Integrin α₂β₁-Targeted Self-Assembled Nanocarriers for Tumor Bioimaging

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.