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      Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

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          Abstract

          Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.

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          Most cited references497

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          Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity (Recommendations 1984)

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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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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                22 January 2021
                February 2021
                : 13
                : 2
                : 143
                Affiliations
                [1 ]Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
                [2 ]Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), 33 El-Behouth St., Dokki 12622, Giza, Egypt
                Author notes
                [* ]Correspondence: k.abouaitah@ 123456labnano.pl (K.A.); w.lojkowski@ 123456labnano.pl (W.L.); Tel.: +48-22-888-0429 or +48-22-632-4302 (K.A. & W.L.); Fax: +48-22-632-4218 (K.A. & W.L.)
                Author information
                https://orcid.org/0000-0001-8413-6738
                https://orcid.org/0000-0001-8521-0688
                Article
                pharmaceutics-13-00143
                10.3390/pharmaceutics13020143
                7912645
                33499150
                4ad509c6-9cdd-4068-991a-0bbc812f7fe1
                © 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/).

                History
                : 30 November 2020
                : 14 January 2021
                Categories
                Review

                mesoporous silica nanoparticles,controlled release,drug delivery systems,anticancer natural prodrugs,natural products,cancer targeting,nanoformulations/nanomedicine applications

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