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

Abstract

(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.

Synthesis of polymer nanogels by electro-Fenton process: investigation of the effect of main operation parameters

“…[19,22,23]. Effective crosslinking of poly(vinylpyrrolidone) (PVP) [22][23][24][25][26], PVP copolymers [9,27,28] and other polymers [29] has been reported. As a major inconvenient, high energy radiation processes are not easily implementable into existing production lines, which limits their large-scale applicability.…”

“…Since the first appearance of this family of nanoscale materials, their application as biocompatible carriers for a large plethora of biomedical and biotechnological applications has been explored [3][4][5]. In particular, these soft materials have gained growing interest for drug delivery because of their high loading capacity and stability [6][7][8][9][10], showing also potential use as pH and temperature sensors [11,12]. They are also employed as in vivo imaging tracers [13], in water treatment [14] and catalysis [15], as smart gating membranes for the fabrication of active photonic crystals and coatings, and for generating bioactive scaffolds in regenerative medicine [16].…”

Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour

“…The average molecular weight of the two variants produced was determined by Zimm plot analysis of static light scattering (SLS) data, the average numbers of carboxyl groups and primary amino groups per nanoparticle were estimated via colorimetric and uorimetric methods, respectively. 18,21 The results are reported in Table 1.…”

“…The functional groups present in the nanogels have been used for the conjugation of several active components: therapeutic molecules such as doxorubicin 20,21 or insulin; 19 targeting moieties like folic acid 21 or antibodies; 22 and chelating groups that can entrap RMI-agents. 23 These results prompted us to test the same type of nanocarriers for AntimiR-31 delivery.…”

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…In drug delivery systems, nanostructures can be injected subcutaneously or intravenously to deliver the loaded drugs to the site of injury or disease with minimum cell toxicity and immune response [ 30 ]. The surface of the drug delivery system can be modified with ligands that can be detected by receptors on the surface of malignant tumours in cancer therapy [ 31 , 32 , 33 , 34 ]. Stimuli-responsive nanostructures have the potential to be used for targeted delivery and controlled drug release.…”