Pulsed-wave Ultrasound Hyperthermia Enhanced Nanodrug Delivery Combined with Chloroquine Exerts Effective Antitumor Response and Postpones Recurrence
- Resource Type
- Authors
- Chih-Chun Liu; Yu-Hone Hsu; Chi-Feng Chiang; Shi-Chuen Miaw; Po-Chin Liang; Win-Li Lin
- Source
- Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
Scientific Reports
- Subject
- Cancer microenvironment
0301 basic medicine
Hyperthermia
medicine.medical_treatment
lcsh:Medicine
Pharmacology
Article
Mice
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
Chloroquine
Cell Line, Tumor
Chemotherapy
Animals
Medicine
Doxorubicin
lcsh:Science
Mice, Inbred BALB C
Multidisciplinary
business.industry
Autophagy
lcsh:R
Mammary Neoplasms, Experimental
Cancer
Hyperthermia, Induced
medicine.disease
Cancer metabolism
Blot
030104 developmental biology
Ultrasonic Waves
Cancer cell
Nanoparticles
Female
lipids (amino acids, peptides, and proteins)
lcsh:Q
business
Adjuvant
030217 neurology & neurosurgery
medicine.drug
- Language
- English
- ISSN
- 2045-2322
Autophagy is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. In this study, we investigated the anti-tumor effect of combining pulsed-wave ultrasound hyperthermia (pUH) enhanced PEGylated liposomal doxorubicin (PLD) delivery with an autophagy inhibitor chloroquine (CQ). BALB/c mice bearing subcutaneous 4T1 tumor received intravenous injection of PLD (10 mg/kg) plus 15-minute on-tumor pUH on Day 5 after tumor implantation and were then fed with CQ (50 mg/kg daily) thereafter. Prolonged suppression of tumor growth was attained with PLD + pUH + CQ treatment, whereas in PLD + pUH group tumors quickly recurred after an initial inhibition. Treatment with CQ monotherapy had no benefit compared to the control group. Immunohistochemical staining and Western blotting showed that autophagy of cancer cells was blocked for the mice receiving CQ. It indicates that PLD + pUH + CQ is a promising strategy to treat cancer for a long-term inhibition.