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Creusat G.,CNRS Laboratory of Design and Application of Bioactive Molecules | Rinaldi A.-S.,ESBS FRE 3211 | Weiss E.,ESBS FRE 3211 | Elbaghdadi R.,CNRS Laboratory of Design and Application of Bioactive Molecules | And 3 more authors.
Bioconjugate Chemistry

Small interfering RNAs offer novel opportunities to inhibit gene expression in a highly selective and efficient manner but depend on cytosolic translocation with synthetic delivery systems. The polyethylenimine (PEI) is widely used for plasmid DNA transfection. However, the water-soluble PEI does not form siRNA polyplexes stable enough in extracellular media for effective delivery. We previously showed that rendering PEI insoluble in physiological media, without modifying drastically its overall cationic charge density, by simple conjugation with natural hydrophobic α-amino acids, can lead to effective siRNA delivery in mammalian cells. In here, we comprehensively investigated the mechanism behind the excellent efficacy of the leading PEIY vector. Our data revealed that the underlining proton sponge property is key to the effectiveness of the tyrosine-polyethylenimine conjugate as it may allow both endosomal rupture and siRNA liberation via an optimal pH-sensitive dissolution of the PEIY self-aggregates. Altogether, these results should facilitate the development of novel and more sophisticated siRNA delivery systems. © 2010 American Chemical Society. Source

Sahu A.,Tata Memorial Center Kharghar | Nandakumar N.,Tata Memorial Center Kharghar | Sawant S.,Tata Memorial Center Kharghar | Krishna C.M.,Tata Memorial Center Kharghar

High mortality rates associated with oral cancers can be primarily attributed to the failure of current histological procedures in predicting recurrence. Identifying recurrence related factors can lead to improved prognosis, optimized treatment and enhanced overall outcomes. Serum Raman spectroscopy has previously shown potential in the diagnosis of cancers, such as head and neck, cervix, breast, oral cancers, and also in predicting treatment response. In the present study, serum was collected from 22 oral cancer subjects [with recurrence (n = 10) and no-recurrence (n = 12)] before and after surgery and spectra were acquired using a Raman microprobe coupled with a 40x objective. Spectral acquisition parameters were as follows: λex = 785 nm, laser power = 30 mW, integration time: 12 s and averages: 3. Data was analyzed in a patient-wise approach using unsupervised PCA and supervised PC-LDA, followed by LOOCV. PCA and PC-LDA findings suggest that recurrent and non-recurrent cases cannot be classified in before surgery serum samples; an average classification efficiency of ∼78% was obtained in after-surgery samples. Mean and difference spectra and PCA loadings indicate that DNA and protein markers may be potential spectral markers for recurrence. RS of post surgery serum samples may have the potential to predict the probability of recurrence in clinics, after prospective large-scale validation. © The Royal Society of Chemistry 2015. Source

Kumar P.,Tata Memorial Center Kharghar | Bhattacharjee T.,Tata Memorial Center Kharghar | Pandey M.,Tata Memorial Center Kharghar | Hole A.,Tata Memorial Center Kharghar | And 2 more authors.
Journal of Raman Spectroscopy

Oral cancer is a major cause of mortality in South Asian men owing to rampant tobacco abuse. Cancers are also reported in non-tobacco habitués, especially women, attributed to chronic irritations from irregular/sharp teeth, improper fillings, and poorly fit dentures. Conventional screening approaches are shown to be effective for high-risk groups (tobacco/alcohol habitués). Raman spectroscopy (RS) is being extensively explored as an alternate/adjunct tool for diagnosis and management of oral cancers. In a previous Raman study on sequential oral carcinogenesis using hamster buccal pouch model, misclassifications between spectra from control and carcinogen [7,12-dimethylbenz(a)anthracene (DMBA)]-treated tissues were observed. Histopathology of some control tissues suggested pathological changes, attributable to repeated forceps-induced irritations/trauma during animal handling. To explore these changes, in the present study, we recorded spectra from three different types of controls - vehicle control (n=45), vehicle contralateral (n=45), and DMBA contralateral (n=70) - exposed to varying degree of forceps handling, along with DMBA-treated pouches (n=70) using a 14-week carcinogenesis protocol. Spectra certified on the basis of histopathology and abnormal cell proliferation (cyclin D1 expression) were used to build models that were evaluated by independent test spectra from an exclusive set of DMBA-treated and control animals. Many DMBA-contralateral, vehicle-control, and vehicle-contralateral spectra were identified as higher pathologies, which subsequently corroborated with histopathology/cyclin D1 expression. Repeated forceps-mediated injuries/irritations, during painting and animal handling, may elicit inflammatory responses, leading to neoplasm. The findings of the study suggest that RS could identify micro-changes. Further, RS-based in vivo imaging can serve as a promising label-free tool for screening even in the non-habitué population where conventional screening is shown to be not effective. © 2016 John Wiley & Sons, Ltd. Source

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