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]
參考文獻(xiàn):
[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) 是第二代光敏劑。與第一代光敏劑相比,Chlorin e6具有高效吸收更長波長光的優(yōu)勢,有利于更深的組織穿透[1]。基于Chlorin e6的光敏劑廣泛應(yīng)用于抗腫瘤光動力治療(PDT) 由于單氧的高量子輸出和紅色區(qū)域的強(qiáng)吸收帶[2]
Chlorin e6 介導(dǎo)的 PDT 通過調(diào)節(jié) 3T3-L1 細(xì)胞中的 AMPK 抑制脂肪細(xì)胞分化和脂肪生成,表明 Chlorin e6 介導(dǎo)的 PDT 可能作為治療肥胖和肥胖相關(guān)疾病的潛在療法[2 ]。 Chlorin e6-Fu/AL@GG 水凝膠可作為 Chlorin e6 輔助 PDT 的納米載體,具有出色的選擇性殺死結(jié)腸癌細(xì)胞的能力[3]
負(fù)載二氫卟酚 e6 的 PEG-PCL 納米乳劑 (Ce6-PCL-NEs) 顯示出有效的細(xì)胞攝取,并且在激光照射下產(chǎn)生單線態(tài)氧以殺死腫瘤細(xì)胞。特別是,在靜脈注射給 4T1 荷瘤小鼠(2.5mg/kg)后,與游離的 Chlorin e6 相比,Chlorin e6-PCL-NEs 顯示出延長的血液循環(huán)和約 60% 的腫瘤積累,表明 Chlorin e6-PCL-用于有效 PDT 和體內(nèi)藥物遞送至腫瘤組織的 NEs[4]。可通過一鍋法制備二氫卟酚 e6 納米沉淀物 (Chlorin e6 NPs),用于結(jié)直腸癌的有效光動力治療。 HT-29 荷瘤小鼠隨機(jī)分為三組,每 2 天一次靜脈注射生理鹽水、游離 Chlorin e6 和 Chlorin e6 NPs (5mg/kg Chlorin e6),持續(xù) 2 周。注射后 24 小時應(yīng)用激光 3 次(680 nm,0.5 W/cm2,持續(xù) 5 分鐘)。與游離的 Chlorin e6 相比,Chlorin e6 NPs 顯示出顯著增強(qiáng)的抗癌益處,后者在研究結(jié)束時幾乎完全消融了腫瘤[5]
| Cell experiment [1]: | |
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Cell lines |
Human alveolar adenocarcinoma cells A549 |
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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 |
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Reaction Conditions |
3μg/mL for 4h(Growth Inhibition, Live/Dead Cell Assay), a serial concentration for 12h(0.5-3μg/mL In Vitro Phototoxicity) |
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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]: | |
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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) |
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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. |
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Dosage form |
Free Chlorin e6, gelatin-Ce6 2μM, or gelatin-Ce6 8μM solution, each containing 2.5mg/kg of Chlorin e6 |
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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. |
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參考文獻(xiàn): [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. |
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