Publicação
Curcumin loaded lactobionic acid modified chitosan-nanoparticles for hepatic cancer therapy
| Resumo: | Worldwide, hepatocellular carcinoma (HCC) is responsible for most liver cancer diagnoses and deaths. Primary liver cancer is the seventh most occurring type of cancer, and it is the fourth most responsible for mortal cases. In recent years, nanotechnology has been used as a tool for fighting HCC, mainly its early diagnosis and treatment of advanced forms, which has improved therapeutic agents aiming future clinical practices. Curcumin is a polyphenol which has been shown to target multiple signaling molecules, and proved to have antiangiogenic, anti-inflammatory, antioxidant, and antitumor effects, which applies to HCC. However, it has some limitations. Due to its hydrophobic characteristics result in poor solubility and absorption, rapid metabolism and elimination, necessitating the development of a safe delivery platform. Chitosan (CS), derived from a natural polysaccharide, the chitin, has been utilized for preparing nanoparticles and loading into them small pharmacologically active molecules. Chitosan has favorable properties such as good biodegradability, low toxicity, and easy modifiability. More recently, it has been discovered that CS itself possesses anti-carcinogenic and hepato-protective properties. The modifiability of this polymer is particularly advantageous as it allows to link some molecules for better targeting to specific cells. Specifically, by expressing galactose, CS can effectively target the Asialoglycoprotein Receptor (ASGPR) present on hepatocytes of human carcinoma cell lines. The objective of this work was to develop, characterize and study curcumin encapsulated lactobionic acid modified chitosan nanoparticles (NPs), which present a galactose moiety on chitosan’s surface. These NPs were characterized for their cytotoxicity on hepatocellular carcinoma cells and healthy immune cells, registering overall no cytotoxicity at the tested concentrations. Additionally, their effect on oxidative stress was also verified, which confirmed curcumin’s antioxidant potential. Their immune response profile was also studied, with none of the nanoparticles stimulating pro-inflammatory cytokines. These contributions could provide significant insights for future studies using these NPs, as a part of potential cancer therapy and immunomodulation. |
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| Autores principais: | Remondes, Armando Manuel Machado |
| Assunto: | Curcumina Nanopartículas de quitosano Recetor de asialoglicoproteína Carcinoma hepatocelular Direcionado para o fígado Curcumin Chitosan nanoparticles Asialoglycoprotein receptor Hepatocellular Carcinoma Liver targeting |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Worldwide, hepatocellular carcinoma (HCC) is responsible for most liver cancer diagnoses and deaths. Primary liver cancer is the seventh most occurring type of cancer, and it is the fourth most responsible for mortal cases. In recent years, nanotechnology has been used as a tool for fighting HCC, mainly its early diagnosis and treatment of advanced forms, which has improved therapeutic agents aiming future clinical practices. Curcumin is a polyphenol which has been shown to target multiple signaling molecules, and proved to have antiangiogenic, anti-inflammatory, antioxidant, and antitumor effects, which applies to HCC. However, it has some limitations. Due to its hydrophobic characteristics result in poor solubility and absorption, rapid metabolism and elimination, necessitating the development of a safe delivery platform. Chitosan (CS), derived from a natural polysaccharide, the chitin, has been utilized for preparing nanoparticles and loading into them small pharmacologically active molecules. Chitosan has favorable properties such as good biodegradability, low toxicity, and easy modifiability. More recently, it has been discovered that CS itself possesses anti-carcinogenic and hepato-protective properties. The modifiability of this polymer is particularly advantageous as it allows to link some molecules for better targeting to specific cells. Specifically, by expressing galactose, CS can effectively target the Asialoglycoprotein Receptor (ASGPR) present on hepatocytes of human carcinoma cell lines. The objective of this work was to develop, characterize and study curcumin encapsulated lactobionic acid modified chitosan nanoparticles (NPs), which present a galactose moiety on chitosan’s surface. These NPs were characterized for their cytotoxicity on hepatocellular carcinoma cells and healthy immune cells, registering overall no cytotoxicity at the tested concentrations. Additionally, their effect on oxidative stress was also verified, which confirmed curcumin’s antioxidant potential. Their immune response profile was also studied, with none of the nanoparticles stimulating pro-inflammatory cytokines. These contributions could provide significant insights for future studies using these NPs, as a part of potential cancer therapy and immunomodulation. |
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