REVIEW 46 wileyonlinelibrary.com © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.particle-journal.com www.MaterialsViews.com Light Harvesting and Photoemission by Nanoparticles for Photodynamic Therapy Amaia Garaikoetxea Arguinzoniz, Emmanuel Ruggiero, Abraha Habtemariam, Javier Hernández-Gil, Luca Salassa, and Juan C. Mareque-Rivas* 1. Introduction The use of photodynamic therapy (PDT) puts light harvesting and delivery to the forefront of arsenals at the disposal of modern medicine for the fight against cancer and other malignancies. The clinical use of PDT involves the use of a photosensitizer (PS) that needs to be excited by light with the appropriate wavelength and exerts its cytotoxic effect through oxygen-mediated processes. [1–4] The advantages of PDT over chemo- or radiotherapies are that it is very rapid, minimally invasive, can be locally applied onto a specific area by selective irradiation, and can be repeated as often as required. A major drawback of PDT is that it needs to use poor tissue-penetrating light (i.e., visible or UV light) for the activation of the PS drug. Hence, the use of PDT is mostly limited to surface tumors such as skin and the treatment of large or deep-seated tumors is severely hampered. In addi- tion, UV and intense visible light are toxic to normal tissue and the few approved PS drugs show limited tumor specificity, which cause side effects. Consequently, a significant effort is cur- rently devoted to develop new PDT method- ologies that can utilize near infrared (NIR) (700–1000 nm) light, as it offers deep tissue penetration wavelength in the “transparency window” and exhibits low toxicity to normal cells and tissue. [5,6] In the past few decades, nanomaterials have demonstrated propitious features for delivering therapeutic molecules effec- tively to diseased sites, including optimum sizes and shapes, and surfaces, which can be decorated with targeting ligands and exploited multivalent interactions. [7] However, some nano- materials have intrinsic physicochemical properties, which can be harnessed to trigger light-induced reactions. In this way, the nanoparticles (NPs) can convert inert chemical compounds to active cytotoxic species in a spatially and temporally controlled manner to damage or destroy the malignant tissues. In recent years, a promising strategy being pursued involves the use of quantum dots (QDs) and upconverting nanoparticles (UCNP) that can harvest and convert low-energy light into elec- trons or visible/UV light, thereby facilitating the transformation of PDT into a viable methodology for the treatment of inacces- sible lesions. Importantly, these nanoscale antennas can also be exploited as nanoplatforms for delivery of the PS or photoactivat- able prodrugs to specific tissues and cellular compartments and for imaging the effect of the treatment using multimodal approaches. QDs are fluorescent nanocrystals composed of semicon- ductor materials that are characterized by broad excitation This review provides an overview of recent efforts to utilize light harvesting and photoemission by nanoparticles (NPs) for photodynamic therapy (PDT) applications. In particular, it focuses on the recent use of quantum dots (QDs) and upconverting nanophosphors (UCNPs), which over the past decade have captivated considerable interest in biomedical research as new classes of fluo- rescent probes for in vivo biomolecular and cellular imaging. Increasingly, the unique properties of QDs and UCNPs are becoming the focus of attention in PDT as an emerging cancer treatment modality where a photosensitizer mol- ecule (PS) exposed to light of a wavelength matching its absorption spectrum mediates cytotoxic effects. An overview of the processes and approaches that have been used to induce and optimize photoinduced energy and charge transfer processes and generation of different cytotoxic species ranging from reactive oxygen species to inorganic metal-based drugs using these NPs, as well as for their targeted delivery in a cell- or tissue-specific manner is pre- sented. The main challenge for nanomaterials entering mainstream clinical practice is understanding and overcoming their toxicity. Hence, some of the known mechanisms by which QDs and UCNPs can cause unwanted toxicity are briefly reviewed, as well as how they can be minimized. DOI: 10.1002/ppsc.201300314 A. Garaikoetxea Arguinzoniz, E. Ruggiero, Dr. A. Habtemariam, J. Hernández-Gil, Dr. L. Salassa, J. C. Mareque-Rivas Cooperative Centre for Research in Biomaterials (CIC biomaGUNE) 20009 San Sebastián, Spain Fax: (+34) 943 005301 E-mail: jmareque@cicbiomagune.es A. Habtemariam Department of Chemistry University of Warwick Coventry CV4 7AL, UK A. Habtemariam, Prof. J. C. Mareque-Rivas Ikerbasque, Basque Foundation for Science 48011 Bilbao, Spain J. C. Mareque-Rivas Departmento de Bioquímica y Biología Molecular Universidad del Pais Vasco 48940 Leioa, Spain Part. Part. Syst. Charact. 2014, 31, 46–75