Radioisotope functionalized drug delivery vehicles capable of producing positron emission tomography (PET) imaging contrast have gained interest in the biomedical field due to the ability to track in vivo behavior of microcapsule therapeutics and the high sensitivity of detecting radionucleotide emissions for improved biodistribution quantification. However, the majority of current PET-guided theragnostic agents suffer from low loading capacities, poor retention of drug and stability over time, and time-limited PET imaging capability. To overcome these challenges, we have explored hollow microcapsules with a thin (&lt;100 nm) multilayer shell as advanced theranostic delivery systems. The 3-µm polymeric shells are fabricated via the aqueous multilayer assembly of a natural antioxidant, tannic acid (TA), and a poly(N-vinylpyrrolidone) (PVPON) copolymer containing monomer units functionalized with deferoxamine (DFO) to carry 89Zr radioisotope which has a half-life of 3.3 days. We explored the effects of PVPON-DFO composition and localization within the capsule shell on the stability of the radioisotope chelation. The capsule properties were characterized by SEM, AFM and radio chromatography. We also show that anticancer drug doxorubicin encapsulated into the TA/PVPON-DFO microcapsule interior cavities can be released from the microcapsules in response to therapeutic ultrasound. Time-dependent in vivo biodistribution of TA/PVPON-DFO-89Zr capsules were explored in healthy BALB/c mice and athymic nude mice for 7 days post-injection using PET imaging. These polymeric capsules with the capability for their extended in vivo PET-based tracking and ultrasound-induced drug release may provide an advanced platform for development of precision-targeted therapeutic carriers and could aid in the development of more effective drug delivery systems.

PET-guided drug delivery from ultrasound-sensitive multilayer microcapsules

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.