Browsing by Author "Pinheiro, Teresa"
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- Antitumoral and antimicrobial activities of block copolymer micelles containing gold bisdithiolate complexesPublication . Sousa, Andreia; Santos, Joana F.; Silva, Francisco; Sousa, Sílvia A.; Leitão, Jorge H.; Matos, António P.; Pinheiro, Teresa; Silva, Rafaela A. L.; Belo, Dulce; Almeida, Manuel; Marques, Fernanda; Fernandes, CéliaGold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]− (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]− were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]−/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]−. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.
- Dose rate effects on the selective radiosensitization of prostate cells by GRPR-targeted gold nanoparticlesPublication . Marques, Ana; Belchior, Ana; Silva, Francisco; Marques, Fernanda; Campello, Maria Paula Cabral; Pinheiro, Teresa; Santos, Pedro; Santos, Luis; Matos, António P. A.; Paulo, AntónioFor a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy.
- Modification of ZnO nanoparticles with silanes enables their application as anticancer agentsPublication . Marques, Fernanda; Tǎbǎcarub, Aurel; Bușilǎc, Mariana; Pinheiro, Teresa; Matos, António P. A.
- The Mössbauer effect using 57Fe-ferrabisdicarbollide ([o-57FESAN]−) : a glance into the potential of a low-dose approach for glioblastoma radiotherapyPublication . Buades, Ana B.; Pereira, Laura C. J.; Vieira, Bruno J. C.; Cerdeira, Ana C.; Waerenborgh, João C.; Pinheiro, Teresa; Matos, António P. A.; Pinto, Catarina G.; Guerreiro, Joana F.; Mendes, Filipa; Valic, Srecko; Teixidor, Francesc; Viñas, Clara; Marques, FernandaAlthough a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. To overcome this situation, more effective and selective treatments are necessary using anti-tumour agents that act in two or more ways and offer greater therapeutic benefits over single-mechanism entities. In this study, we report on treating cancer with Na[3,3′-57Fe(1,2-C2B9H11)2], which offers the possibility of dual action (radiation–drug combinations) to improve the clinical benefits and reduce healthy tissue toxicity. An approach to evaluating the potential of [o-57FESAN]− to treat glioblastoma using the Mössbauer effect is presented. As the therapeutic outcomes rely on the amount and distribution of [o-57FESAN]− inside the cells, several studies, using magnetization, Mössbauer spectroscopy and nuclear microscopy techniques, were performed to ascertain the uptake of [o-57FESAN]− in U87 glioblastoma cells. [o-57FESAN]− was found to be within the cells; 29% of its uptake was in the nuclear fraction, which is a particularly desirable target, because the nucleus is the cell's control centre where DNA and the transcription machinery reside. Irradiation studies with 2D and 3D cellular models of U87 cells showed that the growth inhibition effect observed was more pronounced when [o-57FESAN]− was used in combination with the Mössbauer effect in low total dose regimens, suggesting that this procedure either alone or as adjuvant may be useful for glioblastoma treatment.