Modified siRNAs for the study of the PAZ domain

Chemical modifications aimed at stabilizing the interaction between the 3'-end of siRNAs and the PAZ domain of RISC have been tested for their effect on RNAi activity. Such modifications contribute positively to the stability of siRNAs in human serum

Editorial: Novel cancer treatments based on autophagy modulation

[No abstract available

Modified siRNAs for the study of the PAZ domain

Chemical modifications aimed at stabilizing the interaction between the 3′-end of siRNAs and the PAZ domain of RISC have been tested for their effect on RNAi activity. Such modifications contribute positively to the stability of siRNAs in human serum.Peer reviewe

Albumin-based nanoparticles for the delivery of doxorubicin in breast cancer

SIMPLE SUMMARY: Doxorubicin (Dox) is a chemotherapeutic agent usually employed for the treatment of breast cancer. However, its use is limited because of the toxicities associated, and hence a proper delivery vehicle is necessary. In this sense, albumin-based nanocarriers are in the limelight for the successful delivery of chemotherapeutics because of safety, biocompatibility, and specific cancer-targeting properties. Herein, we have developed a nanocarrier system based on albumin, which selectively affects the tumor cells, and hence can revolutionize breast cancer therapy. The developed nanoparticles could be further used for the delivery of other hydrophobic drugs like SN38, which broadens the use of this system in the treatment of breast cancer. ABSTRACT: Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. The most widely used method for the preparation of albumin nanoparticles is by desolvation process using glutaraldehyde (GLU) as a cross-linker. However, limitations of GLU like toxicity and interaction with drugs force the need for alternative cross-linkers. In the present study, several cross-linking systems were evaluated for the preparation of Bovine Serum Albumin (BSA) nanoparticles (ABNs) encapsulating Doxorubicin (Dox). Based on the results obtained from morphological characterization, in vitro release, and therapeutic efficacy in cells, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)-modified ABNs (ABN-SPDP) was chosen. Since ABN-SPDP are formed with disulfide linkage, the drug release is facilitated under a highly reducing environment present in the tumor sites. The cytotoxicity studies of those ABN-SPDP were performed in three different breast cell lines, highlighting the mechanism of cell death. The Dox-encapsulated ABN-SPDP showed toxicity in both the breast cancer cells (MCF-7 and MDA-MB-231), but, remarkably, a negligible effect was observed in non-tumoral MCF-10A cells. In addition to the hydrophilic Dox, this system could be used as a carrier for hydrophobic drugs like SN38. The system could be employed for the preparation of nanoparticles based on human serum albumin (HSA), which further enhances the feasibility of this system for clinical use. Hence, the albumin nanoparticles developed herein present an excellent potential for delivering various drugs in cancer therapy

Synthesis of phosphoramidite monomers equipped with complementary bases for solid-phase DNA oligomerization

We describe the preparation of two monomers that bear complementary nucleobases at the edges (guanine-2′-deoxycytidine and 2- aminoadenine-2′-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their crosscoupling reactions into dinucleobase-containing monomers, and their oligomerization in the DNA synthesizerFunding from the European Research Council (ERC-Starting Grant 279548 PROGRAM-NANO) and MINECO (CTQ2014-57729-P, SAF2017-87305-R and CTQ2017- 84727-P) is gratefully acknowledge

Multifunctional albumin-stabilized gold nanoclusters for the reduction of cancer stem cells

Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release them when exposed to different internal stimuli (Glutathione and pH). This system has shown potent antitumor activity against breast and pancreatic cancer cells. Our studies indicate that the antineoplastic activity observed may be related to the reinforced DNA damage generated by the combination of the drugs. Moreover, this system presented antineoplastic activity against mammospheres, a culturing model for cancer stem cells, leading to an efficient reduction of the number of oncospheres and their size. In summary, the nanostructures reported here are promising carriers for combination therapy against cancer and particularly to cancer stem cells.This research was funded by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78454-C2-2-R, SAF2014-56763-R, and SAF2017-87305-R), Comunidad de Madrid (S2013/MIT-2850), Asociación Española Contra el Cáncer, and IMDEA Nanociencia IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686