二氢卟吩e6光动力学疗法对人舌鳞癌细胞株Tca8113的杀伤作用

目的:探讨二氢卟吩e6(Ce6)光动力学疗法(Ce6-PDT)对体外培养人舌鳞癌Tca8113细胞的杀伤作用。方法:向体外培养的人舌鳞癌Tca8113细胞中加入Ce6,浓度分别为5、10、20、50和100μg/ml,孵育1.5h,予波长630 nm半导体激光照射,照射的功率密度为100mW/cm2,能量密度分别为0.5、1、2、5、10和15J/cm2,继续孵育6h,用MTS比色法测定细胞存活率。结果:(1)不受光照的条件下,较低浓度Ce6(<10μg/ml)与细胞共同培养而对细胞的毒性较小,Ce6浓度为20μg/ml时对细胞的杀伤率约为10%。(2)光照条件下,Ce6-PDT能有效地杀伤体外培养的人舌鳞癌Tca8113细胞,其杀伤作用与Ce6浓度及光照剂量正相关,呈浓度/剂量依赖性(P<0.01)。结论:Ce62PDT能有效地杀伤体外培养的人舌鳞癌Tca8113细胞;Ce6在较大浓度下对细胞有毒性。

Ce6 nanoassemblies:Molecular mechanism and strategies for combinational anticancer therapy Special Collection:Aggregation-Induced Processes and Functions

Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood-brain barrier

Glioblastoma(GBM)is the most aggressive malignant brain tumor and has a high mortality rate.Photodynamic therapy(PDT)has emerged as a promising approach for the treatment of malignant brain tumors.However,the use of PDT for the treatment of GBM has been limited by its low blood-brain barrier(BBB)permeability and lack of cancer-targeting ability.Herein,brain endothelial cell-derived extracellular vesicles(bEVs)were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB.To enhance PDT efficacy,the photosensitizer chlorin e6(Ce6)was linked to mitochondria-targeting triphenylphosphonium(TPP)and entrapped into bEVs.TPPconjugated Ce6(TPP-Ce6)selectively accumulated in the mitochondria,which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation.Moreover,the encapsulation of TPP-Ce6 into b EVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6,leading to significantly enhanced PDT efficacy in U87MG GBM cells.An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that b EVs containing TPP-Ce6[b EV(TPP-Ce6)]substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis.As such,b EV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity,suggesting that mitochondria are an effective target for photodynamic GBM therapy.

Formation of plasmon quenching dips greatly enhances ^1O2 generation in a chlorin e6-gold nanorod coupled system

Photodynamic therapy （PDT）, as a noninvasive therapeutic method, has been actively explored recently for cancer treatment. However, owing to the weak absorption in the optically transparent windows of biological tissues, most com- mercial photosensitizers （PSs） exhibit low singlet oxygen （^1O2） quantum yields when excited by light within this window. Finding the best way to boost ^1O2 production for clinical applications using light sources within this window is, thus, a great challenge. Herein, we tackle this problem using plasmon resonance energy transfer （PRET） from plasmonic nanoparticles （NPs） to PSs and demonstrate that the formation of plasmon quenching dips is an effective way to enhance ^1O2 generation. The combination of the photosensitizer chlorin e6 （Ce6） and gold nanorods （AuNR） was employed as a model system. We observed a clear quenching dip in the longitudinal surface plasmon resonance （LSPR） band of the AuNRs when the LSPR band overlaps with the Q band of Ce6 and the spacing between Ce6 and the rods is within the acting distance of PRET. Upon irradiation with 660 nm continuous-wave laser light, we obtained a seven-fold enhancement in the ^1O2 signal intensity compared with that of a non-PRET sample, as determined using the ^1O2 electron spin resonance probe 2,2,6,6-tetramethyl-4-piperidine （TEMP）. Furthermore, we demonstrated that the PRET effect is more efficient in enhancing ^1O2 yield than the often-employed local field enhancement effect. The effectiveness of PRET is further extended to the in vitro level. Considering the flexibility in manipulating the localized SPR properties of plasmonic nanoparticles/nanostructures, our findings suggest that PRET-based strategies may be a general way to overcome the deficiency of most commercial organic PSs in biological optically transparent windows and promote their applications in clinical tumor treatments.

New approaches to diagnostics and treatment of cholangiocellular cancer based on photonics methods

Cholangiocellular cancer(CCC)is an oncological disease of the bile ducts characterized by a high mortality rate.To date,the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease.This work presents the results of fluorescence diagnostics(FD),which consists in using a modified optical fiber and photodynamic therapy(PDT)using a therapeutic laser instead of a low-intensity laser.This technique was tested on 43 patients in a clinical setting.The results obtained indicate a direct correlation between spectroscopic and video FD methods.Furthermore,a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer,with the commercial names of PhotoIon Radachlorin and Photoran and stricture regression.Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer,which results in a significant reduction of the operation time without decreasing its effectiveness.

An effective method to generate controllable levels of ROS for the enhancement of HUVEC proliferation using a chlorin e6-immobilized PET film as a photo-functional biomaterial

Reactive oxygen species(ROS)are byproducts of cellular metabolism;they play a significant role as secondary messengers in cell signaling.In cells,high concentrations of ROS induce apoptosis,senescence,and contact inhibition,while low concentrations of ROS result in angiogenesis,proliferation,and cytoskeleton remodeling.Thus,controlling ROS generation is an important factor in cell biology.We designed a chlorin e6(Ce6)-immobilized polyethylene terephthalate(PET)film(Ce6-PET)to produce extracellular ROS under red-light irradiation.The application of Ce6-PET films can regulate the generation of ROS by altering the intensity of light-emitting diode sources.We confirmed that the Ce6-PET film could effectively promote cell growth under irradiation at 500 μW/cm^(2) for 30 min in human umbilical vein endothelial cells.We also found that the Ce6-PET film is more efficient in generating ROS than a Ce6-incorporated polyurethane film under the same conditions.Ce6-PET fabrication shows promise for improving the localized delivery of extracellular ROS and regulating ROS formation through the optimization of irradiation intensity.