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F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma

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Abstract

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666 nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

Mr. Milan Paul acknowledges the Indian Council of Medical Research (ICMR) for providing a senior research fellowship. The authors are extremely grateful to the Central Analytical Laboratory at the Birla Institute of Technology and Science (BITS), Pilani, Hyderabad Campus, India, for providing the instrumentation facilities such as XRD, DSC, FACS, and SEM for various characterizations.

Funding

The work was funded by the Indian Council of Medical Research, Government of India, to Swati Biswas through grant number 2021/8945.

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Authors and Affiliations

  1. Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad, 500078, Telangana, India

    Milan Paul, Balaram Ghosh & Swati Biswas

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  1. Milan Paul
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  2. Balaram Ghosh
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  3. Swati Biswas
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Contributions

Milan Paul: Methodology, Validation, Investigation, Data curation, Writing-Original draft preparation, Editing. Balaram Ghosh: Conceptualization, Validation, Writing- Reviewing and Editing, Supervision. Swati Biswas: Conceptualization, Validation, Writing- Reviewing and Editing, Supervision.

Corresponding author

Correspondence to Swati Biswas.

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Ethics approval and consent to participate

In vivo experiments adhered to CPCSEA guidelines (BITS-Hyd/IAEC/2023/36) approved by IAEC, Department of Pharmacy, BITS Pilani, Hyderabad.

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The authors declare that all authors have been actively involved in the work leading to this paper, and all take responsibility for the published work.

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The authors declare no competing interests.

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Paul, M., Ghosh, B. & Biswas, S. F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01619-5

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