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

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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.

Graphical abstract: An acoustic/thermo-responsive hybrid system for advanced doxorubicin delivery in tumor treatment

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Supplementary files

Article information


Submitted
05 Nov 2019
Accepted
31 Jan 2020
First published
26 Feb 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

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

L. Zhang, S. Zhang, H. Chen, Y. Liang, B. Zhao, W. Luo, Q. Xiao, J. Li, J. Zhu, C. Peng, Y. Zhang, Z. Hong, Y. Wang and Y. Li, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/C9BM01794A

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