Background
Chlorin e6(Ce6) is a second-generation photosensitizer. Compared to the first-generation photosensitizers, Chlorin e6 has the advantage of efficiently absorbing longer light wavelengths, which is favorable for deeper tissue penetration[1] .Chlorin e6-based photosensitizers are widely used in antitumor photodynamic therapy(PDT) due to high quantum output of single oxygen and a strong absorption band in a red region[2]
Chlorin e6-mediated PDT inhibits adipocyte differentiation and lipogenesis via regulating AMPK in 3T3-L1 cells, indicated that Chlorin e6-mediated PDT might serve as a potential therapy for the treatment of obesity and obesity-associated diseases[2]. Chlorin e6-Fu/AL@GG hydrogel can be a feasible nanocarrier for Chlorin e6-assisted PDT that possesses an excellent capability to selectively kill colon cancer cells[3]
Chlorin e6-loaded PEG-PCL nanoemulsions (Ce6-PCL-NEs) showed efficient cellular uptake and, upon laser irradiation, generated singlet oxygen to kill tumor cells. Particularly, Chlorin e6-PCL-NEs showed prolonged blood circulation and about 60% increased tumor accumulation compared to free Chlorin e6 after intravenous injection to 4T1 tumor-bearing mice(2.5mg/kg), indicated the promising potential of Chlorin e6-PCL-NEs for efficient PDT and in vivo drug delivery to tumor tissue[4]. Chlorin e6 nano-precipitations (Chlorin e6 NPs) can be prepared by a one-pot method for effective photodynamic therapy of colorectal cancer. The HT-29 tumour-bearing mice were randomly divided into three groups and were administered intravenously with saline, free Chlorin e6 and Chlorin e6 NPs (5mg/kg Chlorin e6) once every 2 days for 2 weeks. The laser was applied three times 24h post injection (680 nm, 0.5 W/cm2 for 5 min). Chlorin e6 NPs showed significantly enhanced anticancer benefits compared to free Chlorin e6, which almost obtained full ablation of tumours at the end of the study[5]
参考文献:
[1].Ryu AR, Kim YW, et al. Chlorin e6-mediated photodynamic therapy modulates adipocyte differentiation and lipogenesis in 3T3-L1 cells. Photodiagnosis Photodyn Ther. 2020;31:101917.
[2].Papayan G.V., Akopov А.L. Photodynamic theranostics of central lung cancer: capabilities of early diagnosis and minimally invasive therapy (review). Sovremennye tehnologii v medicine 2021; 13(6): 78
[3].Karuppusamy S, Hyejin K, et al. Nanoengineered chlorin e6 conjugated with hydrogel for photodynamic therapy on cancer. Colloids Surf B Biointerfaces. 2019;181:778-788.
[4].Park C, Yoo J, et al. Chlorin e6-Loaded PEG-PCL Nanoemulsion for Photodynamic Therapy and In Vivo Drug Delivery. Int J Mol Sci. 2019;20(16):3958. Published 2019 Aug 14.
[5].Miao Z, Wang Y, et al. One-pot synthesis chlorin e6 nano-precipitation for colorectal cancer treatment Ce6 NPs for colorectal cancer treatment. IET Nanobiotechnol. 2021;15(8):680-685.
