Charge reversal nano-systems for tumor therapy

AbstractSurface charge of biological and medical nanocarriers has been demonstrated to play an important role in cellular uptake. Owing to the unique physicochemical properties, charge-reversal delivery strategy has rapidly developed as a promising approach for drug delivery application, especially for cancer treatment. Charge-reversal nanocarriers are neutral/negatively charged at physiological conditions while could be triggered to positively charged by specific stimuli (i.e., pH, redox, ROS, enzyme, light or temperature) to achieve the prolonged blood circulation and enhanced tumor cellular uptake, thus to potentiate the antitumor effects of delivered therapeutic agents. In this review, we comprehensively summarized the recent advances of charge-reversal nanocarriers, including: (i) the effect of surface charge on cellular uptake; (ii) charge-conversion mechanisms responding to several specific stimuli; (iii) relation between the chemical structure and charge reversal activity; and (iv) polymeric materials that are commonly applied in the charge-reversal delivery systems. Graphical Abstract

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

Nano LIFE ◽

10.1142/s1793984413430034 ◽

2013 ◽

Vol 03 (04) ◽

pp. 1343003 ◽

Cited By ~ 7

Author(s):

BRANDON MATTIX ◽

THOMAS MOORE ◽

OLGA UVAROV ◽

SAMUEL POLLARD ◽

LAUREN O'DONNELL ◽

...

Keyword(s):

Human Brain ◽

Surface Charge ◽

Cellular Uptake ◽

Drug Clearance ◽

Cellular Interaction ◽

Normal Tissues ◽

Poly Ethylene ◽

Uptake Studies ◽

Effect Of Surface

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.

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Effect of Surface Charge on the Cellular Uptake and Cytotoxicity of Fluorescent Labeled Cellulose Nanocrystals

ACS Applied Materials & Interfaces ◽

10.1021/am1006222 ◽

2010 ◽

Vol 2 (10) ◽

pp. 2924-2932 ◽

Cited By ~ 185

Author(s):

Khaled A. Mahmoud ◽

Jimmy A. Mena ◽

Keith B. Male ◽

Sabahudin Hrapovic ◽

Amine Kamen ◽

...

Keyword(s):

Surface Charge ◽

Cellular Uptake ◽

Cellulose Nanocrystals ◽

Effect Of Surface

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Effect of surface charge on the cellular uptake of fluorescent magnetic nanoparticles

Journal of Nanoparticle Research ◽

10.1007/s11051-012-1151-7 ◽

2012 ◽

Vol 14 (10) ◽

Cited By ~ 46

Author(s):

Slavko Kralj ◽

Matija Rojnik ◽

Rok Romih ◽

Marko Jagodič ◽

Janko Kos ◽

...

Keyword(s):

Magnetic Nanoparticles ◽

Surface Charge ◽

Cellular Uptake ◽

Effect Of Surface

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Effect of Surface Charge and Hydrophobicity Modulation on the Antibacterial and Antibiofilm Potential of Magnetic Iron Nanoparticles

Journal of Nanomaterials ◽

10.1155/2017/3528295 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 10

Author(s):

Rania Ibrahim Shebl ◽

Faten Farouk ◽

Hassan Mohamed El-Said Azzazy

Keyword(s):

Surface Charge ◽

Biofilm Formation ◽

E Coli ◽

Inhibitory Potential ◽

Average Size ◽

Positively Charged ◽

Significant Concentration ◽

Effect Of Surface ◽

Antibacterial Potential ◽

Trimethoxy Silane

Unmodified magnetic nanoparticles (MNPs) lack antibacterial potential. We investigated MNPs surface modifications that can impart antibacterial activity. Six MNPs species were prepared and characterized. Their antibacterial and antibiofilm potentials, surface affinity, and cytotoxicity were evaluated. Prepared MNPs were functionalized with citric acid, amine group, amino-propyl trimethoxy silane (APTMS), arginine, or oleic acid (OA) to give hydrophilic and hydrophobic MNPs with surface charge ranging from −30 to +30 mV. Prepared MNPs were spherical in shape with an average size of 6–15 nm. Hydrophobic (OA-MNPs) and positively charged MNPs (APTMS-MNPs) had significant concentration dependent antibacterial effect. OA-MNPs showed higher inhibitory potential againstS. aureusandE. coli(80%) than APTMS-MNPs (70%). Both particles exhibited surface affinity toS. aureusandE. coli.Different concentrations of OA-MNPs decreasedS. aureusandE. colibiofilm formation by 50–90%, while APTMS-MNPs reduced it by 30–90%, respectively. Up to 90% of preformed biofilms ofS. aureusandE. coliwere destroyed by OA-MNPs and APTMS-MNPs. In conclusion, surface positivity and hydrophobicity enhance antibacterial and antibiofilm properties of MNPs.

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