Natural Product-Based Upconversion-Downshifting Photosensitizers in Photodynamic Therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Photochemistry

Background:

• Natural product photosensitizers (PSs), including coumarin, riboflavin, curcumin, chlorophyll derivatives, and hypocrellin, offer superior safety profiles compared to synthetic PSs.
• Lanthanide ions (Yb3+, Er3+, Nd3+, Gd3+, Tm3+) possess unique photophysical properties like sharp 4f-4f transitions and long-lived excited states, enabling upconversion and downshifting luminescence.
• Upconversion nanoparticles (UCNPs) and upconversion-downshifting nanoparticles (UDNPs) are emerging platforms for generating reactive oxygen species (ROS) in photodynamic therapy (PDT).

Purpose of the Study:

• To review and synthesize recent advances in natural product-based upconversion photosensitizers for photodynamic therapy.
• To integrate insights into lanthanide photophysics, natural product PSs, and nanoplatform design.
• To evaluate the potential of UCNPs and UDNPs in enhancing PDT efficacy.

Main Methods:

• A comprehensive literature review was conducted across multiple electronic databases (WanFang Data, PubMed, ScienceDirect, Scopus, Web of Science, Springer Link, SciFinder, CNKI) from 1995 to 2026.
• The search focused on photodynamic therapy, lanthanide photophysics, natural product photosensitizers, and nanoplatforms (UCNPs, UDNPs).
• Relevant publications were identified and synthesized to establish a conceptual framework.

Main Results:

• Natural product-based upconversion PSs exhibit advantages such as low dark toxicity, biocompatibility, and multimodal actions.
• Lanthanide-enhanced systems address limitations of traditional PDT, including shallow tissue penetration, photobleaching, and low singlet oxygen quantum yields.
• Recent advances in UCNPs and UDNPs demonstrate their potential for effective ROS generation in PDT.

Conclusions:

• Natural product-based upconversion PSs represent an innovative strategy for PDT, offering enhanced safety and efficacy.
• The integration of natural PSs with lanthanide-based nanoplatforms holds significant promise for overcoming existing PDT challenges.
• Bridging preclinical findings with clinical translation remains a critical future direction for these advanced PDT agents.