Complexes of Dendrimers with Bovine Serum Albumin

Mandeville, J. S.; Tajmir-Riahi, H.A.

doi:10.1021/bm9011979

Cited by 214 publications

(118 citation statements)

References 53 publications

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“…Meanwhile, β‐sheet content increased from 6.4% to 8%, which was associated with the increment of random coil content. Therefore, the binding of C‐GNRs induced unfolding of hemoglobin and the loss of a large part of helical stability, resulting in polypeptide chain extension 17, 32. Based on the findings described earlier, it could be deduced that the binding of C‐GNRs caused extensive conformational changes in hemoglobin, and the protein adapted its structural content during the interaction process.…”

Section: Resultsmentioning

confidence: 79%

Hematological Effects of Gold Nanorods on Erythrocytes: Hemolysis and Hemoglobin Conformational and Functional Changes

et al. 2017

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Gold nanorods (GNRs) are a unique class of metal nanostructures that have attractive potentials in biomedical applications, and the concern on their biological safety is concomitantly increasing. Hemocompatibility is extremely important as their contact with blood circulation is unavoidable during in vivo delivery. Herein, two kinds of GNRs coated with hexadecyltrimethylammonium bromide (C‐GNRs) or poly(sodium‐p‐styrenesulfonate) are used to test their potential toxicological effects in blood. C‐GNRs with positive surface charges efficiently induce hemolysis when encountering erythrocytes. Cellular internalization of C‐GNRs is found, and they subsequently bind with hemoglobin, forming bioconjugates. The interaction between hemoglobin and C‐GNR (stoichiometry 32.7:1) is regulated by electrostatic forces. Chromophores like tryptophan (Trp) are found to interact with C‐GNRs, causing enhancement in fluorescence intensity. The conformation of protein is partially altered, evidenced by decrease in α‐helical, increase in β‐sheet and random coil of hemoglobin. Although C‐GNRs do not essentially decrease oxygen binding capacity of hemoglobin, they hamper oxygen release from the protein. Heme, the oxygen binding unit, releases from hemoglobin upon C‐GNR treatment, which could contribute to C‐GNR‐induced hemolysis. This study demonstrates the hematological effects of GNRs, revealing their potential risk in biomedical applications.

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Section: Resultsmentioning

confidence: 79%

Hematological Effects of Gold Nanorods on Erythrocytes: Hemolysis and Hemoglobin Conformational and Functional Changes

et al. 2017

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“…However, we can make an assumption that an excess of dendrimers' positive charges is crucial for the effective transfection, not only due to promoted cell entry, but is also related to the interactions with serum proteins. Positively charged dendrimers tend to associate with serum proteins, including serum albumins [48][49][50] and regulatory proteins [51,52]. On one hand, this can reduce dendrimers' cytotoxicity since their surface functional groups might be shielded by proteins.…”

Section: Discussionmentioning

confidence: 99%

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Ihnatsyeu-Kachan

Dzmitruk

Apartsin

et al. 2017

Colloids and Interfaces

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Currently, RNAi based approaches for cancer treatment involving short double stranded RNA molecules (siRNA) are under vigorous scrutinization. Due to numerous biological obstacles, siRNA delivery into target cells requires protective escort. On the other hand, combining of siRNA-mediated gene silencing and action of conventional chemotherapeutics can propose additional enhancement of anticancer activity. In the present study, we investigated a siRNA cocktail able to downregulate anti-apoptotic genes (BCL-xL, BCL-2, MCL-1) and the chemotherapeutic agent 5-fluorouracil (5-FU) to evaluate multi-target cytotoxic effect on human cervical carcinoma cells (HeLa cell line). Novel phosphorus containing dendrimers of 3rd and 4th generations (namely AE2G3 and AE2G4) with voluminous piperidine terminal cationic groups were designed and tested as siRNA carriers. Dendrimers of both generations showed remarkable ability to bind pro-apoptotic siRNAs and provided 80-100% siRNA uptake by HeLa cells in the serum containing medium, while the widespread transfection agent Lipofectamine showed only~40% uptake. SiRNA cocktail (in low concentrations 50 and 100 nM) delivered by AE2G3 dendrimer caused almost complete elimination of cancer cells. We have discovered considerable increase of 5-FU cytotoxic effect by addition of AE2G3/siRNA cocktail complexes in low doses. Thus, we demonstrated the effectiveness of combined multi-target siRNA anticancer approach and described new highly effective serum stable nanomaterial vehicle for gene-based drugs.

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“…The binding strength between dendrimer-guest complexes has been determined by isothermal titration calorimetry(ITC) [26][27][28][29], high performance liquid chromatography (HPLC) [30] and fluorescence spectroscopy [31][32][33]. Detailed conformations of dendrimers interacting with guest molecules have been studied by nuclear magnetic resonance(NMR) [34][35][36] and the size of the dendrimer-guest complexes has been measured by dynamic light scattering (DLS) [22,31].…”

Section: Introductionmentioning

confidence: 99%

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Kim

Lamm

2012

Polymers

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Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM) dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed.

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Complexes of Dendrimers with Bovine Serum Albumin

Cited by 214 publications

References 53 publications

Hematological Effects of Gold Nanorods on Erythrocytes: Hemolysis and Hemoglobin Conformational and Functional Changes

Hematological Effects of Gold Nanorods on Erythrocytes: Hemolysis and Hemoglobin Conformational and Functional Changes

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

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