Engineered design of theranostic upconversion nanoparticles for tri-modal upconversion luminescence/magnetic resonance/X-ray computed tomography imaging and targeted delivery of combined anticancer drugs

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Abstract
Upconversion nanoparticles (UCNPs) are ideal building blocks for fabricating multifunctional theranostic agents for simultaneous diagnosis and therapy. We develop multifunctional nanoparticles based on NaGdF4:Yb/Er@NaGdF4 core–shell UCNPs, which are not only endowed with upconversion luminescence (UCL), magnetic resonance (MR) and X-ray computed tomography (CT) imaging ability, but also could be applied as nanocarriers for targeted drug delivery. We systematically investigate their upconversion luminescent, magnetic and X-ray attenuation properties. Importantly, for the first time, we report the controlled loading and delivery of a mixture of chemotherapeutic anticancer drugs, camptothecin (CPT) and doxorubicin (DOX), through UCNPs-based nanocarriers considering that the combined use of two or more drugs usually exhibits much better therapeutic efficacy than that of a single drug. By conjugating nanoparticles with folic acid (FA), which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted tri-modal UCL/MR/CT cell imaging and drug delivery with UCNPs. Our results suggest the as-prepared nanocomposites are highly versatile and could potentially be used for simultaneous imaging and therapeutic applications.

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