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

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.

Potential Application of Upconverting Nanoparticles for Brain Photobiomodulation.

Brain photobiomodulation (PBM) describes the use of visible to near-infrared light for modulation or stimulation of the central nervous system in both healthy individuals and diseased conditions. Although the transcranial approach to delivering light to the head is the most common technique to stimulate the brain, delivery of light to deeper structures in the brain is still a challenge. The science of nanoparticle engineering in combination with biophotonic excitation could provide a way to overcome this problem. Upconversion is an anti-Stokes process that is capable of transforming low energy photons that penetrate tissue well to higher energy photons with a greater biological effect, but poor tissue penetration. Wavelengths in the third optical window are optimal for light penetration into brain tissue, followed by windows II, IV, and I. The combination of trivalent lanthanide ions within a crystalline host provides a nanostructure that exhibits the upconversion phenomenon. Upconverting nanoparticles (UCNPs) have been successfully used in various medical fields. Their ability to cross the brain-blood barrier and their low toxicity make them a good candidate for application in brain disorders. It is possible that delivery of UCNPs to the brainstem or deeper parts of the cerebral tissue, followed by irradiation using light wavelengths with good tissue penetration properties, could allow more efficient PBM of the brain.