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

• Published in: Drug delivery Vol. 27; no. 1; pp. 836 - 847
• Main Authors: Du, Chunyang, Li, Shuangshuang, Li, Yuan, Galons, Hervé, Guo, Na, Teng, Yuou, Zhang, Yongmin, Li, Mingyuan, Yu, Peng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2020; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Apoptosis; Biological Availability; Cancer therapies; Cell division; Cell Line, Tumor; Chemotherapy; co-delivery; Cooperation; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; Drug delivery systems; Drug Delivery Systems - methods; Drug dosages; Drug resistance; Fever; Humans; Hydrogen-Ion Concentration; Hyperthermia; Kinases; Liposomes - chemistry; Liposomes - pharmacokinetics; Lung cancer; Mice; Nanoparticles; Nanostructures; Nutrition; Permeability; Pharmaceutical sciences; Physiology; thermosensitive liposome; Tissue Distribution - drug effects; Topoisomerase I Inhibitors - chemistry; Topoisomerase I Inhibitors - pharmacokinetics; topotecan; Topotecan - chemistry; Topotecan - pharmacokinetics; Transition Temperature; tumor hyperthermia; Tumors; Xenograft Model Antitumor Assays; co-delivery; F7; tumor hyperthermia; thermosensitive liposome; topotecan
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2020.1772409

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.