Designing Mesoporous Silica Nanoparticles to Overcome Biological Barriers by Incorporating Targeting and Endosomal Escape.

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Gisbert Garzarán, Miguel and Lozano Borregón, Daniel and Matsumoto, Kotaro and Komcatsu, Aoi and Manzano García, Miguel and Tamanoi, Fuyuhiko and Vallet Regí, María (2021) Designing Mesoporous Silica Nanoparticles to Overcome Biological Barriers by Incorporating Targeting and Endosomal Escape. ACS Applied Materials & Interfaces . ISSN 1944-8244 (In Press)

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Official URL: https://dx.doi.org/10.1021/acsami.0c21507




Abstract

The several biological barriers that nanoparticles might encounter when administered to a patient constitute the major bottleneck of nanoparticle7 mediated tumor drug delivery, preventing their successful translation into the clinic and reducing their therapeutic profile. In this work, mesoporous silica nanoparticles have been employed as a platform to engineer a versatile nanomedicine able to address such barriers, achieving (a) excessive premature drug release control, (b) accumulation in tumor tissues, (c) selective internalization in tumoral cells, and (d) endosomal escape. The nanoparticles have been decorated with a self-immolative redox-responsive linker to prevent excessive premature release, to which a versatile and polyvalent peptide that is able to recognize tumoral cells and induce the delivery of the nanoparticles to the cytoplasm via endosomal escape has been grafted. The excellent biological performance of the carrier has been demonstrated using 2D and 3D in vitro cell cultures and a tumor-bearing chicken embryo model, demonstrating in all cases high biocompatibility and cytotoxic effect, efficient endosomal escape and tumor penetration, and accumulation in tumors grown on the chorioallantoic membrane of chicken embryos.


Item Type:Article
Additional Information:

RESEARCH ID  S-2443-2016  (Miguel Gisbert Garzarán)
ORCID 0000-0001-9815-0354 (Miguel Gisbert Garzarán)
RESEARCH ID B-5081-2017  (Daniel Lozano Borregón)
ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón)
RESEARCH ID K-3719-2014  (Miguel Manzano García)
ORCID 0000-0001-6238-6111 (Miguel Manzano García)
RESEARCHER ID M-3378-2014 (María Vallet Regí)
ORCID 0000-0002-6104-4889 (María Vallet Regí)

Uncontrolled Keywords:mesoporous silica nanoparticles, stimuli-responsive, drug delivery, redox-responsive, self-immolative, targeting, endosomal escape, chicken embryo model
Subjects:Sciences > Chemistry > Materials
ID Code:63979
Deposited On:15 Feb 2021 12:55
Last Modified:14 Jan 2022 12:25

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