Carrier proteins-based boron delivery to tumor

Area of Science:

• Bioconjugation Chemistry
• Nanomedicine
• Boron Neutron Capture Therapy (BNCT)

Background:

• Transferrin (TF) is a serum protein crucial for iron transport.
• TF receptor-mediated endocytosis is a key cellular uptake mechanism.
• Boron-containing compounds are investigated for targeted therapies like BNCT.

Purpose of the Study:

• To conjugate maleimide-functionalized closo-dodecaborate (MID) to transferrin (TF).
• To investigate the cellular uptake and in vivo biodistribution of MID-TF conjugates.
• To evaluate the potential of MID-TF as a targeted delivery system for boron delivery.

Main Methods:

• Conjugation of maleimide-functionalized closo-dodecaborate to transferrin at room temperature.
• Cellular accumulation studies demonstrating time- and concentration-dependent uptake via TF receptor.
• In vivo biodistribution studies in colon 26-bearing mice comparing MID-TF and MID-bovine serum albumin (BSA).

Main Results:

• Successful conjugation of MID to TF without affecting TF's biological function.
• Time- and concentration-dependent cellular accumulation of MID-TF conjugates mediated by the TF receptor.
• Selective accumulation of MID-TF into tumors in mice, similar to MID-BSA, but with lower boron concentration, suggesting limited EPR effect due to smaller TF size.

Conclusions:

• MID-TF conjugates can be effectively synthesized and exhibit targeted cellular uptake.
• MID-TF demonstrates selective tumor accumulation in vivo, indicating potential for targeted boron delivery.
• The smaller molecular weight of TF compared to BSA may limit the enhanced permeability and retention (EPR) effect in passive tumor targeting.