Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery...

Area of Science:

• Materials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Post-synthetic modification of covalent organic frameworks (COFs) is crucial for adding functionality.
• Introducing functional groups during 2D COF synthesis can compromise framework integrity due to interference with π-π stacking.
• Covalent organic frameworks offer potential for advanced material applications.

Purpose of the Study:

• To develop a stable drug delivery system by covalently conjugating an antitumor drug to a 2D COF.
• To investigate the impact of functional group incorporation on COF stability and drug release properties.
• To explore the potential of COF-drug conjugates for enhanced cell internalization.

Main Methods:

• Sequential substitution of monomers during the synthesis of a 2D COF (COF-5) to incorporate nucleophilic groups (primary amines).
• Covalent bonding of the antitumor drug camptothecin (CPT) to the modified COF.
• Water adsorption isotherm modeling to assess the hydrophobic effect and framework stability.
• Stability testing under physiological conditions.
• Evaluation of cell internalization kinetics.

Main Results:

• Successful direct incorporation of nucleophilic groups onto the pore wall of COF-5 during synthesis.
• Formation of a stable hydrophobic drug delivery system through covalent conjugation of camptothecin.
• Evidence of enhanced stability against boronate ester hydrolysis due to the hydrophobic effect induced by the CPT ligand.
• Improved cell internalization kinetics attributed to the hydrophobic nature of the COF-drug conjugate promoting lipophilic cell membrane interactions.

Conclusions:

• Direct incorporation of functional groups during 2D COF synthesis is feasible via sequential monomer substitution.
• Covalently conjugated COFs can form stable, hydrophobic drug delivery systems.
• The developed COF-drug conjugate demonstrates enhanced stability and improved cell internalization, paving the way for novel therapeutic applications.