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Anti-cancer liposomal chemophototherapy using bilayer-localized photosensitizer and cabazitaxel

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Abstract

Photodynamic therapy (PDT) is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent chemotherapy. Previously, we demonstrated that liposomes containing a bilayer-anchored photosensitizer (porphyrin-phospholipid; PoP) can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with red-light. In the present work, we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of liposomes. Cabazitaxel (CTX) is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar% PoP, generating CTX-loaded PoP liposomes (CTX-PoP-Lip). CTX-PoP-Lip showed unilamellar vesicle morphology, and exhibited integrity in storage and serum, while maintaining drug stability under laser irradiation. In vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip, compared to control treatments. In vivo pharmacokinetic analysis revealed that following intravenous administration to mice, CTX and PoP exhibited somewhat altered circulation profiles, suggesting that the CTX may have exchanged with serum factors in blood. Nevertheless, when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors, tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were ineffective. These results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.

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Acknowledgements

This study was supported by the National Institutes of Health (No. R01EB017270) and The National Natural Science Foundation of China (No. 82001752). The authors thank Dandan Luo for discussion and Donna M. Ruszaj for assistance with LC-MS measurements.

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Authors and Affiliations

  1. Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China

    Boyang Sun, Meiling Tian & Shuai Shao

  2. Department of Biomedical Engineering, University at Buffalo State University of New York, Buffalo, NY, 14260, USA

    Boyang Sun, Sanjana Ghosh, Xuedan He, Wei-Chiao Huang, Breandan Quinn, Moustafa T. Mabrouk & Jonathan F. Lovell

  3. Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A0C7, Canada

    Dushyant Jahagirdar & Joaquin Ortega

  4. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300000, China

    Yumiao Zhang

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  1. Boyang Sun
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Correspondence to Yumiao Zhang, Shuai Shao or Jonathan F. Lovell.

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JFL and W.-C.H. hold interest in POP Biotechnologies. Other authors declare no conflict.

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Sun, B., Ghosh, S., He, X. et al. Anti-cancer liposomal chemophototherapy using bilayer-localized photosensitizer and cabazitaxel. Nano Res. 15, 4302–4309 (2022). https://doi.org/10.1007/s12274-022-4090-3

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