Gold-Enhanced Lanthanide Nanomedicine for Near-Infrared Photodynamic Therapy.

Cancer remains a major global health challenge due to its high morbidity and mortality rates. Traditional treatments, such as surgery, radiotherapy, and chemotherapy, have some clear limitations, which is why there is a growing need for innovative therapeutic modalities. One precise targeting of tumors with few side effects can be achieved through a promising modality called photodynamic therapy (PDT). PDT is a noninvasive cancer treatment that uses photosensitizers to produce cytotoxic species that selectively kill cancer cells under light exposure. In recent years, a variety of nanoparticles (NPs) have been developed. Among them, gold-doped lanthanide NPs (Au-Ln NPs) stand out as a significant advancement in PDT due to the integration of the surface plasmon resonance (LSPR) properties of AuNPs and upconversion (UC) luminescence of Ln NPs. In this perspective, we review various synthesis methods for upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs), highlighting their integration into multifunctional Au-Ln NPs for enhanced PDT. By using near-infrared (NIR) light, Au-Ln UCNPs can penetrate deep into tissues, making them particularly effective for treating deeply seated tumors. However, the synthesis of Au-Ln NPs comes with its own challenges. The main challenges include the uniform distribution of gold doping, the control of the particle size and shape, and the reproducibility as well as scalability. Overcoming these challenges for controlled synthesis and enhanced PDT will be critical. Correspondingly, their PDT applications are discussed in vitro and in vivo. Lastly, the current challenges, limitations, and future prospects will be explored.