Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy

氯 e6-pHLIP <候补选手class=“ a-plus-plus ”> ss -AuNRs,金使nanorod具有感光性结合包含 pH (低)有给予细胞外的 pH 的一张二硫化物契约的插入肽( pHLIP )( pH <候补选手class=“ a-plus-plus ”> e )-driven 肿瘤指向能力，成功地为光力学的 bimodal 和 photothermal 治疗被开发了。在这 bimodal 治疗，氯 e6 (Ce6 ) ，第二代的 photosensitizer (PS ) ，被用于光力学的治疗(太平洋夏季时间) 。金 nanorods (AuNRs ) 作为 Ce6 的 nanocarrier 和 quencher 为 photothermal 治疗(PTT ) 并且也被用作一个过高热代理人。pHLIPss 作为一根驾驶 pHe 的指向探针被设计在低 pH 在癌症房间提高 Ce6 和 AuNRs 的累积。在 Ce6-pHLIP < 潜水艇 class= “ a-plus-plus ” > ss -AuNRs, Ce6 接近并且由 AuNRs 熄灭了，引起小太平洋夏季时间效果。当暴露了到正常生理的 pH 时 7.4， Ce6-pHLIP < 潜水艇 class= “ a-plus-plus ” > ss -AuNRs 泛泛地与房间膜联系。然而，曾经暴露了到酸的 pH 6.2， pHLIP 活跃地插入到房间膜，和 conjugates 是进房间的 translocated。当这发生时， Ce6 由于二硫化物与 AuNRs 分开细胞内部的谷胱甘肽(GSH ) 引起的契约劈开，和汗衫氧在光之上为太平洋夏季时间被生产照耀。作为单个 PTT 代理人，另外， AuNRs 能由提高的浸透和保留(EPR ) 效果在肿瘤提高 PS 的累积。因此由我们的数据显示了当暴露了到酸的 pH 时， Ce6-pHLIP < 潜水艇 class= “ a-plus-plus ” > ss -AuNRs 能为癌症治疗完成 synergistic PTT/PDT bimodality。

Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.