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Projeto de investigação
CONTROLLED ENZYMATIC ASSEMBLY OF SSDNA-FUNCTIONALIZED DENDRIMERS FOR BIOMEDICAL APPLICATIONS
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Fine tuning of the pH-sensitivity of laponite–doxorubicin nanohybrids by polyelectrolyte multilayer coating
Publication . Xiao, Shili; Castro, Rita; Maciel, Dina; Gonçalves, Mara; Shi, Xiangyang; Rodrigues, João; Tomás, Helena
Despite the wide research done in the field, the development of advanced drug delivery systems with improved drug delivery properties and effective anticancer capability still remains a great challenge. Based on previous work that showed the potentialities of the nanoclay Laponite as a pH-sensitive doxorubicin (Dox) delivery vehicle, herein we report a simple method to modulate its extent of drug release at different pH values. This was achieved by alternate deposition of cationic poly(allylamine) hydrochloride and anionic poly(sodium styrene sulfonate) (PAH/PSS) polyelectrolytes over the surface of Dox-loaded Laponite nanoparticles using the electrostatic layer-by-layer (LbL) self-assembly approach. The successful formation of polyelectrolyte multilayer-coated Dox/Laponite systems was confirmed by Dynamic Light Scattering and zeta potential measurements. Systematic studies were performed to evaluate their drug release profiles and anticancer efficiency. Our results showed that the presence of the polyelectrolyte multilayers improved the sustained release properties of Laponite and allowed a fine tuning of the extension of drug release at neutral and acidic pH values. The cytotoxicity presented by polyelectrolyte multilayer-coated Dox/Laponite systems towards MCF-7 cells was in accordance with the drug delivery profiles. Furthermore, cellular uptake studies revealed that polyelectrolyte multilayer-coated Dox/Laponite nanoparticles can be effectively internalized by cells conducting to Dox accumulation in cell nucleus.
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.
Bioinspired hybrid DNA/dendrimer-based films with supramolecular chirality
Publication . Castro, Rita; Granja, Pedro L.; Rodrigues, João; Pêgo, Ana Paula; Tomás, Helena; Castro, Rita; Rodrigues, João; Pêgo, Ana Paula; Tomás, Helena
Bioinspired hybrid DNA/dendrimer films were obtained by heating long double-stranded DNA (dsDNA)
above its melting temperature and, while in the denatured state, mixing it with poly(amidoamine) (PAMAM)
dendrimers, followed by controlled cooling. The formation of these new types of films was found to be
dependent on several parameters, including the initial heating temperature, pH, buffer composition,
dendrimer generation, amine/phosphate (N/P) ratio, and cooling speed. In addition to the PAMAM
dendrimers (generations 3, 4, and 5), films could also be produced with branched poly(ethylenimine) with
a molecular weight of 25 kDa. The results indicated that these films were formed not only through
electrostatic interactions established between the negatively charged DNA molecules and the positive
dendrimers, as expected, but also through random rehybridization of the single-stranded DNA (ssDNA)
during the cooling process. The resulting films are water-insoluble, transparent when thin, highly elastic
when air-dried, exceptionally stable over extended periods, cytocompatible, and easily scalable. Notably,
the slow cooling process allowed for the establishment of at least a partially ordered structure in the films,
as revealed by circular dichroism, providing evidence of supramolecular chirality. It is envisioned that these
films may have significant potential in biomedical applications, such as drug/gene delivery systems,
platforms for cell-free DNA transcription and components in biosensors.
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Fundação para a Ciência e a Tecnologia
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Número da atribuição
SFRH/BD/87465/2012