MULTIFUNCTIONALIZED SPIONs FOR NUCLEAR TARGETING: CELL UPTAKE AND GENE EXPRESSION

NANO ◽  
2014 ◽  
Vol 09 (01) ◽  
pp. 1450009 ◽  
Author(s):  
CHRISTIN M. GRABINSKI ◽  
JATUPORN SALAKLANG ◽  
CAROL M. GARRETT ◽  
AMANDA M. SCHRAND ◽  
ALKE PETRI-FINK ◽  
...  

Superparamagnetic iron oxide nanoparticles (SPIONs) are used in many biological applications, which necessitate intracellular targeting. Here, we investigate intracellular localization and gene expression in HeLa cells after treatment with functionalized SPIONs. Functional groups investigated included positive amino propyl silane (APS), polyethylene glycol and targeting peptides: nuclear targeting peptide (NTP) and/or cancer cell uptake promoting peptide (cRGD). Results revealed that the intracellular localization of SPIONs was strongly dependent on the surface chemistry. Nuclear targeted SPIONs functionalized with only NTP or both NTP and cRGD were mostly localized in perinuclear endosomes with a small fraction entering the nucleus. The biocompatibility of cells after treatment was also dependent on surface chemistry, where SPIONs functionalized with both NTP and cRGD exhibited a more significant reduction of cell proliferation compared to NTP or cRGD individually. Interestingly, gene expression after treatment with SPIONs was similar, regardless of the surface functionalization or intracellular localization. The results of this study showed that cellular uptake and intracellular localization predominantly depended on the surface chemistry, while gene expression exhibited a more generic response to SPION treatment.

2013 ◽  
Vol 49 (spe) ◽  
pp. 15-32 ◽  
Author(s):  
Ali Nazemi ◽  
Elizabeth R. Gillies

A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications.


2021 ◽  
Vol 17 (7) ◽  
pp. 1320-1329
Author(s):  
Thaís Dolzany de Oliveira ◽  
Luiz R. Travassos ◽  
Denise Costa Arruda ◽  
Dayane Batista Tada

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the availablematerials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-β-cyclodextrin. Notably, when peptide C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of PLGA NPs. Therefore, we suggest this peptide as a promising surface modification agent for enhancing drug delivery to cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy.


Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1026
Author(s):  
Elisa Chiodi ◽  
Allison M. Marn ◽  
Matthew T. Geib ◽  
M. Selim Ünlü

The importance of microarrays in diagnostics and medicine has drastically increased in the last few years. Nevertheless, the efficiency of a microarray-based assay intrinsically depends on the density and functionality of the biorecognition elements immobilized onto each sensor spot. Recently, researchers have put effort into developing new functionalization strategies and technologies which provide efficient immobilization and stability of any sort of molecule. Here, we present an overview of the most widely used methods of surface functionalization of microarray substrates, as well as the most recent advances in the field, and compare their performance in terms of optimal immobilization of the bioreceptor molecules. We focus on label-free microarrays and, in particular, we aim to describe the impact of surface chemistry on two types of microarray-based sensors: microarrays for single particle imaging and for label-free measurements of binding kinetics. Both protein and DNA microarrays are taken into consideration, and the effect of different polymeric coatings on the molecules’ functionalities is critically analyzed.


Processes ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 82
Author(s):  
Helmut Thissen ◽  
Richard A. Evans ◽  
Vincent Ball

In recent years major advances in surface chemistry and surface functionalization have been performed through the development, most often inspired by living organisms, of versatile methodologies. Among those, the contact of substrates with aminomalononitrile (AMN) containing solutions at pH = 8.5 allows a conformal coating to be deposited on the surface of all known classes of material. Since AMN is a molecule probably formed in the early atmosphere of our planet and since HCN-based compounds have been detected on many comets and Titan (Saturn’s largest moon) it is likely that such molecules will open a large avenue in surface functionalization mostly for bio-applications. This mini review describes the state of the art of AMN-based coatings from their deposition kinetics, composition, chemical reactivity, hypothetical structure to their first applications as biomaterials. Finally, the AMN-based versatile coatings are compared to other kinds of versatile coating based on catecholamines and polyphenols.


2010 ◽  
Vol 426 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Richard W. P. Smith ◽  
Nicola K. Gray

Cytoplasmic PABP [poly(A)-binding protein] is a multifunctional protein with well-studied roles in mRNA translation and stability. In the present review, we examine recent evidence that the activity of PABP is altered during infection with a wide range of viruses, bringing about changes in its stability, complex formation and intracellular localization. Targeting of PABP by both RNA and DNA viruses highlights the role of PABP as a central regulator of gene expression.


2003 ◽  
Vol 427 (1-2) ◽  
pp. 201-207 ◽  
Author(s):  
C. Dahmen ◽  
A. Janotta ◽  
D. Dimova-Malinovska ◽  
S. Marx ◽  
B. Jeschke ◽  
...  

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