Nanobody-Conjugated Theranostic Prodrug Targeting α_vβ₃ Integrin Enables Precision Cancer Therapy With Real-Time...

Area of Science:

• Oncology
• Nanotechnology
• Bioconjugate Chemistry

Background:

• Precision oncology demands integrated diagnostic and therapeutic strategies.
• Theranostic prodrugs offer targeted delivery and real-time monitoring.
• Alpha-v-beta-3 (αvβ3) integrin is a key target in various cancers.

Purpose of the Study:

• To design, synthesize, and evaluate a nanobody-based αvβ3 integrin-targeted theranostic prodrug (NBD).
• To assess NBD's efficacy in selective drug release, imaging, and tumor suppression.
• To compare NBD with a cRGD peptide-conjugated counterpart (cRBD).

Main Methods:

• Rational design and synthesis of the NBD system.
• Incorporation of a glutathione-responsive disulfide linker and an aza-BODIPY near-infrared fluorophore.
• Preclinical evaluation in αvβ3-overexpressing cancer cell lines and SKOV3 xenograft models.

Main Results:

• NBD exhibited superior tumor selectivity, intracellular activation, and cytotoxicity compared to cRBD.
• In vivo studies showed prolonged tumor retention, enhanced drug accumulation, and potent tumor suppression.
• Real-time imaging facilitated precise monitoring of NBD activation and distribution with minimal systemic toxicity.

Conclusions:

• Nanobody-guided theranostic platforms offer advantages for targeted drug delivery and image-guided cancer therapy.
• NBD demonstrates significant potential for reducing off-target effects in cancer treatment.
• The modular design of NBD provides a versatile framework for personalized cancer treatment strategies.