Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery

Abstract Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility ( 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems

Lipid-oligonucleotide conjugates improve cellular uptake and efficiency of TCTP-antisense in castration-resistant prostate cancer

International audienceTranslationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression. However, the intracellular delivery and silencing activity of these oligonucleotides remains a challenge, and depend on the use of transfection agents and delivery systems. Here we show that lipid-modified ASO (LASOs) has improved penetration and efficiency in inhibiting TCTP expression in the absence of additional transfection agents, both in vitro and in vivo. Transfection with TCTP-LASO led to rapid and prolonged internalization via macropinocytosis, TCTP downregulation and significant decreased cell viability. We also show that lipid-modification led to delayed tumor progression in CRPC xenografts models, with no significant toxic effects observed

Electropolymerizable Thiophene-Oligonucleotides for Electrode Functionalization

Inserting complex biomolecules such as oligonucleotides during the synthesis of polymers remains an important challenge in the development of functionalized materials. In order to engineer such a biofunctionalized interface, a single-step method for the covalent immobilization of oligonucleotides (ONs) based on novel electropolymerizable lipid thiophene-oligonucleotide (L-ThON) conjugates was employed. Here, we report a new thiophene phosphoramidite building block for the synthesis of modified L-ThONs. The biofunctionalized material was obtained by direct electropolymerization of L-ThONs in the presence of 2,2′-bithiophene (BTh) to obtain a copolymer film on indium tin oxide electrodes. In situ electroconductance measurements and microstructural studies showed that the L-ThON was incorporated in the BTh copolymer backbone. Furthermore, the covalently immobilized L-ThON sequence showed selectivity in subsequent hybridization processes with a complementary target, demonstrating that L-ThONs can directly be used for manufacturing materials via an electropolymerization strategy. These results indicate that L-ThONs are promising candidates for the development of stable ON-based bioelectrochemical platforms.Fil: Kassahun, Getnet S.. Universite de Bordeaux; FranciaFil: Farias, Eliana Desiree. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Benizri, Sebastien. Universite de Bordeaux; FranciaFil: Mortier, Claudio. Universite de Bordeaux; FranciaFil: Gaubert, Alexandra. Universite de Bordeaux; FranciaFil: Salinas, Gerardo. Universite de Bordeaux; FranciaFil: Garrigue, Patrick. Cnrs, Bordeaux Inp, Ism Umr 5255, Site Enscbp, Pessac; FranciaFil: Kuhn, Alexander. Universite de Bordeaux; FranciaFil: Zigah, Dodzi. Université de Poitiers; Francia. Universite de Bordeaux; FranciaFil: Barthélémy, Philippe. Universite de Bordeaux; Franci

Additional file 1: of Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery

DLS data, zeta potentials, phase contrast microscopy, and TEM of SLNs synthetized in different experimental conditions, UHPLC dosages. (PDF 14710 kb

Predicting early death in older adults with cancer

International audienceBACKGROUND: Predicting early death after a comprehensive geriatric assessment (CGA) is very difficult in clinical practice. The aim of this study was to develop a scoring system to estimate risk of death at 100 days in elderly cancer patients to assist the therapeutic decision. METHODS: This was a multicentric, prospective cohort study approved by an ethics committee. Elderly cancer patients aged older than 70 years were enrolled before the final therapeutic decision. A standardised CGA was made before the treatment decision at baseline. Within 100 days, event~(death), oncologic and geriatric data were collected. Multivariate logistic regression was used to select the risk factors for the overall population. Score points were assigned to each risk factor using the β coefficient. Internal validation was performed by a bootstrap method. Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and accuracy with the mean c-statistic. FINDINGS: One thousand fifty patients (mean age: 82 years) joined the study from April 2012 to December 2014. The independent predictors were~metastatic cancers (odds ratio [OR] 2.5; 95% confidence interval [CI], [1.7-3.5] p\textless0 .001); gait speed\textless0.8~m/s (OR 2.1; 95% CI [1.3-3.3] p=0.001); Mini Nutritional Assessment (MNA)~\textless~17 (OR 8; 95% CI; [3.7-17.3] p\textless0.001), MNA <=23.5 and~>=~17 (OR 4.4; 95% CI, [2.1-9.1) p\textless0.001); performance status (PS)~\textgreater~2 (OR 1.7; 95% CI, [1.1-2.6)] p=0.015) and cancers other than breast cancer~(OR 4; 95% CI, [2.1-7.9] p\textless0.001). We attributed 4 points for MNA\textless17, 3 points for MNA between <=23.5 and~>=~17, 2 points for metastatic cancers, 1 point for gait speed \textless0.8~m/s, 1 point for PS~\textgreater~2 and 3 points for cancers other than breast cancer. The risk of death at 100 days was 4% for 0 to 6 points, 24% for 7 to 8 points, 39% for 9 to 10 points and 67% for 11 points. INTERPRETATION: To our knowledge, this is the first score which estimates early death in elderly cancer patients. The system could assist in the treatment decision for elderly cancer patients