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Showing papers by "Valentín Ceña published in 2020"


Journal ArticleDOI
TL;DR: This review covers the proposed pathways involved in the cellular uptake of different NPs and submicron particles types as well as the role that some of the physicochemical nanoparticle characteristics play in the uptake pathway preferentially used by the nanoparticles to gain access and deliver their cargo inside the cell.
Abstract: Nanoparticles (NPs) and submicron particles are increasingly used as carriers for delivering therapeutic compounds to cells. Their entry into the cell represents the initial step in this delivery process, being most of the nanoparticles taken up by endocytosis, although other mechanisms can contribute to the uptake. To increase the delivery efficiency of therapeutic compounds by NPs and submicron particles is very relevant to understand the mechanisms involved in the uptake process. This review covers the proposed pathways involved in the cellular uptake of different NPs and submicron particles types as well as the role that some of the physicochemical nanoparticle characteristics play in the uptake pathway preferentially used by the nanoparticles to gain access and deliver their cargo inside the cell.

195 citations


Journal ArticleDOI
TL;DR: The different criteria and parameters to be addressed to prepare and develop druggable nanoparticles in general and dendrimers in particular are presented and discussed and the clinical translation of new nanomedicine issues are raised.

35 citations


Journal ArticleDOI
TL;DR: This review provides an analysis of the use of dendrimers modified with aptamers as nonviral vectors to specifically target tumor cells.

34 citations


Journal ArticleDOI
TL;DR: The conjugation of protein and peptides can improve tumor homing of nanoparticles, increase cellular penetration and attack specific drivers and vulnerabilities of the breast cancer cell to promote tumor cytotoxicity while reducing secondary effects in healthy tissues.
Abstract: The use of nanoparticles for breast cancer targeting and treatment has become a reality. They are safe and possess interesting peculiarities such as the unspecific accumulation into the tumor site ...

19 citations


Journal ArticleDOI
TL;DR: A more successful design of nanocarriers for efficient BBB crossing and delivery of diagnostic and/or therapeutic molecules to CNS will be needed to achieve efficient nanomedicine-based therapeutics for glioblastoma.
Abstract: Glioblastoma multiforme is the most common and the most aggressive primary brain tumor, with a median survival of 14 months. This dismal prognostic has turned research toward nanomedicine as a new ...

15 citations


Journal ArticleDOI
TL;DR: A robust delivery of the antigenic peptide to DCs is found and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction, but no expression of markers indicating activation of either B or T lymphocytes was observed.
Abstract: Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

10 citations


Journal ArticleDOI
TL;DR: The synthesis and characterization of star polymers consisting of functional trehalose-based macrocyclic cores and aminothiourea dendron arms are reported, which can be efficiently synthesized from sequential click reactions of orthogonal monomers, display no cytotoxicity, and efficiently complex and deliver plasmid DNA in vitro and in vivo.

9 citations


Journal ArticleDOI
TL;DR: It is found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo, suggesting that Macropincytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytotic.
Abstract: Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a β-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis.

7 citations