An acoustic/thermo-responsive hybrid system for advanced doxorubicin delivery in tumor treatment
Li Zhang, Shiyu Zhang, Huajian Chen, Liang Yu, Bingxia Zhao, Wanxian Luo, Qian Xiao, Jin‐Heng Li, Junqiao Zhu, Chao Peng, Yaru Zhang, Hong Zhe, Ying Wang, Yingjia Li
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.