Synthesis of amphiphilic derivatives of rose bengal and their tumor accumulation.
It is known that the combination of laser light and its sensitizer is effective for noninvasive tumor treatment, referred to as photodynamic therapy. Using the combination of ultrasound and its sensitizer has also been suggested for a similar kind of tumor treatment, referred to as sonodynamic therapy. The purpose of this paper is to obtain such sensitizers accumulating selectively in tumors. Amphiphilic derivatives of rose bengal (RB) were synthesized to add a tumor-accumulating property to RB. One type of the synthesized RB derivatives (RBD3), having an alkyl chain with a branching carboxyl group, was found to be superior in amphiphilicity to the other types. Tumor tissue distribution of the synthesized derivatives in mice bearing colon 26 carcinoma was evaluated. It was found that RBD3s with carbon chain lengths of 12, 14, and 16 had higher concentrations in the tumor tissue than RB by more than 1 order of magnitude, several hours after administration. The concentrations correlated well with their water/1-octanol partition coefficients. Since RB is known to induce in vitro cell damage in combination with either laser light or ultrasound, the newly synthesized amphiphilic RB derivatives may be potentially useful as a tumor-selective sensitizer for both light and ultrasound.
Sugita
Nami
N
Central Research Laboratory, Hitachi, Ltd., 1-280 Higashi-koigakubo, Kokubunji-shi, Tokyo 185-8601, Japan. nami.sugita.mg@hitachi.com
Kawabata
Ken-ichi
K
Sasaki
Kazuaki
K
Sakata
Isao
I
Umemura
Shin-ichiro
S
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D012395:Rose Bengal / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D012395:Rose Bengal