2020年9月22日
Photodynamic therapy using LCST polymers exerting pH-responsive isothermal phase transition.
Journal of controlled release : official journal of the Controlled Release Society
- ,
- ,
- ,
- ,
- ,
- 巻
- 328
- 号
- 開始ページ
- 608
- 終了ページ
- 616
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jconrel.2020.09.036
In photodynamic therapy (PDT), the inherent physicochemical properties of a photosensitizer (PS) critically affect its biodistribution and therapeutic outcome as well as side effect. Here, we developed a PS-polymer conjugate displaying isothermal hydrophilic-to-hydrophobic phase transition in response to tumorous acidic pH. The polymer backbone was poly(N-isopropylacrylamide (NIPAAm)/2-aminoisoprpylacrylamide (AIPAAm)) (P(NIPAAm/AIPAAm)), which shows lower critical solution temperature (LCST) of 30 °C. The amine groups in its side chains were converted to hydrophilic acid-labile 2-propionic-3-methylmaleic (PMM) amides, forming poly(NIPAAm/AIPAAm-PMM). The conjugation of PMM moieties drastically increased the LCST of the polymer to 40 °C and displayed hydrophilic character to minimalize unspecific interaction of PS-P(NIPAAm/AIPAAm-PMM) in bloodstream, diminishing potential photosensitivity. The detachment of PMM at tumorous pH lowered the LCST to that of original P(NIPAAm/AIPAAm), permitting hydrophilic-to-hydrophobic transition at a physiological temperature (37 °C). This pH-responsive isothermal phase transition facilitated interaction with the cultured cancer cells, accomplishing 8.1 times-enhanced cellular uptake and strong phototoxicity in a tumorous pH-selective manner. Even in subcutaneous tumor models, our polymer conjugates exhibited efficient tumor accumulation and significantly augmented PDT effect without inducing unfavorable photochemical toxicity to the skin. This study offers a novel concept of PS delivery systems targeting tumorous pH by the use of isothermal phase transition.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.jconrel.2020.09.036
- PubMed ID : 32971200