One and Two-Photon Activated Photoremovable Protecting Groups for Real-Time-Monitoring of Dual Drug Delivery

Our group has designed and synthesized various photoactivable protecting groups which can cage and release bioactive molecules. Further by tuning the substituents, we made it possible to control the wavelength and rate of release. We further utilized these photoremovable protecting groups for the controlled release of drugs and real time monitoring of the drug released. In this process, since the drug molecule is covalently attached with a photoactive molecule, it loses its activity temporarily, thereby ruling out the possibility of premature release or leaching of the drug. Once the system reaches the target site, the drug can be released from the photoactive molecule through photolysis, thus restoring its activity. Some of the newly developed protecting groups by our group are perylen-3-ylmethyl, 1-acetylpyrene, 1-hydroxyacetylpyrene, acridine-9-ylmethyl, acetyl carbazole. These newly developed protecting groups are highly fluorescent and can absorb in the visible region. We have been able to utilize these protecting groups in releasing single and dual anticancer drugs. We have recently developed p-hydroxyphenacyl-benzothiazole-chlorambucil conjugate as a real time monitoring drug delivery system assisted by excited state intramolecular proton transfer. Here, we have modified a well-known phototrigger, the p-hydroxyphenacyl (pHP) group by making it fluorescent and increasing its excitation wavelength above 400 nm so that it can be efficiently utilized as drug delivery agent in the area of theranostics.

Two-photon activated photoremovable protecting groups (PRPGs) have become a useful tool for the delivery of bioactive molecules. Because they provide advantages like (i) precise delivery of active molecules both spatially and temporally in a non-invasive way (ii) deeper penetration into biological samples and (iii) reduces the illumination duration, thus mitigating the harmful effects associated with the light on biological tissues. Our group has recently designed and synthesized various two-photon based protecting groups which can cage and release bioactive molecules, with substitutions like alcohols, acids, amines etc., at a specific site. We have further utilized these photoremovable protecting groups for the controlled release of drugs and real time monitoring of the drug release. Some of the newly developed two-photon activated protecting groups by our group are carbazole fused o-hydroxycinnamate and ESIPT based p-hydroxy phenacyl. These newly developed two-photon activated protecting groups are highly fluorescent and able to release dual anticancer drugs with real-time monitoring ability in the NIR region.