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- Nanotechnology approaches for the delivery of antitumor drugs: the case of doxorubicinPublication . Gonçalves, Mara Isabel Jesus; Tomás, Helena Maria Pires Gaspar; Rodrigues, João Manuel Cunha; Lin, YulinOver the years, nanotechnology had a huge evolution and gathered the attention of many scientists, including those involved in medical sciences. Nanomedicine thus appeared, trying to overcome obstacles that still exist in conventional medicine, by providing innovative approaches for the diagnosis and treatment of diseases. Nowadays, cancer is considered one of the major causes of worldwide death. Doxorubicin (DOX) is a chemotherapeutic drug which is routinely used for cancer treatment. Due to its broad spectrum of activity, DOX is used as a first-line treatment combined with other drugs and procedures. However, this drug has several associated side effects, being the injury of the cardiac muscle tissue and myelosuppression the most reported. Cancer nanomedicine stands up as an alternative to conventional cancer therapy by using nanomaterials as drug carriers which, potentially, make the treatment more efficient and safe. Polymer-based nanomaterials are very promising vehicles for drug delivery, due to the easiness in modelling their properties. Over the years, polymers have proven to be capable of encapsulating and releasing drugs in a sustained manner, improving their biodistribution and accumulation in tumours. The main goal of this thesis was to find new drug delivery systems that could be able to encapsulate DOX and successfully deliver it inside cancer cells. Hopefully, using nanomaterials for DOX delivery, it will be possible to overcome the side effects which are frequently associated to this antitumor drug.
- Dendrimer-assisted formation of fluorescent nanogels for drug delivery and intracellular imagingPublication . Gonçalves, Mara; Maciel, Dina; Capelo, Débora; Xiao, Shili; Sun, Wenjie; Shi, Xiangyang; Rodrigues, João; Tomás, Helena; Li, YulinAlthough, in general, nanogels present a good biocompatibility and are able to mimic biological tissues, their unstability and uncontrollable release properties still limit their biomedical applications. In this study, a simple approach was used to develop dual-cross-linked dendrimer/alginate nanogels (AG/G5), using CaCl2 as cross-linker and amine-terminated generation 5 dendrimer (G5) as a cocrosslinker, through an emulsion method. Via their strong electrostatic interactions with anionic AG, together with cross-linker Ca(2+), G5 dendrimers can be used to mediate the formation of more compact structural nanogels with smaller size (433 ± 17 nm) than that (873 ± 116 nm) of the Ca(2+)-cross-linked AG nanogels in the absence of G5. Under physiological (pH 7.4) and acidic (pH 5.5) conditions, the sizes of Ca(2+)-cross-linked AG nanogels gradually decrease probably because of their degradation, while dual-cross-linked AG/G5 nanogels maintain a relatively more stable structure. Furthermore, the AG/G5 nanogels effectively encapsulate the anticancer drug doxorubicin (Dox) with a loading capacity 3 times higher than that of AG nanogels. The AG/G5 nanogels were able to release Dox in a sustained way, avoiding the burst release observed for AG nanogels. In vitro studies show that the AG/G5-Dox NGs were effectively taken up by CAL-72 cells (a human osteosarcoma cell line) and maintain the anticancer cytotoxicity levels of free Dox. Interestingly, G5 labeled with a fluorescent marker can be integrated into the nanogels and be used to track the nanogels inside cells by fluorescence microscopy. These findings demonstrate that AG/G5 nanogels may serve as a general platform for therapeutic delivery and/or cell imaging.
- Enhanced alpha-amylase inhibition activity of amine-terminated PAMAM dendrimer stabilized pure copper-doped magnesium oxide nanoparticlesPublication . Jeevanandam, Jaison; Gonçalves, Mara; Castro, Rita; Gallo, Juan; Bañobre-López, Manuel; Rodrigues, João; Gonçalves, Mara; Castro, Rita; Rodrigues, JoãoThe present work aims to prepare copper-doped MgO nanoparticles via a sol-gel approach and study their antidiabetic alpha-amylase inhibition activity with undoped MgO nanoparticles. The ability of G5 amine terminated polyamidoamine (PAMAM) dendrimer for the controlled release of copper-doped MgO nano particles to exhibit alpha-amylase inhibition activity was also evaluated. The synthesis of MgO nanoparticles via sol-gel approach and optimization of calcination temperature and time has led to the formation of nanoparticles with different shapes (spherical, hexagonal, and rod-shaped) and a polydispersity in size ranging from 10 to 100 nm with periclase crystalline phase. The presence of copper ions in the MgO nanoparticles has altered their crystallite size, eventually modifying their size, morphology, and surface charge. The efficiency of dendrimer to stabilize spherical copper-doped MgO nanoparticles (ca. 30 %) is higher than in other samples, which was confirmed by UV–Visible, DLS, FTIR, and TEM analysis. The amylase inhibition assay emphasized that the dendrimer nanoparticles stabilization has led to the prolonged enzyme inhibition ability of MgO and copper doped MgO nanoparticles for up to 24 h.