Immunostimulatory cytokine and doxorubicin co-loaded nanovesicles for cancer immunochemotherapy

Tingting Wu; Qi Qiao; Xianya Qin; Dan Zhang; Zhiping Zhang

doi:10.1016/j.nano.2019.02.008

Immunostimulatory cytokine and doxorubicin co-loaded nanovesicles for cancer immunochemotherapy

Nanomedicine. 2019 Jun:18:66-77. doi: 10.1016/j.nano.2019.02.008. Epub 2019 Mar 2.

Authors

Tingting Wu¹, Qi Qiao², Xianya Qin², Dan Zhang², Zhiping Zhang³

Affiliations

¹ Department of Pharmacy, Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China; Tongji School of Pharmacy, HuaZhong University of Science and Technology, Wuhan, China; National Engineering Research Center for Nanomedicine, HuaZhong University of Science and Technology, Wuhan, China; Hubei Engineering Research Center for Novel Drug Delivery System, HuaZhong University of Science and Technology, Wuhan, China.
² Tongji School of Pharmacy, HuaZhong University of Science and Technology, Wuhan, China; National Engineering Research Center for Nanomedicine, HuaZhong University of Science and Technology, Wuhan, China; Hubei Engineering Research Center for Novel Drug Delivery System, HuaZhong University of Science and Technology, Wuhan, China.
³ Tongji School of Pharmacy, HuaZhong University of Science and Technology, Wuhan, China; National Engineering Research Center for Nanomedicine, HuaZhong University of Science and Technology, Wuhan, China; Hubei Engineering Research Center for Novel Drug Delivery System, HuaZhong University of Science and Technology, Wuhan, China. Electronic address: zhipingzhang@mail.hust.edu.cn.

PMID: 30831276
DOI: 10.1016/j.nano.2019.02.008

Abstract

Taking advantages of drug delivery system, immunostimulatory and chemotherapeutic agents with different physiochemical properties can be co-delivered to realize synergistic antitumor effect. Here the immunostimulatory cytokine interleukin-2 (IL-2) was firstly adsorbed in doxorubicin (DOX) loaded nanovesicles (NV-DOX_IL-2) with high encapsulation efficiency by a facile solvent free method. After intravenous injection to melanoma bearing mice, NV-DOX_IL-2 can accumulate in tumor and remarkably suppress tumor growth with negligible systemic toxicity. To extend the comprehensive application of this strategy, interferon-γ (IFN-γ) was further introduced to the combinatorial system to develop cytokine cocktails adsorbed NVs. This kind of NVs can significantly inhibit the primary tumor growth and lung metastasis of triple-negative breast cancer. With exploration of underlying mechanism, the cytokine cocktails adsorbed NVs can facilitate maturation of dendritic cells, promote the infiltration and activation of CD8⁺ T lymphocytes and natural killer cells, and increase the recruitment of CD45⁺ immune cells and Ly6G⁺ neutrophils.

Keywords: Cancer; Combinational therapy; Cytokine; Immunochemotherapy; Nanovesicles.

Publication types

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

MeSH terms

Animals
Cell Line, Tumor
Cytokines / pharmacology
Cytokines / therapeutic use*
Doxorubicin / pharmacology
Doxorubicin / therapeutic use*
Drug Compounding
Immunotherapy*
Interferon-gamma / pharmacology
Interferon-gamma / therapeutic use
Interleukin-2 / pharmacology
Interleukin-2 / therapeutic use
Lung Neoplasms / secondary
Mice
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Neoplasms / drug therapy
Neoplasms / immunology*
Neoplasms / therapy*

Substances

Cytokines
Interleukin-2
Doxorubicin
Interferon-gamma