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Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA g...

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Autores principales: Cavallaro, Gennara, Sardo, Carla, Craparo, Emanuela Fabiola, Giammona, Gaetano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003534/
https://www.ncbi.nlm.nih.gov/pubmed/33808586
http://dx.doi.org/10.3390/molecules26061713
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author Cavallaro, Gennara
Sardo, Carla
Craparo, Emanuela Fabiola
Giammona, Gaetano
author_facet Cavallaro, Gennara
Sardo, Carla
Craparo, Emanuela Fabiola
Giammona, Gaetano
author_sort Cavallaro, Gennara
collection PubMed
description Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin.
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spelling pubmed-80035342021-03-28 Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy Cavallaro, Gennara Sardo, Carla Craparo, Emanuela Fabiola Giammona, Gaetano Molecules Article Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin. MDPI 2021-03-19 /pmc/articles/PMC8003534/ /pubmed/33808586 http://dx.doi.org/10.3390/molecules26061713 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cavallaro, Gennara
Sardo, Carla
Craparo, Emanuela Fabiola
Giammona, Gaetano
Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title_full Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title_fullStr Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title_full_unstemmed Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title_short Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
title_sort development of new targeted inulin complex nanoaggregates for sirna delivery in antitumor therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003534/
https://www.ncbi.nlm.nih.gov/pubmed/33808586
http://dx.doi.org/10.3390/molecules26061713
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