期刊
JOURNAL OF CONTROLLED RELEASE
卷 328, 期 -, 页码 608-616出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.09.036
关键词
Photodynamic therapy; Photosensitizer; pH-selective delivery; PNIPAAm; Isothermal phase transition
资金
- Science and Technology Platform Program for Advanced Biological Medicine from Japan Agency for Medical Research and Development (AMED) [JP19am0401018]
- Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED [JP19cm0106202]
- Center of Innovation (COI) program from Japan Science and Technology Agency (JST)
- JSPS KAKENHI [JP15H04635, JP16K15104, JP18H04163, JP26882022, JP20K20196]
- Kobayashi International Scholarship Foundation
- Fivestar Alliance from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Indonesia Endowment Fund for Education (LPDP) Scholarship
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 degrees 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 degrees 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 degrees 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据