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1.
J Am Chem Soc ; 142(22): 10184-10197, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32368907

RESUMO

In addition to the already described ligand L4a, two pyclen-based lanthanide chelators, L4b and L4c, bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [EuL4a], [SmL4a], [YbL4b], [TbL4c], and [DyL4c]. Additionally, the symmetrically arranged regioisomer L4a' was also synthesized as well as its [EuL4a'] complex to highlight the astonishing positive impact of the dissymmetrical N-distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications. Each presents high brightness, quantum yields, and lifetimes. Staining of the complexes into living human breast cancer cells was observed. In addition, in vivo two-photon microscopy was performed for the first time on a living zebrafish model with [EuL4a]. No apparent toxicity was detected on the growth of the zebrafish, and images of high quality were obtained.

2.
J Cell Mol Med ; 23(9): 6499-6503, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31293082

RESUMO

In the search of a better enzyme therapy in Pompe disease, the conjugation of mannose 6-phosphonates to the recombinant enzyme appeared as an enhancer of its efficacy. Here, we demonstrated that the increased efficacy of the conjugated enzyme is partly due to a higher intracellular maturation because of its insensitiveness to acid phosphatases during the routing to lysosomes.

3.
Int J Mol Sci ; 20(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181759

RESUMO

The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs.


Assuntos
Fotoquimioterapia/métodos , Neoplasias da Próstata/metabolismo , Receptor IGF Tipo 2/metabolismo , Linhagem Celular Tumoral , Endocitose , Humanos , Masculino , Manosefosfatos/administração & dosagem , Manosefosfatos/química , Manosefosfatos/farmacologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Dióxido de Silício/química
4.
Chemistry ; 25(38): 9026-9034, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30972809

RESUMO

Two trispicolinate 1,4,7-triazacyclonane (TACN)-based ligands bearing three picolinate biphotonic antennae were synthetized and their Yb3+ and Gd3+ complexes isolated. One series differs from the other by the absence (L1 )/presence (L2 ) of bromine atoms on the antenna backbone, offering respectively improved optical and singlet-oxygen generation properties. Photophysical properties of the ligands, complexes and micellar Pluronic suspensions were investigated. Complexes exhibit high two-photon absorption cross-section combined either with NIR emission (Yb) or excellent 1 O2 generation (Gd). The very large intersystem crossing efficiency induced by the combination of bromine atom and heavy rare-earth element was corroborated with theoretical calculations. The 1 O2 generation properties of L2 Gd micellar suspension under two-photon activation leads to tumour cell death, suggesting the potential of such structures for theranostic applications.

5.
Chemistry ; 25(14): 3637-3649, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30620107

RESUMO

The synthesis and the photophysical properties of a new class of fully organic monodisperse nanoparticles for combined two-photon imaging and photodynamic therapy are described. The design of such nanoparticles is based on the covalent immobilization of a dedicated quadrupolar dye that combines excellent two-photon absorbing (2PA) properties, fluorescence and singlet oxygen generation ability, in a phosphorous-based dendrimeric architecture. First, a bifunctional quadrupolar dye bearing two different grafting moieties, a phenol function and an aldehyde function, was synthesized. It was then covalently grafted through its phenol function to a phosphorus-based dendrimer scaffold of generation 1. The remaining aldehyde functions were then used to continue the dendrimer synthesis up to generation 2, introducing finally 24 water-solubilizing triethyleneglycol chains at its periphery. A dendrimer confining 12 photoactive quadrupolar units in its inner scaffold and showing water solubility was thus obtained. Interestingly, the G1 and G2 dendrimers retain some fluorescence as well as significant singlet oxygen production efficiencies while they were found to show very high 2PA cross-sections in a broad range of the NIR biological spectral window. Hydrophilic dendrimer G2 was tested in vitro on breast cancer cells, first in one- and two-photon microscopy, which allowed for visualization of their cell internalization, then in two-photon photodynamic therapy. While being nontoxic in the dark and, more importantly, under exposure to daylight, dendrimer G2 proved to be a very efficient cell-death inducer only under two-photon irradiation in the NIR.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Dendrímeros/farmacologia , Corantes Fluorescentes/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/química , Feminino , Corantes Fluorescentes/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Imagem Óptica/métodos , Fotoquimioterapia/métodos , Fótons , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica/métodos
6.
Biomimetics (Basel) ; 3(3)2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31105244

