Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2020; 10(23):10513-10530. doi:10.7150/thno.49731 This issue Cite

Research Paper

Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy

Xiaoyu Xu*, Binyao Huang*, Zishan Zeng, Jie Chen, Zeqian Huang, Zilin Guan, Meixu Chen, Yanjuan Huang, Chunshun Zhao✉

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, P. R. China.
*These authors contributed equally to this work.

✉ Corresponding author: Chunshun Zhao, E-mail: zhaocssysu.edu.cn.

Citation:
Xu X, Huang B, Zeng Z, Chen J, Huang Z, Guan Z, Chen M, Huang Y, Zhao C. Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy. Theranostics 2020; 10(23):10513-10530. doi:10.7150/thno.49731. https://www.thno.org/v10p10513.htm
Other styles

File import instruction

Abstract

Graphic abstract

Cancer cells immersed in inherent oxidative stress are more vulnerable to exogenous oxidative damages than normal cells. Reactive oxygen species (ROS)-mediated oxidation therapy preferentially aggravating tumor oxidative stress to disrupt redox homeostasis, has emerged as an effective and specific anticancer treatment. Herein, following an ingenious strategy of “broaden sources and reduce expenditure”, we designed a versatile tumor-specific oxidative stress nanoamplifier enabling economized photodynamic therapy (PDT), to achieve synergistic oxidative stress explosion for superior oxidation therapy.

Methods: Cinnamaldehyde (CA) as a therapeutic ROS generator was first conjugated to hyaluronic acid (HA) through acid-labile hydrazone bond to synthesize tailored amphiphilic HA@CA conjugates, which could surprisingly self-assemble into uniform nanofibers in aqueous media. Photosensitizer protoporphyrin (PpIX) was efficiently encapsulated into HA@CA nanofibers and transformed HA@CA nanofibers to final spherical HA@CAP.

Results: With beneficial pH-responsiveness and morphology transformation, improved bioavailability and selective tumor accumulation, HA@CAP combining ROS-based dual chemo/photodynamic treatment modalities could induce cytotoxic ROS generation in a two-pronged approach to amplify tumor oxidative stress, termed “broaden sources”. Moreover, utilizing CA-induced H2O2 production and cascaded Fenton reaction in mitochondria to consume intracellular overloaded Fe(II), HA@CAP could skillfully block endogenic heme biosynthesis pathway on site to restrain undesired elimination of PpIX for economized PDT, termed “reduce expenditure”. Both in vitro and in vivo results demonstrated the superior antitumor performance of HA@CAP.

Conclusion: This study offered an inspiring strategy of “broaden sources and reduce expenditure” to specifically boost tumor oxidative stress for reinforced oxidation therapy.

Keywords: Oxidative stress, oxidation therapy, reactive oxygen species, economized photodynamic therapy, broaden sources and reduce expenditure

Citation styles

APA
Xu, X., Huang, B., Zeng, Z., Chen, J., Huang, Z., Guan, Z., Chen, M., Huang, Y., Zhao, C. (2020). Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy. Theranostics, 10(23), 10513-10530. https://doi.org/10.7150/thno.49731.

ACS
Xu, X.; Huang, B.; Zeng, Z.; Chen, J.; Huang, Z.; Guan, Z.; Chen, M.; Huang, Y.; Zhao, C. Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy. Theranostics 2020, 10 (23), 10513-10530. DOI: 10.7150/thno.49731.

NLM
Xu X, Huang B, Zeng Z, Chen J, Huang Z, Guan Z, Chen M, Huang Y, Zhao C. Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy. Theranostics 2020; 10(23):10513-10530. doi:10.7150/thno.49731. https://www.thno.org/v10p10513.htm

CSE
Xu X, Huang B, Zeng Z, Chen J, Huang Z, Guan Z, Chen M, Huang Y, Zhao C. 2020. Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy. Theranostics. 10(23):10513-10530.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use