posted on 2020-12-11, 19:41authored byVeronika Kozlovskaya, Aaron Alford, Maksim Dolmat, Maxwell Ducharme, Racquel Caviedes, Lauren Radford, Suzanne E. Lapi, Eugenia Kharlampieva
Radionuclide-functionalized
drug delivery vehicles capable of being
imaged via positron emission tomography (PET) are
of increasing interest in the biomedical field as they can reveal
the in vivo behavior of encapsulated therapeutics
with high sensitivity. However, the majority of current PET-guided
theranostic agents suffer from poor retention of radiometal over time,
low drug loading capacities, and time-limited PET imaging capability.
To overcome these challenges, we have developed hollow microcapsules
with a thin (<100 nm) multilayer shell as advanced theranostic
delivery systems for multiday PET tracking in vivo. The 3 μm capsules were 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
chelate the 89Zr radionuclide, which has a half-life of
3.3 days. We have found using radiochromatography that (TA/PVPON-DFO)6 capsules retained on average 17% more 89Zr than
their (TA/PVPON)6 counterparts, which suggests that the
covalent attachment of the DFO to PVPON provides stable 89Zr chelation. In vivo PET imaging studies performed
in mice demonstrated that excellent stability and imaging contrast
were still present 7 days postinjection. Animal biodistribution analyses
showed that capsules primarily accumulated in the spleen, liver, and
lungs with negligible accumulation in the femur, with the latter confirming
the stable binding of the radiotracer to the capsule walls. The application
of therapeutic ultrasound (US) (60 s of 20 kHz US at 120 W cm–2) to Zr-functionalized capsules could release the
hydrophilic anticancer drug doxorubicin from the capsules in the therapeutic
amounts. Polymeric capsules with the capability of extended in vivo PET-based tracking and US-induced drug release provide
an advanced platform for development of precision-targeted therapeutic
carriers and could aid in the development of more effective drug delivery
systems.