Research Article

Preparation and evaluation of paclitaxel-loaded reactive oxygen species and glutathione redox-responsive poly(lactic-co-glycolic acid) nanoparticles for controlled release in tumor cells

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

‡These authors contributed equally to this work

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Feng Han^‡

https://orcid.org/0000-0001-6836-2399

College of Grassland Resources & Environment, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, 010000, People's Republic of China

Key Laboratory of Grassland Resources, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, Ministry of Education, 010000, People's Republic of China

‡These authors contributed equally to this work

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Lanlan Xie

https://orcid.org/0000-0002-8815-4164

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

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Yanjie Liu

https://orcid.org/0000-0002-7003-2134

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

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Qilei Yang

https://orcid.org/0000-0002-6471-5242

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

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Dongmei Zhao

*Author for correspondence: Tel.: +86 451 8219 1517;

E-mail Address: 156828568@qq.com

https://orcid.org/0000-0002-6426-5839

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

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Xiuhua Zhao

**Author for correspondence:

E-mail Address: xiuhuazhao@nefu.edu.cn

https://orcid.org/0000-0003-4602-1934

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

College of Chemistry, Chemical Engineering & Resource Utilization, Northeast Forestry University, Harbin, 150040, People's Republic of China

Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, People's Republic of China

Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-based Active Substances, Harbin 150040, People's Republic of China

College of Grassland Resources & Environment, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, 010000, People's Republic of China

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Published Online:13 Jan 2023

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Abstract

Aim: To formulate and assess the anticancer effect of the poly(lactic-co-glycolic acid) (PLGA) copolymer with the thioether groups (diethyl sulfide [Des]) and disulfide bond (cystamine containing disulfide [Cys]), which encapsulated the anticancer drug paclitaxel (PTX) and triggered PTX release in cancer cell H₂O₂-rich or glutathione-rich surroundings. Methods: PLGA-b-P (Des@Cys) and PLGA-b-P nanoparticles loaded with PTX were prepared and characterized in vitro. The delivery ability of the PLGA-b-P nanoparticles and PLGA-b-P-PTX nanoparticles was assessed on a CT26 (mouse colon cancer cell line) and mouse lung cancer LLC model. Results: The nanoparticles were successfully prepared. Compared with free PTX, the formulated PLGA-b-P nanoparticles loaded with PTX exhibited greater accumulation at the tumor site in the mouse model. Conclusion: PLGA-b-P nanoparticles promote drug accumulation at tumor sites, providing an effective strategy for an intelligent, responsive drug-delivery system.

Plain language summary

Cancer is one of the diseases with the highest mortality rate in the world. Chemotherapy is the most frequently used method of cancer treatment. However, traditional chemotherapeutic drugs have the disadvantages of lack of specificity, high toxicity to the human body, lack of tumor targeting, inability to exist stably in the body, ease of clearance by the body and drug resistance to tumors, so clinical application is limited. Paclitaxel is widely used in the treatment of various cancers, and its use is limited due to the above disadvantages. The purpose of this study was to construct a nanodelivery system with dual responses to the tumor microenvironment, enabling the efficient accumulation of paclitaxel in solid tumors through the enhanced permeability and retention effect, enhancing the therapeutic effect of cancer. This study also investigated the intravenous safety of this dual-responsive nanodelivery system. It evaluated the toxic effects of drug-loaded nanoparticles on cancer cells and validated the controlled release of nanoparticles at tumor sites by in vivo imaging in mice. The authors concluded that tumor microenvironment dual-responsive nanoparticles are a novel and promising nanodelivery system as an intelligently responsive anticancer agent with great promise in future clinical trials.

Tweetable abstract

This study prepared polymer nanocarriers (PLGA-b-p-NPs) with double response to the tumor microenvironment and loaded with traditional antitumor drug paclitaxel, so that drugs can accurately reach tumor cells and be rapidly released in cells.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 17, No. 22

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Received 29 June 2022

Accepted 28 November 2022

Published online 13 January 2023

Published in print September 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2022-0164

Author contributions

S Wang: investigation, methodology, data curation, formal analysis, writing – original draft, writing – review and editing; F Han: investigation, methodology, validation, visualization; L Xie: investigation, formal analysis, methodology, validation; Y Liu: methodology, validation; Q Yang: methodology, validation; D Zhao and X Zhao: investigation, methodology, validation, visualization. All authors contributed to the writing of the paper.

Financial & competing interests disclosure

The authors are grateful for the precious comments and careful corrections made by anonymous reviewers. The authors would also like to acknowledge financial support from “the Fundamental Research Funds for the Central Universities” 2572016CA12, Heilongjiang Touyan Innovation Team Program (Tree Genetics and Breeding Innovation Team), the 111 Project (B20088) and the Fundamental Research Funds for the Central Universities (2572020AW23), Inner Mongolia Natural Science Foundation–Doctoral Foundation Project (2021BS03037). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Administration Committee of Experimental Animals, Heilongjiang Province, China. All of the experimental procedures involving animals were conducted in accordance with the Institutional Animal Care guidelines of Harbin Medical University, China, and approved by the Administration Committee of Experimental Animals, Heilongjiang Province, China.

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