Controllable release of nitric oxide and doxorubicin from engineered nanospheres for synergistic tumor therapy

Lianjiang Tan; Ran Huang; Xiaoqiang Li; Shuiping Liu; Yu-Mei Shen

doi:10.1016/j.actbio.2017.05.019

Controllable release of nitric oxide and doxorubicin from engineered nanospheres for synergistic tumor therapy

Acta Biomater. 2017 Jul 15:57:498-510. doi: 10.1016/j.actbio.2017.05.019. Epub 2017 May 9.

Authors

Lianjiang Tan¹, Ran Huang², Xiaoqiang Li³, Shuiping Liu³, Yu-Mei Shen⁴

Affiliations

¹ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: ljtan@sjtu.edu.cn.
² State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
³ Key Laboratory of Eco-Textiles, Ministry of Education and College of Textile & Clothing, Jiangnan University, Wuxi 214122, China.
⁴ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: yumeishen@sjtu.edu.cn.

PMID: 28499633
DOI: 10.1016/j.actbio.2017.05.019

Abstract

NaYF₄:Yb,Er upconversion nanoparticles (UCNPs) capped with long-chain carboxylic acid were synthesized and then conjugated with chitosan (CS) in the aid of N-hydroxysuccinimide. The resultant nanocompound was integrated with doxorubicin (DOX) and Roussin's black salt (RBS), a photosensitive nitric oxide (NO) donor to produce stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres as nanocarriers for controllable drug delivery. On the one hand, the encapsulated UCNPs can efficiently absorb NIR photons and convert them into visible photons to trigger NO release. On the other hand, the entrapped DOX can be released at lowered pH from the swollen nanospheres caused by stretched oleoyl-CS chains under acidic conditions. The UCNPs(DOX)@CS-RBS nanospheres exhibit great therapeutic efficacy, which is attributable to the combination of NO and DOX releases based on NO dose-dependent mechanisms. This study highlights the controllable release of NO and DOX from the same nanocarriers and the synergistic therapeutic effect on tumors, which could give new insights into improving cancer nanotherapeutics.

Statement of significance: In this paper, core-shell structured UCNPs(DOX)@CS-RBS nanospheres have been designed and synthesized via a step-by-step procedure. The stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres act as nanocarriers for controllable drug delivery towards cancer therapy. The encapsulated UCNPs can efficiently absorb NIR photons and convert them into visible light to trigger NO release. Meanwhile, the entrapped DOX can be released from the swollen nanospheres caused by stretched oleoyl-CS chains at lowered pH typical of intracellular environment. Synergistic cancer therapy will be achieved through the combination of NO and DOX releases based on NO dose-dependent mechanisms. This study provides new drug nanocarriers with high antitumor efficacy for synergistic cancer therapy.

Keywords: Antitumor; Controllable release; Doxorubicin; Nitric oxide; Synergistic therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Delayed-Action Preparations / chemistry
Delayed-Action Preparations / pharmacokinetics
Delayed-Action Preparations / pharmacology
Doxorubicin* / chemistry
Doxorubicin* / pharmacokinetics
Doxorubicin* / pharmacology
Female
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Nanospheres* / chemistry
Nanospheres* / therapeutic use
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Nitric Oxide* / chemistry
Nitric Oxide* / pharmacokinetics
Nitric Oxide* / pharmacology

Substances

Delayed-Action Preparations
Nitric Oxide
Doxorubicin