Multilayer Microcapsules with Shell-Chelated ⁸⁹Zr for PET Imaging and Controlled Delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Radiochemistry

Background:

• Positron emission tomography (PET) imaging offers high sensitivity for tracking drug delivery in vivo.
• Current PET-guided theranostic agents face challenges including poor radiometal retention, low drug loading, and limited imaging duration.
• Advanced delivery systems are needed to overcome these limitations for effective theranostics.

Purpose of the Study:

• To develop novel hollow microcapsules for enhanced, multiday in vivo PET tracking and targeted drug delivery.
• To improve radiometal retention and drug loading capacity compared to existing theranostic agents.
• To demonstrate ultrasound-triggered drug release from the developed microcapsule system.

Main Methods:

• Fabrication of 3 μm hollow microcapsules using aqueous multilayer assembly of tannic acid (TA) and poly(N-vinylpyrrolidone) (PVPON) functionalized with deferoxamine (DFO).
• Chelation of the 89Zr radionuclide to DFO-functionalized PVPON for PET imaging.
• In vivo PET imaging and biodistribution studies in mice, followed by ultrasound-induced doxorubicin release experiments.

Main Results:

• The (TA/PVPON-DFO)6 microcapsules demonstrated significantly improved 89Zr retention (17% higher) compared to controls, indicating stable chelation.
• In vivo PET imaging showed excellent stability and imaging contrast up to 7 days post-injection in mice.
• Therapeutic ultrasound successfully triggered the release of doxorubicin from the microcapsules in therapeutic amounts.

Conclusions:

• Developed multilayer microcapsules offer stable, long-term in vivo PET tracking capabilities.
• The system provides a platform for precision-targeted drug delivery with ultrasound-triggered release.
• These advanced theranostic carriers hold promise for developing more effective drug delivery systems.