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New anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infection

Publication . Maciel, Dina; Guerrero-Beltrán, Carlos; Ceña-Diez, Rafael; Tomás, Helena; Muñoz-Fernández, M. Ángeles; Rodrigues, João

Acquired immune deficiency syndrome (AIDS) due to human immunodeficiency virus type-1 (HIV-1) represents one of the most important sexually transmitted infections (STI) worldwide. Great international efforts have been made to stop new infections but, to date, several compounds failed as microbicides at different stages of clinical trials. The quest to design new molecules that could prevent these infections is essential. In this work, we synthesized the first, second and third generations of anionic dendrimers having carboxylate and sulfonate terminal groups, respectively named G1C, G2C, G3C and G1S, G2S, and G3S, starting from a family of poly(alkylideneamine) dendrimers with nitrile termini. The anionic terminal groups of these dendrimers were expected to prompt them to act against HIV-1 infection. All dendrimers were fully characterized by 1H- and 13C-NMR, FTIR, MS and zeta potential techniques. Importantly, they were able to remain stable in the solid state and aqueous solutions at least for one and a half years. Screening of these six new dendrimers was then performed to shed light on their potential anti-HIV-1 activity and their mechanism of action. Results showed that the dendrimers were cytocompatible and that G1C and G1S dendrimers had important activity against R5-HIV-1NLAD8 and X4-HIV-1NL4.3 isolates by acting directly on viral particles and blocking their entry in host cells. Additionally, G1C and G1S dendrimers maintained their inhibitory effect at different pH values. Through a vaginal irritation assay carried out in BALB/c mice, the safety of these new dendrimers for topical application was also shown. Taken together, our results clearly show that G1C and G1S dendrimers are strong candidates for developing an effective microbicide to prevent HIV-1 new infections.

2019-05-16Journal article

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Metallodendrimers as HIV antiviral and anticancer agents

Publication . Maciel, Dina Maria Sousa; Rodrigues, João Manuel Cunha; Muñoz-Fernándes, Maria Ángeles

2020-12-16Doctoral thesis

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Piezoelectric electrospun nanomaterials as a plataform for biological applications

Publication . Wei, Huang; Pires, Pedro Filipe Duarte Louzeiro

Piezoelectric materials as new smart biomaterials show great potential for biological applications. Specifically, piezoelectric polyvinylidene fluoride (PVDF) electrospun nanofibers, possess outstanding properties, which provide many advantages in various healthcare applications. We followed a systematic fabrication approach to create a new device for mechanical stimulation of cells, based upon the inverse piezoelectric effect from functionalized PVDF nanofibers, and tested it with different cell lines. The major contents in this thesis are presented as follows: (1) Fibers fabrication and characterization Multi-walled carbon nanotubes (MWCNTs) were blended with PVDF to fabricate highly aligned PVDF/MWCNTs piezoelectric nanofibers. In this part we investigated the PVDF/MWCNTs nanofibers’ properties, such as, morphology, alignment, crystal structure, mechanical properties, piezoelectric output voltage and cytotoxicity. (2) Biological applications of inverse piezoelectric stimulation To explore the effect of mechanical stimulation on cellular behavior, specifically, morphology, proliferation, migration and differentiation, we selected three cell line models: NIH3T3 cells as fibroblasts; PC12 cells as neuroblastic cells; mesenchymal stem cells. All cells were submitted to an inverse piezoelectric stimulation over 30 minutes per day, with 10 V amplitude at 5 Hz frequency driving signal. It was found that inverse piezoelectric stimulation with PVDF/MWCNTs nanofibers, not just improved the proliferation of NIH3T3 cells, but also efficiently guided the cells migration. In the part of neuroblastic cells investigation, the adhesion, proliferation and differentiation results of PC12 cells submitted to the inverse piezoelectric stimulation shown a great improvement. In the study of mesenchymal stem cells (MSCs), the inverse piezoelectric PVDF/MWCNTs nanofibers could not improve the adhesion and proliferation of MSCs in early stage, but it improved the osteogenic differentiation. Therefore, according to our results, we believe that inverse piezoelectric stimulation with aligned PVDF/MWCNTs nanofibers holds a great potential on wound healing, nerves regeneration and bone tissue engineering applications.

2021-03-24Doctoral thesis

Open access

DNA/Dendrimer-based films: a novel material with potential biomedical applications

Publication . Castro, Rita Maria de; Tomás, Helena Maria Pires Gaspar; Pêgo, Ana Paula Gomes Moreira

Nesta tese de doutoramento, foram desenvolvidos novos materiais híbridos, sob a forma de filmes finos, essencialmente baseados em interações eletrostáticas estabelecidas entre moléculas de ácido desoxirribonucleico (ADN) e dendrímeros de poli(amidoamina) (PAMAM). Os dendrímeros PAMAM são moléculas à escala nanométrica que apresentam multi-valência e um baixo índice de polidispersão. Esta classe de moléculas tem sido muito estudada para a entrega de genes e fármacos em células, para além de muitas outras aplicações na área biomédica. Isto apenas é possível devido às suas propriedades físicas, químicas e estruturais, que permitem a interação eletrostática com ácidos nucleicos e conjugação à superfície e/ou encapsulamento de fármacos no seu interior. Neste trabalho, foi tirado proveito da capacidade destas moléculas interagirem com o ADN para obter novos materiais com aplicações biomédicas promissoras.

2018-07-23Doctoral thesis

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