Abstract：
PURPOSE:To compare the effectiveness of trastuzumab-modified gold nanoparticles (AuNP) labeled with 177Lu (trastuzumab-AuNP-177Lu) targeted to HER2 with non-targeted AuNP-177Lu for killing HER2-overexpressing breast cancer (BC) cells in vitro and inhibiting tumor growth in vivo following intratumoral (i.t.) injection. METHODS:AuNP (30 nm) were modified with polyethylene glycol (PEG) polymers linked to trastuzumab or to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators to complex 177Lu. The binding and internalization of trastuzumab-AuNP-177Lu in HER2-positive SK-BR-3, BT-474 and MDA-MB-361 human BC cells were studied. Clonogenic survival and DNA double-strand breaks (DSBs) were measured after exposure of SK-BR-3 or MDA-MB-361 cells to trastuzumab-AuNP-177Lu or AuNP-177Lu. NOD/SCID mice with s.c. MDA-MB-361 tumor xenografts were treated by i.t. injection of 3 MBq (0.15 mg) of trastuzumab-AuNP-177Lu, AuNP-177Lu or normal saline. Tumor growth was measured over 16 days and normal tissue toxicity evaluated. RESULTS:Trastuzumab-AuNP-177Lu was bound and internalized by HER2 positive BC cells (KD = 7.6 ± 2.0 nM). Trastuzumab-AuNP-177Lu was 42.9 and 2.6-fold more effective than AuNP-177Lu at decreasing the clonogenic survival of SK-BR-3 (1.3 × 106 HER2/cell) and MDA-MB-361 (5.1 × 105 HER2/cell) cells, respectively, exposed overnight to these agents (1.5 nM; 20 MBq/mg Au). Under the same treatment conditions, 10-fold and 2.8-fold more DNA DSBs were observed in SK-BR-3 and MDA-MB-361 cells, respectively, exposed to trastuzumab-AuNP-177Lu than AuNP-177Lu. Trastuzumab-AuNP-177Lu was 1.8-fold more effective at inhibiting tumor growth than AuNP-177Lu. No or minimal normal tissue toxicity was observed for trastuzumab-AuNP-177Lu or AuNP-177Lu treatments. CONCLUSION:Trastuzumab-AuNP-177Lu enables an efficient local radiation treatment of HER2-positive BC.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Cai Z,Yook S,Lu Y,Bergstrom D,Winnik MA,Pignol JP,Reilly RMdoi
10.1007/s11095-016-2082-2subject
Has Abstractpub_date
2017-03-01 00:00:00pages
579-590issue
3eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-016-2082-2journal_volume
34pub_type
杂志文章abstract：PURPOSE:The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm, a new transdermal delivery system of buprenorphine, was evaluated. METHODS:Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation potential were determined by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9470-6
更新日期：2008-05-01 00:00:00
abstract：:To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015826229323
更新日期：1990-03-01 00:00:00
abstract：PURPOSE:Microphysiological systems (MPS), also known as "organs-on-chips" or "tissue chips," leverage recent advances in cell biology, tissue engineering, and microfabrication to create in vitro models of human organs and tissues. These systems offer promising solutions for modeling human physiology and disease in vitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-019-2742-0
更新日期：2019-12-17 00:00:00
abstract：PURPOSE:The aim of this work was to investigate the influence of the oily nucleus composition on physico-chemical properties and anesthetic activity of poly (lactide-co-glycolide) nanocapsules with benzocaine. METHODS:Nanocapsules containing benzocaine were prepared with three different oily nucleus composition and ch...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0425-6
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:To study the influence of cytotoxicity of macromolecules, VEGF gene expression, and vascular permeability on the enhanced permeability and retention (EPR) effect. METHODS:Mice bearing xenografts of A2780 multidrug resistant human ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2-hydroxypropyl)m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007500412442
更新日期：2000-05-01 00:00:00
abstract：PURPOSE:This study was conducted to demonstrate the use of differential scanning calorimetry (DSC) in detecting and measuring beta-relaxation processes in amorphous pharmaceutical systems. METHODS:DSC was employed to study amorphous samples of poly(vinylpyrrolidone) (PVP), indomethacin (IM), and ursodeoxycholic acid (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9044-4
更新日期：2006-02-01 00:00:00
abstract：:Primaquine (I), a 6-methoxy-8-aminoqumoline derivative used for the treatment of malaria has previously been shown to be metabolized to 8-(3-carboxy-l-methyl-propylamino)-6-methoxyquinoline by both micro-organisms and laboratory rats. Reported herein is the synthesis of this novel metabolite. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016311616719
更新日期：1984-03-01 00:00:00
abstract：PURPOSE:To improve upon the theory of reasoned action and apply it to pharmaceutical research, we investigated the effects of relevant appraisals attributes, and past behavior of physicians on the use of drug information sources. We also examined the moderating effects of practice characteristics. METHODS:A mail quest...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012143915886
更新日期：1997-10-01 00:00:00
abstract：:Loracarbef is an oral 1-carba-1-dethiacephalosporin antibiotic structurally related to cefaclor. Like many beta-lactam antibiotics, loracarbef exists in several hydrated crystalline forms. The pH-solubility profile curve for loracarbef monohydrate is U-shaped, resembling those of other zwitterionic cephalosporins. Lor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018949709797
更新日期：1992-02-01 00:00:00
abstract：:A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018929531410
更新日期：1993-04-01 00:00:00
