Multifunctional drug nanocarriers formed by cRGD-conjugated βCD-PAMAM-PEG for targeted cancer therapy

Saraswathy, Manju; Knight, Gavin; Pilla, Srikanth; Ashton, Randolph S.; Gong, Shaoqin

doi:10.1016/j.colsurfb.2014.12.042

Cited by 39 publications

(18 citation statements)

References 64 publications

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“…In addition, Dox-encapsulated nanoparticles formed by poly(RGD- co -β-amino ester) and Dox-polymeric nanoparticles functionalized with RGD had higher cytotoxicity than nanoparticles prepared without RGD in U87MG cells [ 24 ]. Besides these, in recent years, other authors have described the improvement in transport of Dox into tumor cells with targeting of RGD-nanoparticles using different materials and methods of preparation [ 37 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

et al. 2017

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Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG.

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Section: Discussionmentioning

confidence: 99%

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

et al. 2017

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“…24 The Arg-Gly-Asp (RGDyC) is selective to α v β 3 integrin peptides and can also combine with integrin receptors on the surface of leukocytes (neutrophils and monocytes). 25,26 It has been found that both α v β 3 and α v β 5 integrins are expressed on glioma cells and vasculature. 27,28 It provides an ideal strategy for targeted delivery.…”

Section: Introductionmentioning

confidence: 99%

A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system

Han

Zheng

et al. 2018

IJN

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BackgroundThe Traditional Chinese Medicine, arsenic trioxide (ATO, As2O3) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo.PurposeThe objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment.MethodsThe targeting drug carrier (RGDyC-mPEG-PAMAM) was synthesized based on Arg-Gly-Asp (RGDyC) and αvβ3 integrin targeting ligand, and conjugated to PEGylated fifth generation polyamidoamine dendrimer (mPEG-PAMAM). It was characterized by nuclear magnetic resonance, fourier transform infrared spectra, Nano-particle size-zeta potential analyzer,etc. The in vitro release characteristics were studied by dialysis bag method. MTT assay was used to investigate the cytotoxicity of carriers and the antitumor effect of ATO formulation. In vitro blood-brain barrier (BBB) and C6 cell co-culture models were established to investigate the inhibitory effect of different ATO formulation after transporting across BBB. Pharmacokinetic and antitumor efficacy studies were investigated in an orthotopic murine model of C6 glioma.ResultsThe prepared RGDyC-mPEG-PAMAM was characterized for spherical dendrites, comparable size (21.60±6.81 nm), and zeta potential (5.36±0.22 mV). In vitro release showed that more ATO was released from RGDyC-mPEG-PAMAM/ATO (79.5%) at pH 5.5 than that of pH 7.4, during 48 hours. The cytotoxicity of PEG-modified carriers was lower than that of the naked PAMAM on both human brain microvascular endothelial cells and C6 cells. In in vitro BBB model, modification of RGDyC heightened the cytotoxicity of ATO loaded on PAMAM, due to an increased uptake by C6 cells. The results of cell cycle and apoptosis analysis revealed that RGDyC-mPEG-PAMAM/ATO arrested the cell cycle in G2-M and exhibited threefold increase in percentage of apoptosis to that in the PEG-PAMAM/ATO group. Compared with ATO-sol group, both RGDyC-mPEG-PAMAM/ATO and mPEG-PAMAM/ATO groups prolonged the half-life time, increased area under the curve, and improved antitumor effect, significantly. While the tumor volume inhibitory of RGDyC-mPEG-PAMAM/ATO was 61.46±12.26%, it was approximately fourfold higher than the ATO-sol group, and twofold to the mPEG-PAMAM/ATO group.ConclusionIn this report, RGDyC-mPEG-PAMAM could enhance the antitumor of ATO to glioma, it provides a desirable strategy for targeted therapy of glioma.

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“…To quantify cumulative drug released at each time point, the absorbance of collected aliquots was assessed at 485 nm wavelength using a plate reader, and compared to a DOX standard curve. 29, 64 Peak absorbance of DOX in PBS (pH 7.4) was previously confirmed to be 485 nm when assessed using an absorbance spectral sweep from 300–700 nm at 1 mg/mL concentration (Supplemental Figure 1). …”

Section: Methodsmentioning

confidence: 73%

Anticancer Therapeutic Alginate-Based Tissue Sealants for Lung Repair

Fenn

Charron

Oldinski

2017

ACS Appl. Mater. Interfaces

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Injury to the connective tissue that lines the lung, the pleura, or to the lung itself can occur from many causes including trauma or surgery, as well as lung diseases or cancers. To address current limitations for patching lung injuries, to stop air or fluid leaks, an adherent hydrogel sealant patch system was developed, based on methacrylated alginate (AMA) and AMA di-aldehyde (AMA-DA) blends, which is capable of sealing damaged tissues and sustaining physiological pressures. Methacrylation of alginate hydroxyl groups rendered the polysaccharide capable of photo-crosslinking when mixed with an eosin Y-based photo-initiator system, and exposed to visible green light. Oxidation of alginate yields functional aldehyde groups capable of imine bond formation with proteins found in many tissues. The alginate-based patch system was rigorously tested on a custom burst pressure testing device. Blending of non-oxidized material with oxidized (aldehyde modified) alginates yielded patches with improved burst pressure performance, and decreased delamination as compared with pure AMA. Human mesothelial cell (MeT-5A) viability and cytotoxicity were retained when cultured with the hydrogel patches. The release and bioactivity of doxorubicin-encapsulated sub-microspheres enabled the fabrication of drug-eluting adhesive patches, and were effective in decreasing human lung cancer cell (A549) viability.

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Multifunctional drug nanocarriers formed by cRGD-conjugated βCD-PAMAM-PEG for targeted cancer therapy

Cited by 39 publications

References 64 publications

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

A novel RGDyC/PEG co-modified PAMAM dendrimer-loaded arsenic trioxide of glioma targeting delivery system

Anticancer Therapeutic Alginate-Based Tissue Sealants for Lung Repair

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