1 research outputs found
Photocontrolled Release of Doxorubicin Conjugated through a Thioacetal Photocage in Folate-Targeted Nanodelivery Systems
Despite
their proven ability for precise and targeted release,
nanoplatform systems for photocontrolled delivery often face formidable
synthetic challenges, in part due to the paucity of advanced linker
strategies. Here, we report on a novel linker strategy using a thioacetal <i>ortho</i>-nitrobenzaldehyde (TNB) cage, demonstrating its application
for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable
linker, TNBÂ(OH), which presents two identical arms, each terminated
with a hydroxyl functionality, was prepared in a single step from
6-nitroveratraldehyde. TNBÂ(OH) was used to cross-link Dox to a folate
receptor (FAR)-targeting polyÂ(amidoamine) dendrimer conjugate G5Â(FA)<sub><i>n</i>=5.4</sub>(Dox)<sub><i>m</i>=5.1</sub>, and also used to prepare an upconversion nanocrystal (UCN) conjugate,
UCN–PPIX@(Dox)Â(G5FA), a larger core/shell nanostructure. In
this core/shell nanostructure, the UCN core emits UV and visible light
luminescence upon near-infrared (NIR) excitation, allowing for the
photocleavage of the TNB linker as well as the photostimulation of
protoporphyrin IX (PPIX) coupled as a cytotoxic photosensitizer. Drug-release
experiments performed in aqueous solutions with long-wavelength ultraviolet
A (UVA) light showed that Dox release occurred rapidly from its TNB
linked form or from its dendrimer conjugated form with comparable
decay kinetics. Cellular toxicity studies in FAR-overexpressing KB
carcinoma cells demonstrated that each nanoconjugate lacked intrinsic
cytotoxicity until exposed to UVA or NIR (980 nm) (for the UCN nanoconjugate),
which resulted in induction of potent cytotoxicity. In summary, this
new TNB strategy offers synthetic convenience in drug conjugation
chemistry with the ability for the temporal control of drug activation
at the delivery site