Microwave-Triggered Smart Drug Release from Liposomes Co-encapsulating Doxorubicin and Salt for Local Combined Hyperthermia and Chemotherapy of Cancer.

Abstract

The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.

• Authors: Yushen Jin, Xiaolong Liang, Yunkun An, Zhifei Dai
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 27 Issue 12 Pg. 2931-2942 (Dec 21 2016) ISSN: 1520-4812 [Electronic] United States
• PMID: 27998076 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Liposomes
• Sodium Chloride
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• Breast Neoplasms (drug therapy, therapy)
• Doxorubicin (administration & dosage, pharmacokinetics)
• Drug Liberation
• Female
• Hemolysis (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Hyperthermia, Induced (methods)
• Liposomes (administration & dosage, chemistry, pharmacokinetics)
• Mice, Inbred BALB C
• Mice, Nude
• Microwaves
• Sodium Chloride (chemistry)
• Xenograft Model Antitumor Assays