Persistent luminescence lanthanide systems for deep-penetration and long-lasting prostate cancer photodynamic therapy

  • WONG, Ka-Leung (PI)

Project: Research project

Project Details

Description

Photodynamic Therapy (PDT) emerging as a novel, efficacious cancer treatment modality with less side effects by locally converting “light” into reactive oxygen species, such as singlet oxygen (1O2) in vivo with photosensitizers to inhibit cancer growth is still failing to obtain its deserved popularity due to unsolved practical constraints: (i) photostability, (ii) cancer selectivity, and (ii) deep-tissue excitation failure of the currently existing molecular PDT agents. A prerequisite of further successful preclinical PDT translation as a “less-painful” anticancer treatment alternative to address the society’s demands is a fundamental breakthrough of designing new PDT agents.

Recently, surface-functionalized upconversion nanomaterials (UCNMs) of remarkable photophysical properties (excitable by near-infrared light sources) and excellent biocompatibility (target recognition) have held tremendous promise as the sought-after blueprint of new PDT agents. However, the true efficiency of claimed good 1O2 generation in vivo of such UCNMs is still uncertain. With the renaissance of persistent luminescence nanomaterials (PLNMs) research, we hypothesize that one-stop X-ray induced and rechargeable (deep tissue-penetrating radiation) PLNMs (hour-based emission duration) surface-coated with photosensitizers (1O2 generation excited intrinsically by its own persistent luminescence) and target-specific peptides (cancer cell selectivity) can provide the ultimate ideal solution as next-generation PDT agents for deeper-tissue anticancer treatment.

Prostate cancer, a deeper-tissue cancer, is the most common non-cutaneous cancer developed in men and remains the leading cause of cancer death in male mortality. The current prostate cancer treatments always involve invasive protocols that risk inevitable but indelible prostate damage. Hence, in this project, based on our experience in anthanide spectroscopy and peptide chemical biology, we aim to launch an anti-prostate cancer PDT research program by proposing and developing a series of novel multifunctional X-ray-persistent luminescence-PDT bioprobes. This smart system is based on low-dosage X-ray excitable (ex/in vivo) emissive persistent luminescence lanthanide-doped nanoparticles (Sr2MgSi2O7:Eu2+) anchored with porphyrins (persistent luminescence-photosensitized hours-long 1O2 generation) and bio- conjugated with specific peptides to target ERG (an overexpressed prostate cancer receptor). Simultaneous real-time NIR monitoring is also available throughout the whole process.

To substantiate our proposal, we have performed several proof-of-concept experiments: (i) 5% 1O2 was detected from porphyrins conjugated with persistent luminescence nanoparticles after 1 Gy single dose of X-ray radiation and (ii) the selectivity of binding of ERG with the proposed nanomaterials was confirmed by electrophoretic mobility shift assay. This project will be a practically translational cornerstone example of persistent luminescence-guided target-selective PDT treatment for prostate cancer imaging and therapy research.
StatusFinished
Effective start/end date1/01/1931/12/21

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