scholarly journals EFFECTS OF POLYMERIC NANOPARTICLE SURFACE PROPERTIES ON INTERACTION WITH BRAIN TUMOR ENVIRONMENT

Nano LIFE ◽  
2013 ◽  
Vol 03 (04) ◽  
pp. 1343003 ◽  
Author(s):  
BRANDON MATTIX ◽  
THOMAS MOORE ◽  
OLGA UVAROV ◽  
SAMUEL POLLARD ◽  
LAUREN O'DONNELL ◽  
...  

Current chemotherapy treatments are limited by poor drug solubility, rapid drug clearance and systemic side effects. Additionally, drug penetration into solid tumors is limited by physical diffusion barriers [e.g., extracellular matrix (ECM)]. Nanoparticle (NP) blood circulation half-life, biodistribution and ability to cross extracellular and cellular barriers will be dictated by NP composition, size, shape and surface functionality. Here, we investigated the effect of surface charge of poly(lactide)-poly(ethylene glycol) NPs on mediating cellular interaction. Polymeric NPs of equal sizes were used that had two different surface functionalities: negatively charged carboxyl ( COOH ) and neutral charged methoxy ( OCH 3). Cellular uptake studies showed significantly higher uptake in human brain cancer cells compared to noncancerous human brain cells, and negatively charged COOH NPs were uptaken more than neutral OCH 3 NPs in 2D culture. NPs were also able to load and control the release of paclitaxel (PTX) over 19 days. Toxicity studies in U-87 glioblastoma cells showed that PTX-loaded NPs were effective drug delivery vehicles. Effect of surface charge on NP interaction with the ECM was investigated using collagen in a 3D cellular uptake model, as collagen content varies with the type of cancer and the stage of the disease compared to normal tissues. Results demonstrated that NPs can effectively diffuse across an ECM barrier and into cells, but NP mobility is dictated by surface charge. In vivo biodistribution of OCH 3 NPs in intracranial tumor xenografts showed that NPs more easily accumulated in tumors with less collagen. These results indicate that a robust understanding of NP interaction with various tumor environments can lead to more effective patient-tailored therapies.

2010 ◽  
Vol 2 (10) ◽  
pp. 2924-2932 ◽  
Author(s):  
Khaled A. Mahmoud ◽  
Jimmy A. Mena ◽  
Keith B. Male ◽  
Sabahudin Hrapovic ◽  
Amine Kamen ◽  
...  

2012 ◽  
Vol 14 (10) ◽  
Author(s):  
Slavko Kralj ◽  
Matija Rojnik ◽  
Rok Romih ◽  
Marko Jagodič ◽  
Janko Kos ◽  
...  

2015 ◽  
Vol 396 (11) ◽  
pp. 1255-1264 ◽  
Author(s):  
Dajana Lichtenstein ◽  
Johanna Ebmeyer ◽  
Patrick Knappe ◽  
Sabine Juling ◽  
Linda Böhmert ◽  
...  

Abstract Because of the rising application of nanoparticles in food and food-related products, we investigated the influence of the digestion process on the toxicity and cellular uptake of silver nanoparticles for intestinal cells. The main food components – carbohydrates, proteins and fatty acids – were implemented in an in vitro digestion process to simulate realistic conditions. Digested and undigested silver nanoparticle suspensions were used for uptake studies in the well-established Caco-2 model. Small-angle X-ray scattering was used to estimate particle core size, size distribution and stability in cell culture medium. Particles proved to be stable and showed radii from 3.6 to 16.0 nm. Undigested particles and particles digested in the presence of food components were comparably taken up by Caco-2 cells, whereas the uptake of particles digested without food components was decreased by 60%. Overall, these findings suggest that in vivo ingested poly (acrylic acid)-coated silver nanoparticles may reach the intestine in a nanoscaled form even if enclosed in a food matrix. While appropriate for studies on the uptake into intestinal cells, the Caco-2 model might be less suited for translocation studies. Moreover, we show that nanoparticle digestion protocols lacking food components may lead to misinterpretation of uptake studies and inconclusive results.


2013 ◽  
Vol 31 (9) ◽  
pp. 1299-1309 ◽  
Author(s):  
Dan-hua Zhou ◽  
Jie Zhang ◽  
Guan Zhang ◽  
Zhi-hua Gan

Biomaterials ◽  
2018 ◽  
Vol 182 ◽  
pp. 104-113 ◽  
Author(s):  
Ji-Long Wang ◽  
Xiao-Jiao Du ◽  
Jin-Xian Yang ◽  
Song Shen ◽  
Hong-Jun Li ◽  
...  

2020 ◽  
Vol 35 ◽  
pp. 100243 ◽  
Author(s):  
Muhammad Usman ◽  
Yumna Zaheer ◽  
Muhammad Rizwan Younis ◽  
Ruken Esra Demirdogen ◽  
Syed Zajif Hussain ◽  
...  

2004 ◽  
Vol 845 ◽  
Author(s):  
Dinesh B. Shenoy ◽  
Jugminder S. Chawla ◽  
Mansoor M. Amiji

1. ABSTRACT: This study was performed to evaluate the in-vitro and in-vivo tumor-cellular uptake and biodistribution pattern of tamoxifen when administered intravenously as a simple solution and upon encapsulation into biodegradable, surface-modified poly(ε-caprolactone) (PCL) nanoparticles. PCL (MW ∼ 15, 000) nanoparticles were prepared by the solvent displacement method and characterized for particle size/charge and surface morphology (by scanning electron microscopy). We investigated the nanoparticle-surface modification potential of the hydrophilic stabilizer (Pluronic® F-68 and F-108) employed during the preparation by electron spectroscopy for chemical analysis (ESCA). Quantitative in-vitro cellular uptake of tritiated (3H) tamoxifen in solution form and as nanoparticulate formulation was assessed in MCF-7 breast cancer cells. In-vivo biodistribution studies for the same formulations were carried out in Nu/Nu mice bearing MDA-MB-231 human breast carcinoma xenograft. Spherical nanoparticles having positive zeta potential (∼25 mV) were obtained in the size range of 200-300 nm. Pluronics (both F-68 and F-108), the triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) induced surface hydrophilization of the nanoparticles via adsorption as evident by ESCA. Nanoparticulate formulations of tamoxifen achieved higher intracellular concentrations when exposed at therapeutic concentrations to tumor cells in-vitro compared to solutions. The in-vivo biodistribution studies carried out in nude mice bearing experimental breast tumor suggested increased tumor concentrations for the drug administered as nanoparticulate formulations besides longer retention times within tumor mass. This type of delivery system is expected to provide better therapeutic benefit by dual means: preferential concentration within the tumor mass via enhanced permeation and retention pathway, and; subsequent controlled release, thus maintaining the local drug concentration for longer periods of time to achieve maximal cell-kill.


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