Far-red light activatable, multifunctional prodrug for fluorescence optical imaging and combinational treatment.
We recently developed "photo-unclick chemistry", a novel chemical tool involving the cleavage of aminoacrylate by singlet oxygen, and demonstrated its application to visible light-activatable prodrugs. In this study, we prepared an advanced multifunctional prodrug, Pc-(L-CA4)2, composed of the fluorescent photosensitizer phthalocyanine (Pc), an SO-labile aminoacrylate linker (L), and a cytotoxic drug combretastatin A-4 (CA4). Pc-(L-CA4)2 had reduced dark toxicity compared with CA4. However, once illuminated, it showed improved toxicity similar to CA4 and displayed bystander effects in vitro. We monitored the time-dependent distribution of Pc-(L-CA4)2 using optical imaging with live mice. We also effectively ablated tumors by the illumination with far-red light to the mice, presumably through the combined effects of photodynamic therapy (PDT) and released chemotherapy drug, without any sign of acute systemic toxicity.
Department of Pharmaceutical Sciences and ‡Department of Chemistry and Biochemistry, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73117, United States.
Moses
M
Bio
Pallavi
P
Rajaputra
Gregory
G
Nkepang
Youngjae
Y
You
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001632:Bibenzyls / Q000494:pharmacology; D024201:Bystander Effect; D005453:Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry
D000970:Antineoplastic Agents; D001632:Bibenzyls; D008823:Micelles; D017319:Photosensitizing Agents; D011355:Prodrugs; D014404:Tubulin; C040105:combretastatin