4 research outputs found
Conjugados fotoativos para tratamento do cancro da bexiga
Mestrado em Bioquímica - Métodos BiomolecularesA terapia fotodinâmica (PDT) é uma metodologia emergente no tratamento de
diversas doenças oncológicas, tendo por base o uso de oxigénio, luz e um
fotossensibilizador (PS) para gerar reações citotóxicas no tecido tumoral.
Reconhecendo a potencialidade de PSs conjugados com diferentes
biomoléculas para serem reconhecidos especificamente por antigénios ou
recetores sobrexpressos nas células tumorais, este estudo pretendeu avaliar o
potencial fotodinâmico de PSs conjugados com moléculas de galactose (Gal),
com a albumina humana e bovina, e com o anticorpo monoclonal anti-CD104.
Numa primeira fase (Parte I) foram avaliadas as propriedades foto-químicas e -
físicas de uma porfirina (PorGal8) e de uma ftalocianina (PcGal16) conjugadas
com moléculas de galactose. Estes compostos mostraram-se solúveis em meio
aquoso, fluorescentes, foto-estáveis, geradores de espécies reativas de oxigénio
(ROS) após foto-ativação e apresentaram interação com a albumina humana.
Nas Partes II e III deste trabalho, foram realizados estudos in vitro de PDT com
as linhas celulares de cancro da bexiga HT-1376 e UM-UC-3, para avaliar o
potencial fotodinâmico da PorGal8 e PcGal16. Os conjugados demonstraram
toxicidade após foto-ativação, por um mecanismo dependente da formação de
ROS. Após PDT, a PorGal8 induziu alterações ao nível do citoesqueleto das
linhas celulares e apresentou-se mais eficaz com a linha celular UM-UC-3.
Posteriormente foi demonstrado que a resistência das células HT-1376 à PDT
com a PorGal8 é explicada pela baixa expressão de galectina-1 (proteína capaz
de reconhecer a PorGal8) e pela presença de células que sobrexpressão a
proteína ABCG2 (proteína capaz de bombear a PorGal8 para fora das células).
A PcGal16 apresentou também, inesperadamente, um modo de ação não
dependente da sua foto-ativação, sendo capaz de diminuir os níveis de
galectina-1 após o seu uptake pelas células. A síntese e o potencial biológico,
usando as células UM-UC-3, dos conjugados porfirina-albuminas e porfirinaanti-
CD104 são descritos na última parte deste trabalho (Parte IV). Estes
conjugados induziram reações citotóxicas após foto-ativação, sendo o
conjugado com o anticorpo mais eficaz que os conjugados com as albuminas.
Estes resultados obtidos com experiências in vitro demonstraram que os
conjugados exibem propriedades bio-físico-químicas promissoras e são
potenciais PSs para tratamento do cancro da bexiga.Photodynamic therapy (PDT) is a promising method, which has been studied
and applied to improve the treatment of several tumour types. PDT combines
molecular oxygen, light and a photosensitizer (PS) to generate cytotoxic
reactions in cancer cells. The potential of PSs conjugated with biomolecules
which will be recognized by antigens or receptors overexpressed in cancer
cells prompted us to validate the photodynamic activity of PSs conjugated
with galactose units, human and bovine serum albumins, and the monoclonal
antibody anti-CD104.
In Part I, the photo-chemical and -physical properties of a porphyrin
(PorGal8) and a phthalocyanine (PcGal16) conjugated with galactose
molecules were evaluated. The galacto-conjugates demonstrated to be water
soluble, fluorescents, photo-stable, generators of reactive oxygen species
(ROS) and able to interact with human serum albumin. The photodynamic
potential of PorGal8 and PcGal16 against human bladder cancer cell lines,
HT-1376 and UM-UC-3 is demonstrated in the parts II and III of this thesis.
The galacto-conjugates induced phototoxicity in both bladder cancer cell lines
by a ROS-mediated mechanism. After photo-activation, PorGal8 induces
changes in actin organization of bladder cancer cells and it was more photoactive
against UM-UC-3 cells. The resistance observed in HT-1376 cells after
PDT with PorGal8 was due to the low expression of galectin-1 (able to
recognize galactose molecules) and to the presence of cells overexpressing the
multi-drug resistant pump ABCG2. Unexpectedly, PcGal16 exhibited also a
“dark” mode of action by decreasing galectin-1 after its uptake in cancer cells.
In Part IV, the synthesis of a porphyrin conjugated with bovine and human
serum albumins and the monoclonal antibody anti-CD104 is reported, as well
as their biological potential against the human bladder cancer cell line UMUC-
3. These conjugates demonstrated high efficacy in destroying the cancer
cells, with the mAb anti-CD104 efficacy overruling the albumins one.
The in vitro results demonstrated that the conjugates exhibit excellent biophysic-
chemical properties and prompted us to envisage them as novel
anticancer drug candidates for bladder cancer treatment
Photodynamic Therapy
This book is dedicated to a topic related to the effects of photodynamic therapy organized by Biomedicines in 2022 (https://www.mdpi.com/topics/photodynamic_therapy). In medicine, the use of photodynamic therapy for the treatment of oncological and non-oncological diseases has been widely documented and well codified. In dermatology, the use varies from oncological to the treatment of chronic wounds, as well as in cosmetology for photo-rejuvenation. The 19 manuscripts published in this book cover all aspects of this therapy, including the discovery of new natural and synthetic photosensitizers, biomaterials and nanotechnology, in vitro and in vivo studies, and clinical trials
Nanocolloids for Nanomedicine and Drug Delivery
This Special Issue highlights novel nanocolloids like magnetic nanoparticles, nanomicelles, nanoliposomes, nanocapsules, and nanoclays, stimulating novel interests and ideas in research groups involved in the development of novel nanotools within the different areas of nanomaterials. The publication of original articles contributes to scientific progress in the area of personalized medicine and further stimulates the entering into clinical praxis of such new nanosystems