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. 2025 Aug;24(8):1373-1392.
doi: 10.1007/s43630-025-00764-1. Epub 2025 Jul 21.

Unveiling role of serum albumin in disaggregation and cellular delivery of a near-infrared chlorophyll-based photosensitizer in breast cancer cells

Sucharita Chatterjee  1   2 , Alok Dube  3   4 , Shovan Kumar Majumder  1   2
Affiliations

Unveiling role of serum albumin in disaggregation and cellular delivery of a near-infrared chlorophyll-based photosensitizer in breast cancer cells

Sucharita Chatterjee et al. Photochem Photobiol Sci. 2025 Aug.

Abstract

The efficacy of photosensitizer (PS) for photodynamic therapy of malignant tumors depends significantly on its interaction with serum proteins. Albumin binds non-covalently with hydrophilic and amphiphilic PSs. However, a clear understanding on role of albumin in delivery of PS in cancer cells is still lacking. We explored the role of albumin in disaggregation and cellular uptake of Cycloimide Purpurin-18 (CIPp-18), an amphiphilic near-infrared PS, in human breast carcinoma (MCF-7) cells. Results show that CIPp-18 added to fetal bovine serum (FBS) associates mainly with albumin and its aggregation in neat buffer is completely reversed by addition of bovine serum albumin (BSA). Under serum-enriched condition, CIPp-18 accumulated efficiently in cells and localized mainly in cell membrane and ER but not in lysosomes. Accumulation of CIPp-18 in cells was not affected by inhibitors of metabolic energy but partially inhibited at cold temperature. Confocal microscopy studies on uptake of CIPp-18 complexed to FITC-labeled BSA revealed significant colocalization of CIPp-18 and FITC-BSA in the distinct regions of cell membrane at 15 min after incubation, whereas at 90 min, FITC albumin localized independently in endocytic vesicles. Studies on binding of CIPp-18 with albumin using intrinsic tryptophan fluorescence of BSA and in silico docking reveal that CIPp-18 binds near Sudlow site I but away from tryptophan residue. Significant quenching of fluorescence of BSA-bound CIPp-18 by iodide ions further confirms that CIPp-18 binds at the surface of albumin. These results together demonstrate that the cellular uptake of albumin-bound CIPp-18 is mediated via facilitated diffusion involving dissociation of CIPp-18 from albumin prior to endocytosis. Further, the binding of CIPp-18 on the surface of albumin appears to play a crucial role in disaggregation and cellular uptake of CIPp-18.

Keywords: Albumin binding; Cellular uptake; Disaggregation; Facilitated diffusion; Near-infrared photosensitizer.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

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