Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy
Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is...
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doaj-e7c56eec9f804873b7318ac9c2215ae92021-02-18T00:02:50ZengMDPI AGJournal of Personalized Medicine2075-44262021-02-011113613610.3390/jpm11020136Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic TherapyShanghui Gao0Rayhanul Islam1Jun Fang2Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, JapanFaculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, JapanTargeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent <sup>1</sup>O<sub>2</sub> generation under light irradiation because of micelle formation. However, <sup>1</sup>O<sub>2</sub> was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT.https://www.mdpi.com/2075-4426/11/2/136EPR effecttumor targetingphotodynamichyaluronanzinc protoporphyrin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shanghui Gao Rayhanul Islam Jun Fang |
spellingShingle |
Shanghui Gao Rayhanul Islam Jun Fang Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy Journal of Personalized Medicine EPR effect tumor targeting photodynamic hyaluronan zinc protoporphyrin |
author_facet |
Shanghui Gao Rayhanul Islam Jun Fang |
author_sort |
Shanghui Gao |
title |
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy |
title_short |
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy |
title_full |
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy |
title_fullStr |
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy |
title_full_unstemmed |
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy |
title_sort |
tumor environment-responsive hyaluronan conjugated zinc protoporphyrin for targeted anticancer photodynamic therapy |
publisher |
MDPI AG |
series |
Journal of Personalized Medicine |
issn |
2075-4426 |
publishDate |
2021-02-01 |
description |
Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent <sup>1</sup>O<sub>2</sub> generation under light irradiation because of micelle formation. However, <sup>1</sup>O<sub>2</sub> was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT. |
topic |
EPR effect tumor targeting photodynamic hyaluronan zinc protoporphyrin |
url |
https://www.mdpi.com/2075-4426/11/2/136 |
work_keys_str_mv |
AT shanghuigao tumorenvironmentresponsivehyaluronanconjugatedzincprotoporphyrinfortargetedanticancerphotodynamictherapy AT rayhanulislam tumorenvironmentresponsivehyaluronanconjugatedzincprotoporphyrinfortargetedanticancerphotodynamictherapy AT junfang tumorenvironmentresponsivehyaluronanconjugatedzincprotoporphyrinfortargetedanticancerphotodynamictherapy |
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