PUBLICATION

Porphyrin-based bridged silsesquioxane nanoparticles for targeted two-photon photodynamic therapy of zebrafish xenografted with human tumor

Authors
Dib, S., Aggad, D., Mauriello Jimenez, C., Lakrafi, A., Hery, G., Nguyen, C., Durand, D., Morère, A., El Cheikh, K., Sol, V., Chaleix, V., Dominguez Gil, S., Bouchmella, K., Raehm, L., Durand, J.O., Boufatit, M., Cattoën, X., Wong Chi Man, M., Bettache, N., Gary-Bobo, M.
ID
ZDB-PUB-200729-9
Date
2019
Source
Cancer reports (Hoboken, N.J.)   2: e1186 (Journal)
Registered Authors
Keywords
bridged silsesquioxane nanoparticles, human tumor targeting, photodynamic therapy, two‐photon excitation
MeSH Terms
  • Animals
  • Breast Neoplasms/diagnosis
  • Breast Neoplasms/drug therapy*
  • Breast Neoplasms/pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Injections, Intravenous
  • Lasers
  • Microscopy, Fluorescence, Multiphoton
  • Nanoparticles/administration & dosage*
  • Nanoparticles/chemistry
  • Nanoparticles/radiation effects
  • Photochemotherapy/instrumentation
  • Photochemotherapy/methods*
  • Photosensitizing Agents/administration & dosage*
  • Photosensitizing Agents/chemistry
  • Porphyrins/administration & dosage
  • Porphyrins/chemistry
  • Silanes/administration & dosage
  • Silanes/chemistry
  • Theranostic Nanomedicine/instrumentation
  • Theranostic Nanomedicine/methods*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
32721109 Full text @ Cancer Rep (Hoboken)
Abstract
Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine.
In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small-sized nanoparticles were functionalized with PEG and mannose (PORBSNs-mannose) in order to target breast tumors in vivo.
The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two-photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs-mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two-photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation.
We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs-mannose injected in the blood stream of zebrafish xenografted with human tumors.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping