F7 and topotecan co-loaded thermosensitive liposome as a nano-drug delivery system for tumor hyperthermia

Chunyang Du; Shuangshuang Li; Yuan Li; Hervé Galons; Na Guo; Yuou Teng; Yongmin Zhang; Mingyuan Li; Peng Yu

doi:10.1080/10717544.2020.1772409

F7 and topotecan co-loaded thermosensitive liposome as a nano-drug delivery system for tumor hyperthermia

Drug Deliv. 2020 Dec;27(1):836-847. doi: 10.1080/10717544.2020.1772409.

Authors

Chunyang Du¹, Shuangshuang Li¹, Yuan Li¹, Hervé Galons^{1

2}, Na Guo¹, Yuou Teng¹, Yongmin Zhang^{1

2}, Mingyuan Li¹, Peng Yu¹

Affiliations

¹ College of Biotechnology, China International Science and Technology, Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin International Cooperation Research Centre of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science & Technology/Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin, China.
² Institut Parisien de Chimie Moléculaire, UMR CNRS 8232, Paris, France.

Abstract

In order to enhance the targeting efficiency and reduce anti-tumor drug's side effects, topotecan (TPT) and F7 were co-loaded in thermosensitive liposomes (F7-TPT-TSL), which show enhanced permeability and retention in tumors, as well as local controlled release by heating in vitro. TPT is a water-soluble inhibitor of topoisomerase I that is converted to an inactive carboxylate structure under physiological conditions (pH 7.4). F7 is a novel drug significantly resistant to cyclin-dependent kinase but its use was restricted by its high toxicity. F7-TPT-TSL had excellent particle distribution (about 103 nm), high entrapment efficiency (>95%), obvious thermosensitive property, and good stability. Confocal microscopy demonstrated specific higher accumulation of TSL in tumor cells. MTT proved F7-TPT-TSL/H had strongest cell lethality compared with other formulations. Then therapeutic efficacy revealed synergism of TPT and F7 co-loaded in TSL, together with hyperthermia. Therefore, the F7-TPT-TSL may serve as a promising system for temperature triggered cancer treatment.

Keywords: F7; co-delivery; thermosensitive liposome; topotecan; tumor hyperthermia.

MeSH terms

Animals
Antibiotics, Antineoplastic / chemistry
Antibiotics, Antineoplastic / pharmacokinetics
Biological Availability
Cell Line, Tumor
Drug Delivery Systems / methods*
Humans
Hydrogen-Ion Concentration
Hyperthermia
Liposomes* / chemistry
Liposomes* / pharmacokinetics
Mice
Nanostructures
Tissue Distribution / drug effects
Topoisomerase I Inhibitors / chemistry
Topoisomerase I Inhibitors / pharmacokinetics
Topotecan* / chemistry
Topotecan* / pharmacokinetics
Transition Temperature
Xenograft Model Antitumor Assays

Substances

Antibiotics, Antineoplastic
Liposomes
Topoisomerase I Inhibitors
Topotecan

Grants and funding

The research was supported by Tianjin Natural Science General Project Fund [2018KJ124] and Open Fund of Tianjin Enterprise Key Laboratory on Hyaluronic Acid Application Research [no. KTRDHA-Y201906] provided by Tianjin Kangting Bioengineering Group Corp. Ltd.