Kwang Poo Chang ^1* Joseph M. Reynolds ² Dennis Ng ³ Jordy Y. Tu ⁴ Chia-Kwung Fan ⁴ Shin-Hong Shiao ⁵

• ¹ Microbiology/Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States
• ² Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States
• ³ Department of Chemistry, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong Region, China
• ⁴ Department of Molecular Parasitology and Tropical Diseases, School of Medicine, Taipei Medical University, Taipei, Taiwan
• ⁵ Department of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Department of Tropical Medicine and parasitology, School of medicine, National Taiwan University, Taipei, Taiwan

Singlet oxygen ( 1 O2) is a potent biocide potentially deployable for integrated control of tropical diseases and their insect vectors. This very short-lived free radial is highly destructive of cellular molecules when generated intracellularly. Most organisms, including parasites and vectors, are defenseless against 1 O2 with the exception of plants, which produce it abundantly during photosynthesis, hence acquisition of specific mechanisms for its detoxification. In the presence of O2 under physiological conditions, certain dyes or photosensitizers (PS), e.g. porphyrins and phthalocyanines (PC), are excitable by light to produce biocidal 1 O2. Its half-life is in the order of µs, necessitating its intracellular generation in order to harness its biocidal activity most effectively. This is achievable by loading cells with PS for excitation with light to produce 1 O2 in situ. One example to achieve this is genetic engineering of Leishmania to complement its inherent defects in porphyrin biosynthesis, resulting in cytosolic accumulation of abundant PS in the form of uroporphyrin 1 (URO). Another example is chemical engineering of PC for hydrophilicity, thereby facilitating the endocytosis of such PS by cells. Leishmania loaded with cytosolic URO and endosomal PC are inactivated by the 1 O2 produced via light-activation of these PS in the two different cell compartments. The inactivated Leishmania are non-viable, but have their natural vaccines and adjuvants well-preserved for prophylactic vaccination against experimental leishmaniasis. 1 O2 -inactivated Leishmania is potentially useful to serve as a platform for safe and effective delivery of transgenically add-on vaccines against malignant and viral diseases in experimental models. Hydrophilic and cationic PC were also shown experimentally to act as a new type of dim light-activatable insecticides, i.e. their mosquito larvicidal activities with <µM LD50 values. Similar results are expected by studying PC in additional laboratory insect models. A significant advantage has long been attributed to this type of insecticides, i.e. their aversion to selection of genetic variants for resistance. An additional advantage of PC is their excitability to produce insecticidal 1 O2 with deep-penetrating red or infrared light invisible to most insects, thereby potentially increasing the range and scope of targetable insect vectors.