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 b...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.展开更多
Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibi...Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibility. In this work, we fabricate an interesting type of MSNs which are intrinsically doped with photosensitizing molecules, chlorin e6 （Ce6）. By increasing the amount of Ce6 doped inside the silica matrix, it is found that the morphology of MSNs changes from spheres to rod-like shapes. The obtained Ce6-doped mesoporous silica nanorods （CMSNRs） are not only able to produce singlet oxygen for photodynamic therapy, but can also serve as a drug delivery platform with high drug loading capacity by utilizing their mesoporous structure. Compared to spherical nano- particles, it is found that CMSNRs with a larger aspect ratio show much faster uptake by cancer cells. With doxorubicin （DOX） employed as a model drug, the combined photodynamic and chemotherapy is carried out, achieving synergistic anti-tumor effects both in vitro and in vivo. Our study presents a new design of an MSN-based drug delivery platform, which intrinsically is fluorescent and able to serve as a photodynamic agent, promising for future imaging-guided combination therapy of cancer.展开更多
文摘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.
基金This work was partially supported by the National Basic Research Programs of China （973 Program） （Nos. 2012CB932600 and 2011CB911002）, the National Natural Science Foundation of China （Nos. 51222203 and 51132006）, Jiangsu Key Laboratory for Carbon- Based Functional Materials and Devices, a Jiangsu Natural Science Fund for Distinguished Young Scholars, and a Project Funded by the Priority Academic Program Development （PAPD） of Jiangsu Higher Education Institutions.
文摘Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibility. In this work, we fabricate an interesting type of MSNs which are intrinsically doped with photosensitizing molecules, chlorin e6 （Ce6）. By increasing the amount of Ce6 doped inside the silica matrix, it is found that the morphology of MSNs changes from spheres to rod-like shapes. The obtained Ce6-doped mesoporous silica nanorods （CMSNRs） are not only able to produce singlet oxygen for photodynamic therapy, but can also serve as a drug delivery platform with high drug loading capacity by utilizing their mesoporous structure. Compared to spherical nano- particles, it is found that CMSNRs with a larger aspect ratio show much faster uptake by cancer cells. With doxorubicin （DOX） employed as a model drug, the combined photodynamic and chemotherapy is carried out, achieving synergistic anti-tumor effects both in vitro and in vivo. Our study presents a new design of an MSN-based drug delivery platform, which intrinsically is fluorescent and able to serve as a photodynamic agent, promising for future imaging-guided combination therapy of cancer.
