An acoustic/thermo-responsive hybrid system for advanced doxorubicin delivery in tumor treatment.

Abstract

The efficiency of drug delivery and bioavailability to tumor cells are crucial for effective cancer chemotherapy. Herein, a doxorubicin (DOX) encapsulated lysolipid-based thermosensitive liposome decorated with cRGD peptide (RTSL) is conjugated on the surface of an IR780-loaded microbubble (IMB) to synthesize RTSL-IMBs. Sequentially taking advantage of acoustic-assisted early extravasation and thermo-triggered interstitium ultrafast drug release, RTSL-IMBs combine with ultrasound (US) and laser irradiation can advance drug delivery and bioavailability. In vitro experiments demonstrate that RTSL-IMBs associated with a two-step protocol (subsequently US irradiation for 1 min and laser irradiation for 5 min) can dramatically enhance the cellular uptake and bioavailability of DOX. In vivo fluorescence imaging studies reveal that the combination of RTSL-IMBs and US shows a 2.8-fold intratumoral drug accumulation increase at 0.5 h post-injection, while it will take 48 h to reach the same level of intratumoral drug accumulation for the RTSL-IMB group alone. Interestingly, the following localized application of a laser can further increase drug accumulation and slow tumor clearance. Histological analysis demonstrates that the combinational RTSL-IMBs, US and laser significantly improve the drug penetration distance and delivery efficiency in the tumor core. In this study, the acoustic/thermo-responsive hybrid system shows potential for advancing DOX chemotherapy in breast cancer cell MCF-7 xenograft nude mice.

• Authors: Li Zhang , Shiyu Zhang , Huajian Chen , Yu Liang , Bingxia Zhao , Wanxian Luo , Qian Xiao , Jinheng Li , Junqiao Zhu , Chao Peng , Yaru Zhang , Zhe Hong , Ying Wang , Yingjia Li
• Journal: Biomaterials science (Biomater Sci) Vol. 8 Issue 8 Pg. 2202-2211 (Apr 21 2020) ISSN: 2047-4849 [Electronic] England
• PMID: 32100739 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Liposomes
• Peptides, Cyclic
• cyclic arginine-glycine-aspartic acid peptide
• Doxorubicin

Topics

• Acoustics
• Animals
• Antibiotics, Antineoplastic (administration & dosage, chemistry)
• Doxorubicin (administration & dosage, chemistry)
• Drug Liberation
• Female
• Humans
• Liposomes
• MCF-7 Cells
• Mammary Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Mice, Inbred BALB C
• Mice, Nude
• Microbubbles
• Peptides, Cyclic (administration & dosage, chemistry)
• Temperature
• Tumor Burden (drug effects)
• Ultrasonic Waves
• Xenograft Model Antitumor Assays