Thermosensitive nanocomposite gel for intra-tumoral two-photon photodynamic therapy

JOURNAL OF CONTROLLED RELEASE

卷:298

Article; Proceedings Paper

Luo, Lei¹  Zhang, Qi¹  Luo, Yonghuang¹  He, Zhonggui²  Tian, Xiaohe^3,4  Battaglia, Giuseppe^3,4,5 

[1] Southwest Univ, Coll Pharmaceut Sci, Minist Educ, Key Lab Luminescent & Real Time Analyt Chem, Chongqing 400715, Peoples R China

[2] Shenyang Pharmaceut Univ, Dept Pharmaceut, Wuya Coll Innovat, Shenyang, Liaoning, Peoples R China

[3] Anhui Univ, Dept Chem, Hefei, Anhui, Peoples R China

[4] UCL, Dept Chem, London, England

[5] UCL, Dept Chem Engn, London, England

关键词: Photodynamic therapy;    Two-photon absorption;    Hydrogel;    Micelles;    Deep penetration;   

DOI  :  10.1016/j.jconrel.2019.01.019

来源: Elsevier

【 摘 要 】

We propose here a new approach to achieve intratumoral near-infrared (NIR) two-photon photodynamic therapy (PDT). We established a composite micellar thermosensitive hydrogel made of clinically approved methoxy poly (ethylene glycol)-polylactide copolymer (mPEG-PDLLA) and Pluronic (F127). The mPEG-PDLLA form micelles that can be loaded with two-photon absorption compound (T1) and photosensitizer (PS), The F127 micelles are liquid at room temperature and while forming an hydrogel at body temperature. This enables an in situ gelification upon injection providing long-term retentio within the tumor. The NIR light is thus upconverted into visible light by T1 and excited PS. The morphology, rheology properties and releasing profiles of hydrogel were fully characterized. The rheology properties and releasing mechanism was investigated. The composite hydrogel showed significant cytotoxicity to 4 T1 murine breast cancer cells upon NIR laser irradiation, while it showed non-significant cytotoxicity without. Time-dependent in vivo and ex vivo distribution results suggested that hydrogel administrated via intratumoral injection could prolong both PDT agents retention in tumor. We show here that the use of NIR radiation allows deep tissue penetration and inhibition of tumor growth of > 50% even under 1 cm thick muscle tissue.

【 授权许可】

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