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Supramolecularly Engineered Circular Bivalent Aptamer for Enhanced Functional Protein Delivery.

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Chemically engineered circular bivalent aptamers (cb-apt) were modified with β-cyclodextrin (βCD) for targeted intracellular delivery. This novel supramolecular system enhances serum stability and therapeutic cargo delivery, opening new applications for aptamer technology.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Chemical Biology

Background:

  • Circular bivalent aptamers (cb-apt) offer enhanced stability and molecular recognition compared to traditional aptamers.
  • Therapeutic applications of cb-apt are limited by the absence of functional modules for controlled interaction with therapeutic payloads.
  • A need exists for strategies to functionalize cb-apt for targeted delivery and diverse therapeutic applications.

Purpose of the Study:

  • To design and characterize a β-cyclodextrin-modified circular bivalent aptamer (cb-apt-βCD) for targeted intracellular delivery.
  • To investigate the supramolecular interactions between cb-apt-βCD and molecular therapeutics.
  • To evaluate the serum stability and intracellular delivery efficiency of the cb-apt-βCD system.

Main Methods:

  • Chemical conjugation of β-cyclodextrin (βCD) to circular bivalent aptamers (cb-apt).
  • Formation of supramolecular ensembles through host-guest chemistry between cb-apt-βCD and therapeutic molecules.
  • In vitro assessment of serum stability and intracellular delivery efficiency using model proteins and cytotoxic agents.

Main Results:

  • The cb-apt-βCD supramolecular ensemble demonstrated significantly improved serum stability compared to monomeric aptamers.
  • Enhanced intracellular delivery efficiency was observed, with up to 80% delivery of green fluorescent protein into targeted cells.
  • The system effectively delivered cytotoxic saporin to inhibit tumor cell growth, demonstrating therapeutic potential.

Conclusions:

  • Conjugating βCD to cb-apt creates a versatile platform for supramolecular assembly and targeted intracellular delivery.
  • This strategy overcomes limitations in functionalizing aptamers for therapeutic applications.
  • The cb-apt-βCD system offers a generalizable approach to expand aptamer functionality for novel biological and therapeutic uses.