Photoactive Folic acid nanocomposite for targeted PDT of Breast and liver Cancer cell lines

Allam, Ahmed; Tawfik, Walid; Abo-Elfadl, Mahmoud T.; Fahmy, Ahmed M.; Elfeky, Souad A.

doi:10.21608/ejchem.2025.358951.11281

	Photoactive Folic acid nanocomposite for targeted PDT of Breast and liver Cancer cell lines
Egyptian Journal of Chemistry
Articles in Press, Accepted Manuscript, Available Online from 08 April 2025
Document Type: Original Article
DOI: 10.21608/ejchem.2025.358951.11281
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Authors
Ahmed Allam¹; Walid Tawfik ¹; Mahmoud T. Abo-Elfadl ²^{, 3}; Ahmed M. Fahmy⁴; Souad A. Elfeky¹
¹National Institute of Laser Enhanced Sciences, LAMPA Department, Cairo University, Cairo 12613, Egypt.
²Biochemistry Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, Egypt.
³Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo 12622, Egypt.
⁴Pathology Deptartment., National Cancer Institute, Cairo University, Cairo 12613, Egypt.
Abstract
Cancer is a pervasive global health challenge, with breast and liver cancers being at the forefront. A novel treatment approach involves using chitosan nanocarriers and the photosensitizing agent pheophorbide-a to selectively target and eradicate cancer cells through folic acid (FO)-guided laser activation. Building on our prior breakthroughs in photothermal therapy (PTT) using gold nanorods, this study synthesizes and characterizes Pheophorbide-a@Chitosan-folic acid nanocomposites (Pha@CH-FO NC) for targeted photodynamic therapy (PDT). Results demonstrate synergistic ROS-mediated cytotoxicity in breast and liver cancer cells (IC50: 122.74 µg/mL for MCF7), with apoptosis confirmed via Bcl-2 downregulation (60–70%, p < 0.001). This dual-modal approach, integrating PDT with PTT insights, advances precision oncology. The synthesized Pheophorbide-a@Chitosan nanoparticles conjugated with folic acid (Pha@CH-FO NC) underwent thorough characterization by FTIR, TEM, UV-VIS, and HPLC analyses. Results from MTT assays showed that Pha@CH-FO NC had modest cytotoxicity profiles, with IC50 values of 122.74 µg/mL for MCF7 and 217.27 µg/mL for T-47D. There were no discernible IC50 values for MDA-MB-231 and HepG2 cell lines after a 24-hour incubation period. Moreover, when MCF7 and T-47D cells were exposed to half the IC50 of Pha@CH-FO NC combined with laser irradiation (405 nm, 50 mW/96 seconds), they exhibited 50% cytotoxicity. MDA-MB-231 and HepG2 cells showed comparable effects under laser irradiation of 10 mW/500 seconds. Apoptosis was the predominant mode of cell death in all treated cell lines, as evidenced by a decrease in Bcl-2 gene expression (an apoptosis-suppressing gene) in treated cell lines compared to controls. Additionally, increased production of reactive oxygen species (ROS) was observed in irradiated MCF7 and T-47D cells at 50 mW/96 seconds, MDA-MB-231 cells at 50 mW/200 seconds, and HepG2 cells at 10 mW/1000 seconds. This study highlights the potential of Pha@CH-FO NC in enhancing PDT effectiveness and inhibiting cancer progression, making it a crucial component in targeted cancer therapies. The evaluation of various photodynamic approaches underscores the potential of this novel photoactive NC system in advancing PDT and cancer treatment paradigms.
Keywords
Photodynamic Therapy (PDT); Folic Acid-Conjugated; Nanocomposite. Breast Cancer treatment; Liver Cancer treatment; Chitosan Nanoparticles; Pheophorbide-a; Reactive Oxygen Species (ROS)


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