Improved Cancer Targeting by Multimerizing Aptamers on Nanoscaffolds

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Aptamers are single-stranded oligonucleotides with high target affinity and specificity.
• Aptamers offer advantages over antibodies for in vitro production and applications in bioimaging and drug delivery.
• Multimerization of aptamers can enhance binding strength and specificity for in vivo applications.

Purpose of the Study:

• To present a robust and modular method for assembling multiple aptamers and functional agents into a single nanostructure.
• To demonstrate the utility of this method for creating multivalent aptamers with improved targeting capabilities.

Main Methods:

• A modular "click chemistry" approach was used to assemble up to three aptamers and a fluorophore.
• The method requires only a single reactive handle on each aptamer for conjugation.
• The assembly process was validated using cancer-targeting aptamers (A9g and GL21.T) and a prostate-specific membrane antigen (PSMA)-targeting aptamer.

Main Results:

• Multimerization of A9g and GL21.T aptamers significantly increased cancer cell uptake.
• Multivalent PSMA-targeting aptamers demonstrated enhanced tumor specificity in vivo.
• The method allows for stoichiometric attachment of multiple functionalities, including imaging and therapeutic agents.

Conclusions:

• The presented method provides a versatile platform for aptamer multimerization and the creation of multifunctional nanomedicines.
• This approach facilitates combinatorial screening and the design of advanced aptamer-based therapeutics and diagnostics.
• The developed nanostructures show promise for improving the efficacy of cancer targeting and drug delivery.