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      Influence of the Surface Functionalization on the Fate and Performance of Mesoporous Silica Nanoparticles

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          Abstract

          Mesoporous silica nanoparticles have been broadly applied as drug delivery systems owing to their exquisite features, such as excellent textural properties or biocompatibility. However, there are various biological barriers that prevent their proper translation into the clinic, including: (1) lack of selectivity toward tumor tissues, (2) lack of selectivity for tumoral cells and (3) endosomal sequestration of the particles upon internalization. In addition, their open porous structure may lead to premature drug release, consequently affecting healthy tissues and decreasing the efficacy of the treatment. First, this review will provide a comprehensive and systematic overview of the different approximations that have been implemented into mesoporous silica nanoparticles to overcome each of such biological barriers. Afterward, the potential premature and non-specific drug release from these mesoporous nanocarriers will be addressed by introducing the concept of stimuli-responsive gatekeepers, which endow the particles with on-demand and localized drug delivery.

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          Most cited references 379

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          Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism

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            A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

            We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
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              Analysis of nanoparticle delivery to tumours

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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                09 May 2020
                May 2020
                : 10
                : 5
                Affiliations
                [1 ]Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i + 12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
                [2 ]Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
                Author notes
                [* ]Correspondence: migisber@ 123456ucm.es (M.G.-G.); vallet@ 123456ucm.es (M.V.-R.); Tel.: +34-91-394-1843 (M.G.-G. & M.V.-R.)
                Article
                nanomaterials-10-00916
                10.3390/nano10050916
                7279540
                32397449
                © 2020 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/).

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