25 research outputs found
Dendrimer conjugates for light-activated delivery of antisense oligonucleotides
PAMAM dendrimer conjugates are used to co-deliver oligonucleotides and photosensitizers to cancer cells. After photo-irradiation, substantial reporter eGFP expression is produced by functional delivery of a model oligonucleotide
In vitro and in vivo antitumor properties of 7-epidocetaxel, a major impurity of docetaxel
Purpose: To investigate the antitumor properties and toxicity of 7-epi docetaxel (7-epi DTX) as an active pharmaceutical ingredient, and in formulations.Methods: Docetaxel-loaded albumin nanoparticles (DTX NPs) were prepared by freeze-drying, while 7- epi DTX was detected and isolated by high performance liquid chromatography (HPLC). Their antitumor properties were evaluated in vitro in CT26 cells and in vivo in BALB/c sk-ov-3 xenograft nude mice model. The tissues were histological examined.Results: The in vivo antitumor effects of DTX NPs at different doses of 7-epi DTX were similar. Moreover, the in vitro anti-cancer effect of 7-epi DTX was comparable to that of DTX. However, the in vivo antitumor effectiveness of 7-epi DTX was inferior to that of DTX. In toxicity studies, 7-epi DTX did not elicit any acute toxic effects both as active pharmaceutical ingredients, and as a component of formulations.Conclusion: The results indicate that 7-epi DTX does not elicit acute toxic effects both as an active pharmaceutical ingredient and in bulk formulations. The antitumor property of 7-epi DTX is less than that of DTX.Keywords: 7-Epidocetaxel, Impurity, Antitumor properties, Toxicit
Direct oligonucleotide–photosensitizer conjugates for photochemical delivery of antisense oligonucleotides
Direct conjugation of photosensitizer to oligonucleotides allows spatial and temporal co-localization of the two modalities in the target cells and thus leads to superior photochemical delivery of oligonucleotides
Dendritic nanoconjugates for intracellular delivery of neutral oligonucleotides
Conjugation of neutral oligonucleotides (ONs) with PAMAM dendrimers resulted in ultra-small nanoconjugates that combine superior ON delivery and reduced cytotoxicity
Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy
Abstract Application of photodynamic therapy for treating cancers has been restrained by suboptimal delivery of photosensitizers to cancer cells. Nanoparticle (NP)-based delivery has become an important strategy to improve tumor delivery of photosensitizers; however, the success is still limited. One problem for many NPs is poor penetration into tumors, and thus the photokilling is not complete. We aimed to use chemical conjugation method to engineer small NPs for superior cancer cell uptake and tumor penetration. Thus, Chlorin e6 (Ce6) was covalently conjugated to PAMAM dendrimer (generation 7.0) that was also modified by tumor-targeting RGD peptide. With multiple Ce6 molecules in a single nanoconjugate molecule, the resultant targeted nanoconjugates showed uniform and monodispersed size distribution with a diameter of 28 nm. The singlet oxygen generation efficiency and fluorescence intensity of the nanoconjugates in aqueous media were significantly higher than free Ce6. Targeted nanoconjugates demonstrated approximately 16-fold enhancement in receptor-specific cellular delivery of Ce6 into integrin-expressing A375 cells compared to free Ce6 and thus were able to cause massive cell killing at low nanomolar concentrations under photo-irradiation. In contrast, they did not cause significant toxicity up to 2 μM in dark. Due to their small size, the targeted nanoconjugates could penetrate deeply into tumor spheroids and produced strong photo-toxicity in this 3-D tumor model. As a result of their great cellular delivery, small size, and lack of dark cytotoxicity, the nanoconjugates may provide an effective tool for targeted photodynamic therapy of solid tumors. Graphical abstrac
Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy
Cuartas Jornadas de Extensión Odontológica y cuarto encuentro de jóvenes extensionistas
Voluntariado Universitario
Museo - “El lugar de la Historia y la Memoria”
Prosecretaría de Asuntos Estudiantiles y Recursos Humanos
Dirección de Politicas Sociales
Expo Universidad 2019 - “Encontrá lo que querés ser”
Dirección de Cultura
ADEI - Articulación Docencia Extensión e Investigación
ADEI VIAJES - Articulación Docencia Extensión e Investigación
Laboratorio de Impresión 3D
Carrera de Especialización en Odontología Social y Comunitaria
Odontología, facultad cardio asistida
Programa RecuperamosFacultad de Odontologí
NIR Light-Activated Drug Release for Synergetic Chemo–Photothermal Therapy
Nanocarriers
like PEGylated liposomes have achieved enhanced drug accumulation
in tumors and reduced systemic side effects, but failed to actively
release the carried drug into cancer cells. To obtain improved therapeutic
efficacy, we designed a novel liposome that was inserted by the amphiphilic
agent PEG-IR780-C13 (PIC-Lipo) and encapsulated therapeutic agent
doxorubicin (DOX), termed as DOX@PIC-Lipo. Upon NIR laser irradiation,
the novel liposomes could generate hyperthermia and facilitate the
release of encapsulated DOX from PIC-Lipo, which were confirmed by
photothermal curves and the DOX release assay <i>in vitro</i>, respectively. In addition, the enhanced DOX release and sufficient
hyperthermia have performed synergetic therapeutic efficacy both <i>in vitro</i> and <i>in vivo</i>. Therefore, DOX@PIC-Lipo
might provide an active strategy to release the loaded drug for synergetic
chemo–photothermal combined therapy