Intratumoral Biosynthesis of Gold Nanoclusters by Pancreatic Cancer to Overcome Delivery Barriers to Radiosensitization.
ACS Nano
; 18(3): 1865-1881, 2024 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-38206058
ABSTRACT
Nanoparticle delivery to solid tumors is a prime challenge in nanomedicine. Here, we approach this challenge through the lens of biogeochemistry, the field that studies the flow of chemical elements within ecosystems as manipulated by living cellular organisms and their environments. We leverage biogeochemistry concepts related to gold cycling against pancreatic cancer, considering mammalian organisms as drivers for gold nanoparticle biosynthesis. Sequestration of gold nanoparticles within tumors has been demonstrated as an effective strategy to enhance radiotherapy; however, the desmoplasia of pancreatic cancer impedes nanoparticle delivery. Our strategy overcomes this barrier by applying an atomic-scale agent, ionic gold, for intratumoral gold nanoparticle biosynthesis. Our comprehensive studies showed the cancer-specific synthesis of gold nanoparticles from externally delivered gold ions in vitro and in a murine pancreatic cancer model in vivo; a substantial colocalization of gold nanoparticles (GNPs) with cancer cell nuclei in vitro and in vivo; a strong radiosensitization effect by the intracellularly synthesized GNPs; a uniform distribution of in situ synthesized GNPs throughout the tumor volume; a nearly 40-day total suppression of tumor growth in animal models of pancreatic cancer treated with a combination of gold ions and radiation that was also associated with a significantly higher median survival versus radiation alone (235 vs 102 days, respectively).
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Nanopartículas Metálicas
Aspecto:
Implementation_research
Limite:
Animals
Idioma:
En
Revista:
ACS Nano
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos