Albumin is a highly attractive nanoplatform for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previous albumin-based nanoplatforms have had inconsistent blood circulation half-lives due to various modification methods. To address this, we developed a finely tuned click-chemistry-based albumin nanoplatform (CAN) with an extended circulation half-life and efficient tumor targeting ability.
Methods: The CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) using various molar ratios of ADIBO. The number of attached ADIBO moieties was determined via MALDI-TOF. Second, azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using the SPAAC reaction. Biodistribution and targeting efficiency of functionalized CANs were tested in mice.
Results: The degree of functionalization (DOF) was precisely controlled, optimizing the DOF for long circulation half-life (> 18 h). Functionalized CANs showed effective tumor targeting, with 64Cu-CAN-FA demonstrating specific folate receptor targeting in vivo and high uptake.
Conclusions: This optimized CAN nanoplatform offers a longer half-life and efficient tumor targeting, making it a promising albumin-based tumor theranostic agent.
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