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Integrin α2β1-Targeted Self-Assembled Nanocarriers for Tumor Bioimaging.

Arnon Fluksman1, Eliana Steinberg1, Natalie Orehov1

  • 1Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91121, Israel.

ACS Applied Bio Materials
|January 13, 2022
PubMed
Summary
This summary is machine-generated.

New nanocarriers targeting α2β1 integrins show promise for near-infrared (NIR) tumor imaging and image-guided surgery. OF27 nanocarriers effectively target tumors with high fluorescence and no organ toxicity.

Keywords:
3D spheroidA431 tumorNIRcyclic RTS peptidenanocarrierstargeted bioimagingα2β1 integrin

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Near-infrared (NIR) dyes are crucial for tumor imaging but have limitations.
  • A need exists for targeted nanocarriers to improve NIR dye delivery for diagnosis and image-guided surgery.
  • While Arg-Gly-Asp (RGD) peptides target αVβ3 integrins, Lys-Thr-Ser (KTS) peptides targeting collagen receptors α1β1/α2β1 integrins, overexpressed in tumors, remain underexplored for bioimaging.

Purpose of the Study:

  • To develop and evaluate a novel α2β1-integrin-targeted nanocarrier encapsulating an indocyanine green NIR dye for tumor bioimaging.
  • To assess the targeting specificity, safety, and in vivo efficacy of the developed nanocarriers.

Main Methods:

  • Synthesis of cyclic Lys(Arg)-Thr-Ser (KTS) peptides and a linear control peptide.
  • Preparation of integrin-targeted nanocarriers (ITNCs) OF5, OF27, and a non-targeted control OF70.
  • In vitro evaluation of selective binding to α2β1 integrin-expressing cells and tumor spheroids, cytotoxicity assays.
  • In vivo near-infrared (NIR) bioimaging in A431 tumor-bearing nude mice to assess biodistribution and tumor accumulation.

Main Results:

  • The ITNCs demonstrated selective association with α2β1 integrin-expressing cells and tumor spheroids.
  • In vitro cytotoxicity experiments confirmed the safety of the ITNCs.
  • In vivo NIR bioimaging revealed that ITNC OF27 exhibited higher fluorescent signals in tissues, enhanced tumor accumulation, and no cytotoxic effects on major organs.

Conclusions:

  • The developed α2β1-integrin-targeted nanocarrier, OF27, shows significant potential for in vivo tumor targeting and visualization in the NIR region.
  • OF27 represents an innovative pharmaceutical bioimaging system for improved tumor diagnosis and image-guided surgery.