Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil–Gold Nanoparticle Complexes
| Autor: | Amandine Pinto, Amanda K. A. Silva, Florent Carn, Florence Gazeau, Alba Nicolas-Boluda, Marc Pocard, Vladimir Mulens-Arias, Alice Balfourier |
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| Přispěvatelé: | Laboratoire MSC Matière et Systèmes Complexes, Université de Paris, CNRS UMR 7057, 75006 Paris, France. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hyperthermia
medicine.medical_treatment [SDV]Life Sciences [q-bio] General Physics and Astronomy Metal Nanoparticles 02 engineering and technology 010402 general chemistry 01 natural sciences Peritoneal cavity Mice Immune system Antineoplastic Combined Chemotherapy Protocols medicine Tumor Microenvironment Animals General Materials Science Peritoneal Neoplasms ComputingMilieux_MISCELLANEOUS Chemotherapy business.industry General Engineering Hyperthermia Induced Photothermal therapy 021001 nanoscience & nanotechnology medicine.disease Combined Modality Therapy 3. Good health 0104 chemical sciences medicine.anatomical_structure Fluorouracil Toxicity Colonic Neoplasms Cancer research Hyperthermic intraperitoneal chemotherapy Gold 0210 nano-technology business medicine.drug |
| Zdroj: | ACS Nano ACS Nano, American Chemical Society, 2021, 15 (2), pp.3330-3348. ⟨10.1021/acsnano.0c10276⟩ |
| ISSN: | 1936-0851 |
| Popis: | Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP-5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP-5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP-drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice. |
| Databáze: | OpenAIRE |
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