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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8003534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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