Multivalent polyrotaxane vectors as adaptive cargo complexes for gene therapy

Ardeleanu, Rodinel; Dascalu, Andrei; Neamţu, Andrei; Peptanariu, Dragos; Uritu, Cristina M.; Maier, Stelian Sergiu; Nicolescu, Alina; Simionescu, Bogdan C.; Barboiu, Mihail; Pinteala, Mariana

doi:10.1039/c7py01256j

Cited by 23 publications

(23 citation statements)

References 77 publications

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“…Different strategies for surface functionalization of AuNPs using a wide range of ligands have been done to overcome these limitations. Polyethylene glycol (PEG) is the polymer known as the most popular material for surface modification in various types of nanoparticulate drugs or gene delivery systems [9][10][11][12][13] . The coverage of the conjugates with PEG moieties plays a major role in improving solubility and stability in aqueous media of the carriers, prolonging the circulation time in the blood stream, bypassing immune recognition due to steric hindrance mechanism [14][15][16] .…”

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Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells

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Pricop

Uritu

et al. 2020

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The paper aims to investigate the cytotoxic effect on tumor cells of irradiated AuNPs in green light and subsequently functionalized with HS-PEG-NH 2. The toxicity level of gold conjugates after their functionalization with DOX and TAT peptide was also evaluated. The AuNPs were prepared using the modified Turkevich method and exposed to visible light at a wavelength of 520 nm prior their PEGylation. The optical properties were analyzed by UV-vis spectroscopy, the surface modification was investigated using FTIR and XPS spectroscopies and their sizes and morphologies were evaluated by TEM and DLS techniques. DOX and TAT peptide were linked to the surface of PEGylated AuNPs by reacting their amino groups with glycidyloxypropyl of PEGylated DOX or TAT conjugates under mild conditions at room temperature and in the presence of ethanol as catalyst. The conjugates containing DOX or DOX and TAT have been characterized by fluorescence and FTIR techniques. The changes of electrochemical features were observed using cyclic voltammetry, suggesting a better stability of irradiated nanoparticles. By mass spectrometry it was confirmed that the compounds of interest were obtained. The cell viability test showed that irradiated and non-irradiated nanoparticles coated with PEG are not toxic in normal cells. Tumor cell viability analysis showed that the PEGylated nanoparticles modified with DOX and TAT peptide were more effective than pristine DOX, indicating cytotoxicity up to 10% higher than non-irradiated ones. The presence of gold nanomaterials (AuNPs) in biomedicine and particularly in antitumor therapy still remains a topic of wide debate, as evidenced by the tremendous amount of scientific works on this issue in recent years 1-3. An impressive number of research studies have straightened their efforts toward the use of AuNPs in enhancing the efficiency of cancer treatment, due to their ease production and chemical functionalization of their surface 4,5. Gold nanoparticles are feasible to be developed as versatile nontoxic carriers for drug release as long as they are able to be conjugated with different molecules, including chemotherapeutics, antibodies, peptides, ligands, and other structures which are likely to promote a great capacity to penetrate the tumor site, resulting in a predominant accumulation of bioactive agent in the tumor region 6,7. On the other hand, the passive anticancer effect based on the accumulation strategy of AuNPs at the tumor site is limited by the inherent heterogeneities of tumor vasculature 8. It was shown that nanoparticle concentration in the target tissue is influenced by renal clearance rate, and also by activation of immune system mechanisms such as opsonization or nonspecific particle phagocytosis, fulfilled by the reticuloendothelial system (RES).

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confidence: 99%

Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells

Lupușoru

Pricop

Uritu

et al. 2020

Sci Rep

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“…Such functional aggregates are dynamic (bio)conjugates that encompass a minimum number of molecular motifs to satisfy the required polyvalent biological tasks. They operate based on the mutual supramolecular affinity and dynamical steric complementary between the inactive (vector) and active (nucleic segment) complements [109].…”

