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Engineering Radiocatalytic Nanoliposomes with Hydrophobic Gold Nanoclusters for Radiotherapy Enhancement.

Nazareth Milagros Carigga Gutierrez1, Tristan Le Clainche1, Anne-Laure Bulin1

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Gold nanocluster-loaded liposomes enhance X-ray therapy for pancreatic cancer by increasing radiation-induced hydroxyl radical production. This nanoliposome formulation shows promise for improving chemoradiation efficacy and safety in cancer treatment.

Keywords:
3D culture modelschemoradiotherapylipid nanotechnologymonochromatic synchrotron radiationoxaliplatinpancreatic cancerradiation therapyradiotherapy‐controlled drug deliverytumor permeability

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Chemoradiation therapy is a key treatment for pancreatic cancer, with ongoing research focused on enhancing its safety and effectiveness.
  • Liposomes are utilized to improve chemotherapy safety and deliver nanomaterials to tumors.
  • High-Z element-based radiocatalytic nanomaterials offer potential for targeted cancer therapy.

Purpose of the Study:

  • To investigate the interaction between X-rays and gold nanocluster-loaded nanoliposomes for pancreatic cancer treatment.
  • To evaluate the efficacy of these nanoliposomes in augmenting oxaliplatin chemoradiotherapy.
  • To assess the potential of nanoliposomes as carriers for radiocatalytic nanomaterials.

Main Methods:

  • Incorporation of hydrophobic gold nanoclusters (AuDDT) into nanoliposomal bilayers.
  • Assessment of X-ray induced hydroxyl radical (•OH) production by AuDDT-nanoliposomes.
  • Evaluation of cargo release from nanoliposomes upon X-ray irradiation.
  • Testing the efficacy of AuDDT-nanoliposomes in 3D pancreatic microtumor models and an orthotopic mouse model.

Main Results:

  • AuDDT-nanoliposomes significantly enhanced X-ray induced •OH production, particularly at energies above gold's K-shell binding energy.
  • X-ray irradiation induced dose- and formulation-dependent cargo release from AuDDT-nanoliposomes.
  • The radiocatalytic effect of AuDDT-nanoliposomes improved radiotherapy and oxaliplatin-chemoradiotherapy outcomes in pancreatic microtumors.
  • PEGylated AuDDT-nanoliposomes demonstrated high tumor accumulation in a mouse model.

Conclusions:

  • AuDDT-nanoliposomes effectively enhance chemoradiation dose using radiocatalytic nanomaterials.
  • Nanoliposomes show promise as carriers for high-Z elements in cancer therapy.
  • Further optimization of nanoliposomal loading of high-Z elements could advance chemoradiation strategies.