Activatable Photodynamic Therapy with Therapeutic Effect Prediction Based on a Self-correction Upconversion Nanoprobe

Abstract

Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low “off-target” damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF4:Gd@NaYF4:Er,Yb@NaYF4:Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.

Most recent advances on enzyme‐activatable optical probes for bioimaging

“…Considering the critical roles of cathepsin B in tumor-associated processes, a series of cathepsin Bactivatable probes have been recently reported for bioimaging or theranostics. [120][121][122][123][124] The most recently reported probes 35 and 36 are depicted in Figure 17 to elucidate the design principle, working mechanism, and performance of cathepsin Bactivatable probes.…”

“…Reproduced with permission. [123] Copyright 2020, American Chemical Society risk, poor overall survival, high proliferative index, and the highest rate of metastasis, patients with triple negative breast cancer are presently the subgroup with the worst outcome, yielding a key need for developing novel efficient therapeutic treatments for triple negative breast cancer. [125] Moreover, diagnosing triple negative breast cancer in a precise manner is crucial for early therapeutic intervention.…”

Multipath optical thermometry realized in CaSc2O4: Yb3+/Er3+ with high sensitivity and superior resolution

“…Upconversion (UC) luminescence is referred to radiate ultraviolet or visible light through absorbing two or more near‐infrared photons with low energy 1‐4 . Benefiting from such a unique optical property, UC materials have attracted much attention for the application of drug delivery, biological imaging, photodynamic therapy, photothermal therapy, three‐dimensional display, etc 5‐9 . In the past few years, UC materials have also been found to own outstanding temperature sensing properties which can afford a contactless thermometry in many special industries, such as coal mining, metal smelting, petrochemicals, biomedicine, and so on 10,11 .…”

“…[1][2][3][4] Benefiting from such a unique optical property, UC materials have attracted much attention for the application of drug delivery, biological imaging, photodynamic therapy, photothermal therapy, three-dimensional display, etc. [5][6][7][8][9] In the past few years, UC materials have also been found to own outstanding temperature sensing properties which can afford a contactless thermometry in many special industries, such as coal mining, metal smelting, petrochemicals, biomedicine, and so on. 10,11 In particular, the fluorescence intensity ratio (FIR) between two thermally coupled energy levels of trivalent rare earth ions is considered to be a promising technology to provide fast and accurate optical thermometry, due to its rapid response capability, high spatial resolution, strong anti-jamming ability, etc.…”

Spiropyran-modified upconversion nanocomposite as a fluorescent sensor for diagnosis of histidinemia

“…The emission uorescence of different color can be obtained by doping different rare earth ions. These advantages make it have great development in applications such as bioimaging, 28,29 biosensing, 30,31 photothermal/photodynamic therapy 32,33 and multi-mode diagnosis. 34 In this work, we have developed a upconversion uorescent nanosensor for the diagnosis of histidinemia.…”