RESUMO

Careful analysis of any new nanomedicine device or disposal should be undertaken to comprehensively characterize the new product before application, so that any unintended side effect is minimized. Because of the increasing number of nanotechnology-based drugs, we can anticipate that regulatory authorities might adapt the approval process for nanomedicine products due to safety concerns, e.g., request a more rigorous testing of the potential toxicity of nanoparticles (NPs). Currently, the use of mesoporous silica nanoparticles (MSN) as drug delivery systems is challenged by a lack of data on the toxicological profile of coated or non-coated MSN. In this context, we have carried out an extensive study documenting the influence of different functionalized MSN on the cellular internalization and in vivo behaviour. In this article, a synthesis of these works is reviewed and the perspectives are drawn. The use of magnetic MSN (Fe3O4@MSN) allows an efficient separation of coated NPs from cell cultures with a simple magnet, leading to results regarding corona formation without experimental bias. Our interest is focused on the mechanism of interaction with model membranes, the adsorption of proteins in biological fluids, the quantification of uptake, and the effect of such NPs on the transcriptomic profile of hepatic cells that are known to be readily concerned by NPs' uptake in vivo, especially in the case of an intravenous injection.

7.
J Control Release ; 269: 15-23, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29108866

RESUMO

Pompe disease is a rare disorder due to deficiency of the acid α-glucosidase (GAA) treated by enzyme replacement therapy. The present authorized treatment with rhGAA, the recombinant human enzyme, provides an important benefit in the infantile onset; however, the juvenile and adult forms of the disease corresponding to >80% of the patients are less responsive to this treatment. This resistance has been mainly attributed to an insufficiency of mannose 6-phosphate residues in rhGAA to address lysosomes through the cation-independent mannose 6-phosphate receptor (CI-M6PR). As yet, several attempts to improve the enzyme delivery by increasing the number of mannose 6-phosphate on the enzyme were poorly effective on the late onset form of the disease. Here, we show that chemical conjugation of a synthetic analogue of the mannose 6-phosphate, named AMFA, onto rhGAA improves the affinity for CI-M6PR and the uptake of the enzyme in fibroblasts and myoblasts of adult Pompe patients. More importantly, only the conjugated rhGAA-AMFA was effective in aged Pompe mice when compared to rhGAA. Weekly treatment with 5-20mg·kg-1 rhGAA-AMFA provided major improvements of the motor function and of the myofiber structure, whereas rhGAA was inactive. Finally, AMFA addition did not induce supplementary immune response to the enzyme. This modified enzyme, displaying a muscle recovery in aged Pompe mice that was never attained before, could be considered as a potential therapy for the late onset Pompe disease.


Assuntos
Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Manosefosfatos/administração & dosagem , alfa-Glucosidases/administração & dosagem , Adulto , Animais , Células Cultivadas , Fibroblastos/metabolismo , Glicogênio/metabolismo , Doença de Depósito de Glicogênio Tipo II/metabolismo , Humanos , Manosefosfatos/química , Camundongos Knockout , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismo
8.
Nanoscale ; 9(43): 16622-16626, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29082396

RESUMO

Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles (BSPOR and BSPHT) were prepared. Their endocytosis in MCF-7 cancer cells was shown with two-photon excited fluorescence (TPEF) imaging. With two-photon excited photodynamic therapy (TPE-PDT), BSPOR was more phototoxic than BSPHT, which in contrast displayed a very high signal for photoacoustic imaging in mice.

9.
Chembiochem ; 18(21): 2110-2114, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-28863239

RESUMO

Different intracellular delivery systems of bioactive compounds have been developed, including cell-penetrating peptides. Although usually nontoxic and biocompatible, these vectors share some of the general drawbacks of peptides, notably low bioavailability and susceptibility to protease degradation, that limit their use. Herein, the conversion of short peptide sequences into poly-α-amino-γ-lactam foldamers that adopt a ribbon-like structure is investigated. This template is used to distribute critical cationic and/or hydrophobic groups on both sides of the backbone, leading to potent short, cell-permeable foldamers with a low positive-charge content. The lead compound showed dramatically improved protease resistance and was able to efficiently deliver a biologically relevant cargo inside cells. This study provided a simple strategy to convert short peptide sequences into efficient protease-resistant cell-penetrating foldamers.


