Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acryli...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2016-11, Vol.21 (11), p.1594-1594
Main Authors: Adamo, Giorgia, Grimaldi, Natascia, Campora, Simona, Bulone, Donatella, Bondì, Maria Luisa, Al-Sheikhly, Mohamad, Sabatino, Maria Antonietta, Dispenza, Clelia, Ghersi, Giulio
Format: Article
Language:English
Subjects:
Animals
Antioxidants - chemistry
Antioxidants - pharmacology
Cancer therapies
Cell Line, Tumor
Doxorubicin - pharmacology
Drug delivery systems
Drugs
Folic Acid - chemistry
Folic Acid - metabolism
Folic Acid Transporters - antagonists & inhibitors
HeLa Cells
Humans
Metabolism
Metabolites
Mice
Nanoparticles
Nanoparticles - chemistry
Neoplasms - drug therapy
Neoplasms - metabolism
NIH 3T3 Cells
Oxidation-Reduction - drug effects
Particle Size
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacology
Polyethyleneimine - chemistry
Polyethyleneimine - pharmacology
Povidone - chemistry
Povidone - pharmacology
Radiation
RNA, Small Interfering - pharmacology
Toxicity
Vitamin B
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Summary:(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules21111594