abstract：PURPOSE:Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. METHODS:Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2453-y
更新日期：2018-07-03 00:00:00
abstract：PURPOSE:Knowledge about the uptake mechanism and subsequent intracellular routing of non-viral gene delivery systems is important for the development of more efficient carriers. In this study we compared two established cationic polymers pDMAEMA and PEI with regard to their transfection efficiency and mechanism of cell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9287-3
更新日期：2007-08-01 00:00:00
abstract：PURPOSE:The study was performed for clarifying the mechanism of interaction between indoxyl sulfate (IS), a typical uremic toxin bound to site II, and site I-ligands when bound to human serum albumin (HSA). The effect of the N to B transition on the interactions was also examined. METHODS:Quantitative investigation of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011014629551
更新日期：2001-04-01 00:00:00
abstract：BACKGROUND:With the recent approval of the first small interfering RNA (siRNA) therapeutic formulated as nanoparticles, there is increased incentive for establishing the factors of importance for the design of stable solid dosage forms of such complex nanomedicines. METHODS:The aims of this study were: (i) to identify...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2663-y
更新日期：2019-08-02 00:00:00
abstract：OBJECTIVES:We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9499-6
更新日期：2008-05-01 00:00:00
abstract：:Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. T...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015852732512
更新日期：1992-04-01 00:00:00
abstract：:Indomethacin microspheres based on a combination of ethylcellulose and polyethyleneglycol were prepared using the solvent evaporation process. Release profiles of ensemble and individual microspheres were measured. Both were found to follow first-order kinetics, in contrast to what was expected. This was attributed to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015917023949
更新日期：1988-03-01 00:00:00
abstract：PURPOSE:The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS:Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharm...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007657109012
更新日期：2000-12-01 00:00:00
abstract：PURPOSE:The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells. METHODS:The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7096-0
更新日期：2005-10-01 00:00:00
abstract：:Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015902308676
更新日期：1990-12-01 00:00:00
abstract：PURPOSE:The aim was to investigate the influence of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations, as indicators of stability, of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone) (PVP). METHODS:Amorphous lactose and composite partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1024462306941
更新日期：2003-07-01 00:00:00
abstract：:Sulfasalazine, 60 mg/kg, was administered orally to groups of rats (n = 4) along with 1, 5, or 10 mg/kg of riboflavin. Plasma and urine were assayed for 5-aminosalicylic acid, acetyl-5-aminosalicylic acid, sulfapyridine, and acetyl-sulfapyridine using an HPLC method. The mean percent of dose recovered as total metabol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015938706685
更新日期：1989-12-01 00:00:00
abstract：PURPOSE:Overexpression of hyaluronan (HA) receptors on cancer cells results in enhanced endocytotic uptake of the drug conjugate. An N-(2-hydroxypropyl)methacrylamide (HPMA)-HA polymeric drug delivery system was used for targeted delivery of doxorubicin to cancer cells. METHODS:HA-doxorubicin (DOX) bioconjugates (HA-D...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015170907274
更新日期：2002-04-01 00:00:00
abstract：:Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018956516640
更新日期：1992-01-01 00:00:00
abstract：PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8815-2
更新日期：2006-01-01 00:00:00
abstract：PURPOSE:The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy. METHODS:Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0275-7
更新日期：2010-12-01 00:00:00
abstract：PURPOSE:To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide. METHODS:The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Cir...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1298-2
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:Recombinant human platelet glycoprotein Ibalpha-immunoglobulin G1 chimeric proteins (GPIbalpha-Ig) have varying levels of anti-thrombotic activities based on their ability to compete for platelet mediated adhesion to von Willebrand Factor (vWF). Valine substituted GPIbalpha-Ig chimeras, at certain position, inc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9018-1
更新日期：2006-08-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the delivery of itraconazole (ITZ) particles to a murine lung model by nebulization. METHODS:Three ITZ formulations were prepared and characterized in the dry state using contact angle, dissolution, X-ray powder diffraction, scanning electron microscopy, and Brunaue...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9904-6
更新日期：2006-05-01 00:00:00
abstract：PURPOSE:To study the pulmonary absorption and tolerability of various formulations of the decapeptide cetrorelix acetate in rats by a new aerosol delivery system (ASTA-ADS) for intratracheal application. METHODS:Using the ASTA-ADS, cetrorelix liquid formulations (aqueous solutions for ultrasonic nebulization) were fir...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011028227155
更新日期：2001-06-01 00:00:00