Assuntos
Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos , Lactamas/farmacocinética , Polímeros/farmacocinética , Linhagem Celular Tumoral , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lactamas/química , Estrutura Molecular , Polímeros/química
10.
Nanomaterials (Basel) ; 7(7)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28665317

RESUMO

The biological fate of nanoparticles (NPs) for biomedical applications is highly dependent of their size and charge, their aggregation state and their surface chemistry. The chemical composition of the NPs surface influences their stability in biological fluids, their interaction with proteins, and their attraction to the cell membranes. In this work, core-shell magnetic mesoporous silica nanoparticles (Fe3O4@MSN), that are considered as potential theranostic candidates, are coated with polyethylene glycol (PEG) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. Their biological fate is studied in comparison to the native NPs. The physicochemical properties of these three types of NPs and their suspension behavior in different media are investigated. The attraction to a membrane model is also evaluated using a supported lipid bilayer. The surface composition of NPs strongly influences their dispersion in biological fluids mimics, protein binding and their interaction with cell membrane. While none of these types of NPs is found to be toxic on mice four days after intravenous injection of a dose of 40 mg kg-1 of NPs, their surface coating nature influences the in vivo biodistribution. Importantly, NP coated with DMPC exhibit a strong accumulation in liver and a very low accumulation in lung in comparison with nude or PEG ones.

11.
Angew Chem Int Ed Engl ; 55(47): 14774-14777, 2016 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-27774736

RESUMO

Improving therapeutics delivery in enzyme replacement therapy (ERT) for lysosomal storage disorders is a challenge. Herein, we present the synthesis of novel analogues of mannose 6-phosphate (M6P), known as AMFAs and functionalized at the anomeric position for enzyme grafting. AMFAs are non-phosphate serum-resistant derivatives that efficiently bind the cation-independent mannose 6-phosphate receptor (CI-M6PR), which is the main pathway to address enzymes to lysosomes. One of the AMFAs was used to improve the treatment of the lysosomal myopathy Pompe disease, in which acid α-glucosidase (GAA) is defective. AMFA grafting on a M6P-free recombinant GAA led to a higher uptake of the GAA in adult Pompe fibroblasts in culture as compared to Myozyme, the M6P recombinant GAA. Moreover, the treatment of Pompe adult mice with the AMFA-grafted recombinant enzyme led to a remarkable improvement, even at low doses, in muscle functionality and regeneration, whereas Myozyme had limited efficacy.


Assuntos
Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Lisossomos/enzimologia , Manosefosfatos/farmacologia , alfa-Glucosidases/metabolismo , Animais , Configuração de Carboidratos , Desenho de Fármacos , Doença de Depósito de Glicogênio Tipo II/metabolismo , Humanos , Lisossomos/metabolismo , Manosefosfatos/síntese química , Manosefosfatos/química , Camundongos
12.
Oncol Rep ; 36(2): 1127-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27373750

