasi-equilibriu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3003495
更新日期:2012-11-05 00:00:00
abstract::Ultrasound-targeted microbubble destruction (UTMD) is a promising technique to facilitate the delivery of chemotherapy in cancer treatment. However, the process typically uses nonspecific microbubbles, leading to low tumor-to-normal tissue uptake ratio and adverse side effects. In this study, we synthesized the LHRH r...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400523h
更新日期:2014-01-06 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::Some of the most significant therapeutic leads and agents used for the treatment of cancer target microtubule dynamics. Paclitaxel is an exceptional example that is currently used for treating a wide range of tumors. New, non-taxane microtubule stabilizers, including several epothilones, are advancing through clinical...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp060016h
更新日期:2006-07-01 00:00:00
abstract::5P12-RANTES is a recently developed chemokine analogue that has shown high level protection from SHIV infection in macaques. However, the feasibility of using 5P12-RANTES as a long-term HIV prevention agent has not been explored partially due to the lack of available delivery devices that can easily be modified for lo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3007242
更新日期:2013-10-07 00:00:00
abstract::The effect of tertiary butyl alcohol (TBA) as a cosolvent on the phase behavior of mannitol in frozen and freeze-dried systems was characterized using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD; laboratory and synchrotron sources). Solutions of mannitol (2 and 5% w/w) in TBA-water systems of...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00492
更新日期:2020-08-03 00:00:00
abstract::Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO)...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp9001393
更新日期:2010-02-01 00:00:00
abstract::Electrostatic potential (ESP) is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as prediction of likely sites of electrophilic and nucleophilic metabolic attack. Knowledge of sites of metabolic attack is of paramount importance in DMPK resear...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3004385
更新日期:2013-04-01 00:00:00