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.

2016Journal article

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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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