RESUMO

Although antiestrogens significantly improve the survival of patients with ER-positive breast cancer, therapeutic resistance remains a major limitation. The combinatorial use of antiestrogen with other therapies was proposed to increase their efficiency and more importantly, to prevent or delay the resistance phenomenon. In the present study, we addressed their combined effects with proteasome inhibitors (PIs). The effects of antiestrogens (hydroxyl-tamoxifen, raloxifen and fulvestrant) currently used in endocrine therapy were tested in combination with PIs, bortezomib or MG132, on the growth of three ER-positive breast cancer cell lines and in two cellular models of acquired antiestrogen resistance. When compared to single treatments, these combined treatments were significantly more effective in preventing the growth of the cell lines. The regulation of key cell cycle proteins, the cyclin-dependent kinase inhibitors, p21WAF1 and p27KIP1, were also studied. Bortezomib and MG132 drastically increased p21WAF1 expression through elevation of its mRNA concentration. Notably, p27KIP1 regulation was quite different from that of p21WAF1. Furthermore, the effect of bortezomib in combination with antiestrogen was evaluated on antiestrogen-resistant cell lines. The growth of two antiestrogen-resistant cell lines appeared responsive to proteasome inhibition and was strongly decreased by a combined therapy with an antiestrogen. Collectively, these findings provide new perspectives for the use of PIs in combination with endocrine therapies for breast cancer and possibly to overcome acquired hormonal resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/metabolismo , Receptores Estrogênicos/metabolismo , Bortezomib/administração & dosagem , Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinases Ciclina-Dependentes/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Moduladores de Receptor Estrogênico/administração & dosagem , Feminino , Fulvestranto , Humanos , Leupeptinas/administração & dosagem , Células MCF-7 , Inibidores de Proteassoma/administração & dosagem , RNA Mensageiro/metabolismo , Cloridrato de Raloxifeno/administração & dosagem , Tamoxifeno/administração & dosagem
13.
Front Mol Biosci ; 3: 1, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26870736

RESUMO

Three dimensional sub-micron resolution has made two-photon nanomedicine a very promising medical tool for cancer treatment since current techniques cause significant side effects for lack of spatial selectivity. Two-photon-excited (TPE) photodynamic therapy (PDT) has been achieved via mesoporous nanoscaffolds, but the efficiency of the treatment could still be improved. Herein, we demonstrate the enhancement of the treatment efficiency via gold-mesoporous organosilica nanocomposites for TPE-PDT in cancer cells when compared to mesoporous organosilica particles. We performed the first comparative study of the influence of the shape and spatial position of gold nanoparticles (AuNPs) with mesoporous silica nanoparticles (MSN) functionalized with thiol groups and doped with a two-photon electron donor (2PS). The resulting multifunctional nanocarriers displayed TPE-fluorescence and were imaged inside cells. Furthermore, mesoporous organosilica NPs decorated gold nanospheres (AuNSs) induced 63 percent of selective killing on MCF-7 breast cancer cells. This study thus provides insights for the design of more effective multifunctional two-photon-sensitive nanocomposites via AuNPs for biomedical applications.

14.
ChemMedChem ; 11(3): 302-8, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26639308

RESUMO

Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac-arg-O2 Oc-(Val)3-Sta-Ala-Sta-(AMPA)4-NH2; O2 Oc=8-amino-3,6-dioxaoctanoyl, Sta=statine, AMPA=ortho-aminomethylphenylacetyl], containing a new kind of cell-penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure-activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action.


Assuntos
Aminoácidos Aromáticos/farmacologia , Antineoplásicos/farmacologia , Catepsina D/antagonistas & inibidores , Pepstatinas/farmacologia , Inibidores de Proteases/farmacologia , Aminoácidos Aromáticos/química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Pepstatinas/química , Inibidores de Proteases/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
16.
Nanoscale ; 7(26): 11444-52, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26083979

RESUMO

The synthesis of mesoporous silica nanoparticles bearing organic functionalities is strained by the careful adjustment of the reaction parameters, as the incorporation of functional and/or voluminous organosilanes during the sol-gel synthesis strongly affects the final structure of the nanoparticles. In this paper we describe the design of new clickable mesoporous silica nanoparticles as spheres or rods, synthesized by the co-condensation of TEOS with two clickable organosilanes (bearing alkyne and azide groups) and readily multi-functionalizable by CuAAC click chemistry. We show that controlled loadings of clickable functions can be homogeneously distributed within the MSN, allowing us to efficiently click-graft various pairs of functionalities while preserving the texture and morphology of the particles. The homogeneous distribution of the grafted functionalities was probed by FRET experiments between two anchored fluorophores. Moreover, a communication by proton transfer between two functions was demonstrated by constructing a light-actuated nanomachine that works through a proton transfer between a photoacid generator and a pH-sensitive supramolecular nanogate. The activation of the nanomachine enabled the successful release of rhodamine B in buffered solutions and the delivery of doxorubicin in breast cancer cells (MCF-7) upon blue irradiation.