Section: Polymeric Non-viral Vectors For Gene Deliverymentioning

confidence: 99%

Smart Supra- and Macro-Molecular Tools for Biomedical Applications

2020

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Stimuli-responsive, “smart” polymeric materials used in the biomedical field function in a bio-mimicking manner by providing a non-linear response to triggers coming from a physiological microenvironment or other external source. They are built based on various chemical, physical, and biological tools that enable pH and/or temperature-stimulated changes in structural or physicochemical attributes, like shape, volume, solubility, supramolecular arrangement, and others. This review touches on some particular developments on the topic of stimuli-sensitive molecular tools for biomedical applications. Design and mechanistic details are provided concerning the smart synthetic instruments that are employed to prepare supra- and macro-molecular architectures with specific responses to external stimuli. Five major themes are approached: (i) temperature- and pH-responsive systems for controlled drug delivery; (ii) glycodynameric hydrogels for drug delivery; (iii) polymeric non-viral vectors for gene delivery; (iv) metallic nanoconjugates for biomedical applications; and, (v) smart organic tools for biomedical imaging.

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“…К сожалению, в настоящее время практически отсутствуют публикации, посвященные силатрансодержащим полимерам, а в немногих имеющихся публикациях по данной тематике [6][7][8] не рассматривается биологическая активность полученных макромолекул. В то же время можно ожидать, что введение силатранового фрагмента в полимеры позволит получить новые био-логически активные полимерные системы, а исследование взаимосвязи свойств этих систем и особенностей строения полимеров сделает возможным получение макромолекулярных систем с заданными физико-химическими и биоактивными свойствами.…”

Section: Abstract: Poly(methylmethacrylates) Copolymers Silatranesunclassified

“…На первой стадии получали низкомолекулярный 3-метакрилоксипропилсилатран конденсацией 3-метакрилоксипропилтриэтоксисилана с триэтаноламином. Синтез проводили вариацией описанной в [6] методики: к смеси триэтаноламина (15.0 мл, 16.8 г, 0.11 моль) с бензолом (30 мл) добавляли каталитическое количество (5 мг) металлического натрия, после чего смесь выдерживали при 80 °С в течение 1 ч. Затем к реакционной смеси добавляли раствор эквивалентного количества (27.3 г, 0.11 моль) метакрилоксипропилтриэтоксисилана в бензоле (20 мл), и проводили синтез силатрана в течение 18 ч c азеотропной отгонкой смеси бензола и этанола, одновременно прибавляя к реакционной смеси аналогичное отогнанному количество сухого бензола. После окончания реакции бензол отгоняли при пониженном давлении, реакционную массу растворяли в 20 мл тетрагидрофурана и переосаждали в гептане, декантируя выпавший силатран.…”

Section: схемаunclassified

Silatrane-Containing Polymethacrylates

et al. 2019

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The possibility of synthesizing silatrane-containing polymers was investigated using three different synthetic methods: the formation of silatrane fragments from polymers with trialkoxysilyl groups, the copolymerization of silatrane-containing monomers, and the reaction of silatranes with functional copolymers. The obtained polymethacrylate copolymers were characterized using gel permeation chromatography, IR and NMR spectroscopy. It was shown that depending on the synthesis scheme used, polymers were obtained in the form of three-dimensional structures or soluble products. It was established that the molecular weight of the synthesized polymers depended significantly on both the content of silatrane fragments and the synthesis technique used. It was shown that the modification of linear carboxyl-containing copolymers by silatranes allows the synthesis of high-molecular polymers with a high content of silatrane fragments. For the synthesized polymers, thermal properties were investigated, and the hydrophobicity of the surface of polymer films was also evaluated. It was found that all the studied polymers did not have clear melting and crystallization temperatures. The polymers were stable in an inert atmosphere up to 270-280 °C, whereas in air they decomposed at lower temperatures with the restructuring of the macromolecular skeleton and the formation of highly heat-resistant silicone structures. An increase in the content of silatrane moieties in the copolymers led to an increase in the hydrophilicity of polymers.

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Multivalent polyrotaxane vectors as adaptive cargo complexes for gene therapy

Abstract: The philosophy to design and construct polyrotaxane carriers, as efficient gene delivery systems.

Cited by 23 publications

References 77 publications

Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells

Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells

Smart Supra- and Macro-Molecular Tools for Biomedical Applications

Silatrane-Containing Polymethacrylates

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