Chlorin e6(Ce6) 是第二代光敏剂。与第一代光敏剂相比，Chlorin e6具有高效吸收更长波长光的优势，有利于更深的组织穿透[1]。基于Chlorin e6的光敏剂广泛应用于抗肿瘤光动力治疗(PDT) 由于单氧的高量子输出和红色区域的强吸收带[2]
Chlorin e6 介导的 PDT 通过调节 3T3-L1 细胞中的 AMPK 抑制脂肪细胞分化和脂肪生成，表明 Chlorin e6 介导的 PDT 可能作为治疗肥胖和肥胖相关疾病的潜在疗法[2 ]。 Chlorin e6-Fu/AL@GG 水凝胶可作为 Chlorin e6 辅助 PDT 的纳米载体，具有出色的选择性杀死结肠癌细胞的能力[3]
负载二氢卟酚 e6 的 PEG-PCL 纳米乳剂 (Ce6-PCL-NEs) 显示出有效的细胞摄取，并且在激光照射下产生单线态氧以杀死肿瘤细胞。特别是，在静脉注射给 4T1 荷瘤小鼠（2.5mg/kg）后，与游离的 Chlorin e6 相比，Chlorin e6-PCL-NEs 显示出延长的血液循环和约 60% 的肿瘤积累，表明 Chlorin e6-PCL-用于有效 PDT 和体内药物递送至肿瘤组织的 NEs[4]。可通过一锅法制备二氢卟酚 e6 纳米沉淀物 (Chlorin e6 NPs)，用于结直肠癌的有效光动力治疗。 HT-29 荷瘤小鼠随机分为三组，每 2 天一次静脉注射生理盐水、游离 Chlorin e6 和 Chlorin e6 NPs (5mg/kg Chlorin e6)，持续 2 周。注射后 24 小时应用激光 3 次（680 nm，0.5 W/cm2，持续 5 分钟）。与游离的 Chlorin e6 相比，Chlorin e6 NPs 显示出显着增强的抗癌益处，后者在研究结束时几乎完全消融了肿瘤[5]
Protocol
| Cell experiment [1]: |
|
Cell lines
|
Human alveolar adenocarcinoma cells A549
|
|
Preparation Method
|
The 96-well plates were treated with 50μL of agar solution (1.5%(w/v)) made in serum free Dulbecco’s Modified Eagle’s Medium. A549 cells(1×104/well) were seeded in 96-well plates, centrifuged at 1500rcf for 15min at 25℃. The spheroids of 400-500μm size obtained after 4-5 days were utilized for the study
|
|
Reaction Conditions
|
3μg/mL for 4h(Growth Inhibition, Live/Dead Cell Assay), a serial concentration for 12h(0.5-3μg/mL In Vitro Phototoxicity)
|
|
Applications
|
A549 3D spheroids treated with Chlorin e6 micelles showed significant inhibition in growth, enhanced phototoxicity, and cellular apoptosis in comparison to free Chlorin e6.
|
| Animal experiment [2]: |
|
Animal models
|
SCC-7 tumor-bearing mice（1×106 SCC-7 cells(80μL) were injected into the left femoral regions of 4-week-old C3H/HeN male mice）
|
|
Preparation Method
|
Free Chlorin e6, and gelatin-Chlorin e6 solution were injected into the tail vein when the tumor volume reached approximately 150±30mm3. At 4 and 12h after the sample injection, the tumor site of each mouse was irradiated with a red laser (658nm, 0.3W, 200J). Then, the tumor sizes of all mice were monitored over 14 days.
|
|
Dosage form
|
Free Chlorin e6, gelatin-Ce6 2μM, or gelatin-Ce6 8μM solution, each containing 2.5mg/kg of Chlorin e6
|
|
Applications
|
In vivo tumor accumulation of gelatin-Chlorin e6-2 was much higher than that of free Chlorin e6 or gelatin-Chlorin e6-8 after intravenous injection into mice. After laser irradiation to the tumor site, gelatin-Chlorin e6-2 showed superior tumor suppression, indicating an enhanced PDT effect.
|
|
参考文献:
[1]. Kumari P, Paul M, et al. Chlorin e6 Conjugated Methoxy-Poly (Ethylene Glycol)-Poly(D,L-Lactide) Glutathione Sensitive Micelles for Photodynamic Therapy. Pharm Res. 2020;37(2):18. Published 2020 Jan 2.
[2]. Son J, Yi G, et al. Gelatin-chlorin e6 conjugate for in vivo photodynamic therapy. J Nanobiotechnology. 2019;17(1):50. Published 2019 Apr 5.
|
没有评价数据