Assuntos
Nanopartículas/química , Prótons , Dióxido de Silício , Química Click/métodos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Dióxido de Silício/síntese química , Dióxido de Silício/química
17.
Angew Chem Int Ed Engl ; 54(20): 5952-6, 2015 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-25802144

RESUMO

The development of personalized and non-invasive cancer therapies based on new targets combined with nanodevices is a major challenge in nanomedicine. In this work, the over-expression of a membrane lectin, the cation-independent mannose 6-phosphate receptor (M6PR), was specifically demonstrated in prostate cancer cell lines and tissues. To efficiently target this lectin a mannose-6-phosphate analogue was synthesized in six steps and grafted onto the surface of functionalized mesoporous silica nanoparticles (MSNs). These MSNs were used for in vitro and ex vivo photodynamic therapy to treat prostate cancer cell lines and primary cell cultures prepared from patient biopsies. The results demonstrated the efficiency of M6PR targeting for prostate cancer theranostic.


Assuntos
Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Receptor IGF Tipo 2/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Humanos , Masculino , Manosefosfatos/síntese química , Manosefosfatos/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Tamanho da Partícula , Fotoquimioterapia , Porosidade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptor IGF Tipo 2/genética , Dióxido de Silício/química , Propriedades de Superfície
18.
Small ; 11(3): 295-9, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25208237

RESUMO

A two-photon photosensitizer with four triethoxysilyl groups is synthesized through the click reaction. This photosensitizer allows the design of bridged silsesquioxane (BS) nanoparticles through a sol-gel process; moreover, gold core BS shells or BS nanoparticles decorated with gold nanospheres are synthesized. An enhancement of the two-photon properties is noted with gold and the nanoparticles are efficient for two-photon imaging and two-photon photodynamic therapy of cancer cells.


Assuntos
Diagnóstico por Imagem , Ouro , Nanopartículas , Neoplasias/diagnóstico , Neoplasias/terapia , Compostos de Organossilício , Fotoquimioterapia , Fótons , Compostos de Amônio Quaternário , Triazóis , Sobrevivência Celular , Fluorescência , Humanos , Células MCF-7 , Nanopartículas/ultraestrutura , Solubilidade , Espectrometria de Fluorescência
19.
Adv Mater ; 26(45): 7643-8, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25323443

RESUMO

Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect.


Assuntos
Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Silício/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Endocitose/efeitos dos fármacos , Endocitose/efeitos da radiação , Humanos , Raios Infravermelhos , Células MCF-7 , Manose/química , Manose/uso terapêutico , Microscopia Confocal , Microscopia de Fluorescência , Nanopartículas/química , Fótons , Fármacos Fotossensibilizantes/química , Porosidade , Porfirinas/química , Silício/química
20.
Chemistry ; 20(30): 9372-80, 2014 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-24986399

RESUMO

Mesoporous silica nanoparticles (MSNPs) are functionalized with molecular-recognition sites by anchoring a triazine or uracil fragment on the surface. After loading these MSNPs with dyes (propidium iodide or rhodamine B) or with a drug (camptothecin, CPT) they are capped by the complementary fragments, uracil and adenine, respectively, linked to the bulky cyclodextrin ring. These MSNPs are pH-sensitive and indeed, the dye release was observed at acidic pH by continuously monitored fluorescence spectroscopy studies. On the other hand, no dye leakage occurred at neutral pH, hence meeting the non-premature requirement to minimize side effects. In vitro studies were performed and confocal microscopy images demonstrate the internalization of the MSNPs and also dye release in the cells. To investigate the drug-delivery performance, the cytotoxicity of CPT-loaded nanoparticles was tested and cell death was observed. A remarkably lower amount of loaded CPT in the MSNPs (more than 40 times less) proved to be as efficient as free CPT. These results not only demonstrate the drug release after pore opening under lysosomal pH, but they also show the potential use of these MSNPs to significantly decrease the amount of the administered drug.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Microscopia Confocal/métodos , Nanopartículas/administração & dosagem , Dióxido de Silício/administração & dosagem , Triazinas/química , Uracila/química
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