doxorubicin using upconversion nanoparticles†

Lanthanide doped upconversion nanoparticles grafted with a photo-caged analog of doxorubicin allow near IR-release of doxorubicin. The low efficacy of current cancer chemotherapy is attributed to accumulation of drugs in non-cancerous tissues, eventually causing side effects. To address this serious issue, current research has focused on designing stimulus-responsive drug delivery agents.1 An array of delivery vehicles were designed involving components that are responsive to different stimuli including pH,2 intra-cellular enzymes,3 heat4 or light.5 Recently, we and other groups have reported photosensitive drug delivery systems, which are comprised of a nitrobenzyl-type ‘photocaged ’ anticancer drug conjugated to another small or macromolecule.6,7 In each of these cases drug release from the conjugate was mediated by UV light. A major limitation of this approach for eventual in vivo drug release is the low tissue penetrating ability of UV light and inevitable DNA damage.8–11 Unfortunately, the lower energy of more tissue-penetrating photons in the near IR region has precluded photochemical decaging at those wavelengths (although singlet oxygen dependent decaging has been achieved12,13). A potential solution to this problem is afforded by lanthanide doped upconverting nanoparticles (Ln-UCNPs). Ln-UCNPs have emerged as a novel class of luminescent probes with applications in many fields such as bio-imaging, diagnosis, drug delivery, and therapeutics due to the unique optical property of lanthanides known as upconversion.14,15 These nanoparticles, upon near IR excitation (typically 980 nm) can emit UV, visible and/or near infrared (NIR) light. In this work, we have focused on LiYF4:Tm 3+/ Yb3+-UCNPs because of their strong UV emission upon 980 nm excitation.16 Two strong emission bands centered at 353 and 368 nm, which are assigned to 3P0