Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor
Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hinde...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/137637 |
| _version_ | 1811685998277427200 |
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| author | Phua, Fiona Soo Zeng Yang, Guangbao Lim, Wei Qi Verma, Apoorva Chen, Hongzhong Thanabalu, Thirumaran Zhao, Yanli |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Phua, Fiona Soo Zeng Yang, Guangbao Lim, Wei Qi Verma, Apoorva Chen, Hongzhong Thanabalu, Thirumaran Zhao, Yanli |
| author_sort | Phua, Fiona Soo Zeng |
| collection | NTU |
| description | Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane-modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H2O2) to oxygen, and improving PDT efficacy upon light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and monodispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal microscopy and flow cytometry in the MDA-MB-231 cell line possessing overly expressed CD44 receptors. The encapsulated catalase was able to decompose the endogenous H2O2 to generate O2 in situ for relieving hypoxia in cells incubated under hypoxic conditions. Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic conditions. As a result of the catalase capability in relieving hypoxia, HA-CAT@aCe6 also exhibited high cellular cytotoxicity under hypoxic condition. In vivo experiments revealed selective tumor accumulation of HA-CAT@aCe6 in MDA-MB-231 tumor bearing nude mice. Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase. Thus, HA-CAT@aCe6 demonstrated a great potential in overcoming hypoxia for targeted PDT. |
| first_indexed | 2024-10-01T04:53:25Z |
| format | Journal Article |
| id | ntu-10356/137637 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:53:25Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1376372023-02-28T19:45:59Z Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor Phua, Fiona Soo Zeng Yang, Guangbao Lim, Wei Qi Verma, Apoorva Chen, Hongzhong Thanabalu, Thirumaran Zhao, Yanli School of Physical and Mathematical Sciences Science::Chemistry Nanomedicine Drug Delivery Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane-modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H2O2) to oxygen, and improving PDT efficacy upon light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and monodispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal microscopy and flow cytometry in the MDA-MB-231 cell line possessing overly expressed CD44 receptors. The encapsulated catalase was able to decompose the endogenous H2O2 to generate O2 in situ for relieving hypoxia in cells incubated under hypoxic conditions. Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic conditions. As a result of the catalase capability in relieving hypoxia, HA-CAT@aCe6 also exhibited high cellular cytotoxicity under hypoxic condition. In vivo experiments revealed selective tumor accumulation of HA-CAT@aCe6 in MDA-MB-231 tumor bearing nude mice. Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase. Thus, HA-CAT@aCe6 demonstrated a great potential in overcoming hypoxia for targeted PDT. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version 2020-04-07T04:53:13Z 2020-04-07T04:53:13Z 2019 Journal Article Phua, F. S. Z., Yang, G., Lim, W. Q., Verma, A., Chen, H., Thanabalu, T., & Zhao, Y. (2019). Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor. ACS Nano, 13(4), 4742-4751. doi:10.1021/acsnano.9b01087 1936-0851 https://hdl.handle.net/10356/137637 10.1021/acsnano.9b01087 4 13 4742 4751 en ACS Nano This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsnano.9b01087 application/pdf |
| spellingShingle | Science::Chemistry Nanomedicine Drug Delivery Phua, Fiona Soo Zeng Yang, Guangbao Lim, Wei Qi Verma, Apoorva Chen, Hongzhong Thanabalu, Thirumaran Zhao, Yanli Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title | Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title_full | Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title_fullStr | Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title_full_unstemmed | Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title_short | Catalase-integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| title_sort | catalase integrated hyaluronic acid as nanocarriers for enhanced photodynamic therapy in solid tumor |
| topic | Science::Chemistry Nanomedicine Drug Delivery |
| url | https://hdl.handle.net/10356/137637 |
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