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Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers

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Abstract

Albumin nanoparticles have become an attractive cancer nanomedicine platform due to their pharmaceutical advantages. Recently, photothermal therapy has been extensively applied to cancer treatment due to heat-induced tumor ablation. Herein, we fabricated albumin nanoparticles (HSA-NPs) loaded with paclitaxel (PTX), indocyanine green (ICG; a hyperthermal agent) and hyaluronidase (HAase) that breaks down hyaluronan, a major component of the extracellular matrix (ECM) in tumors. Synthesis was based on a slightly modified nanoparticle albumin-bound (Nab™) technique. The prepared nanoparticles (PTX/ICG/HAase-HSA-NPs) had a spherical shape with an average size of ~ 110 nm and a zeta potential of ~ -30.4 mV. They displayed good colloidal stability and typical patterns of ICG, HSA and HAase in UV–VIS–NIR and circular dichroism spectroscopic analysis. PTX/ICG/HAase-HSA-NPs were found to have excellent hyperthermal effects in response to near-infrared laser irradiation (808 nm) (up to > 50 °C over 4 min). The hyperthermia conducted by PTX/ICG/HAase-HSA-NPs resulted in significant cytotoxicity to pancreatic AsPC-1 cells at both severe (> 50 °C) and mild (41–42 °C) hyperthermal states in conjunction with the inherent cytotoxic activity of paclitaxel. Furthermore, the confocal images of AsPC-1 cell spheroids proved PTX/ICG/HAase-HSA-NPs were able to permeate deeply into the three-dimensional tumor tissue mimicry structure. Most of all, PTX/ICG/HAase-HSA-NPs maintained all these physicochemical and anti-cancer properties irrespective of the amount of embedded HAase (1–5 mg). Our results demonstrated that PTX/ICG/HAase-HSA-NPs are a promising hyperthermal/chemotherapeutic anticancer agent.

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Acknowledgements

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (No. NRF-2019R1A5A2027340), and a grant (16173MFDS542) from the Ministry of Food and Drug Safety in 2020.

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Correspondence to Yu Seok Youn.

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Kim, S.S., Kim, H.K., Kim, H. et al. Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers. Arch. Pharm. Res. 44, 182–193 (2021). https://doi.org/10.1007/s12272-020-01264-9

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  • DOI: https://doi.org/10.1007/s12272-020-01264-9

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