Novel Chlorin e6-Curcumin Derivatives as a Potential Photosensitizer: Synthesis, Characterization, and Anticancer Activity

Abstract

Novel series of chlorin e6-curcumin derivatives were designed and synthesized. All the synthesized compounds 16, 17, 18, and 19 were tested for their photodynamic treatment (PDT) efficacy against human pancreatic cancer cell lines: AsPC-1, MIA-PaCa-2, and PANC-1. The cellular uptake study was performed in the aforementioned cell lines using fluorescence-activated cell sorting (FACS). 17, among the synthesized compounds with IC50 values of 0.27, 0.42, and 0.21 µM against AsPC-1, MIA PaCa-2, and PANC-1 cell lines, respectively, demonstrated excellent cellular internalization capability and exhibited higher phototoxicity relative to the parent Ce6. The quantitative analyses using Annexin V-PI staining revealed that the 17-PDT-induced apoptosis was dose-dependent. In pancreatic cell lines, 17 reduced the expression of the anti-apoptotic protein, Bcl-2, and increased the pro-apoptotic protein, cytochrome C, which indicates the activation of intrinsic apoptosis, the primary cause of cancer cell death. Structure–activity relationship studies have shown that the incorporation of additional methyl ester moiety and conjugation to the enone moiety of curcumin enhances cellular uptake and PDT efficacy. Moreover, in vivo PDT testing in melanoma mouse models revealed that 17-PDT greatly reduced tumor growth. Therefore, 17 might be an effective photosensitizer for PDT anticancer therapy.

Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy

“…The Ce6 was prepared by dissolving in normal saline as a vehicle for intravenous drug administration. Mice were incubated for 3 h as per the protocol suggested by our previous paper [ 23 , 24 ], and tumors were irradiated with a laser of 660 nm. The absorption spectrum of oxyhemoglobin, deoxyhemoglobin, and Ce6 is plotted in Figure 9 b.…”

“…Photodynamic therapy (PDT) has emerged as one of the most promising treatment options for pancreatic cancers [ 20 , 21 , 22 , 23 , 24 ]. The treatment approach of PDT relies on the generation of reactive oxygen species (ROS) and their subsequent toxic effects after the excitation of photosensitizer (PS) by using light of a specific wavelength in the targeted region [ 25 , 26 ].…”

“…A well-known PS, Ce6 [ 58 , 59 , 60 ] has been used together with the light of a 660 nm wavelength having a power of 200 mW/cm 2 . Ce6, a second-generation photosensitizer, has been extensively studied for treating different types of cancer, such as pancreatic, skin, colon, and ovarian cancer [ 23 , 61 , 62 ]. However, very little research about the underlying vascular mechanism of Ce6-mediated PDT encouraged us to study its vascular shutdown efficacy utilizing the WGS-PAM system.…”

Dual regulation of osteosarcoma hypoxia microenvironment by a bioinspired oxygen nanogenerator for precise single-laser synergistic photodynamic/photothermal/induced antitumor immunity therapy

“…The conventional paradigm of PDT hinges on the cytotoxic impact induced by a photosensitizer under the irradiation of light, which catalyzes the transformation of molecular oxygen (O 2 ) into reactive oxygen species (ROS) [ 11 ]. These ROS, in turn, orchestrate cellular demise and the ensuing destruction of the tumor cells.…”

Putting a “C60 Ball” and Chain to Chlorin e6 Improves Its Cellular Uptake and Photodynamic Performances

“…The penetration of a photosensitizer into the cell is a crucial step to perform an efficient PDT treatment. To bypass this drawback, many Ce6 derivatives [ 3 , 4 , 5 , 16 , 17 , 18 , 19 , 20 ] and ad hoc delivery systems [ 3 , 4 , 5 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] were developed, aiming to improve Ce6 accumulation in cancer cells through passive and active targeting.…”