Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 14, Issue 8D, Pages 1384-1395Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2018.2594
Keywords
Liposome-Microbubble Complexes; Ultrasound; iRGD; Drug Delivery; Breast Tumor
Funding
- National Key Basic Research Program of China (973 Program) [2014CB744502]
- National Natural Science Foundation of China [81371563, 81360482, 81571701, 11534013, 11325420, 81471768, 81527901]
- Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province [2014B030301013]
- Natural Science Foundation of Guangdong Province [2017A030313651, 2014A030313341, 2016A020213004]
- Shenzhen Science and Technology Innovation Committee [JCYJ20150521144321010, JCYJ20170413100222613, JCYJ20170307165254568]
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Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered local drug release. However, it is still desirable for the released drugs to be delivered to tumors as effectively as possible. Here, we fabricated iRGD-targeted paclitaxel-loaded liposome-microbubble complexes (iRGD-PTX-LMC) and investigated the feasibility of enhancing the local drug delivery to breast tumors by using these complexes along with ultrasound irradiation. Our results showed that iRGD-modified PTX-loaded liposomes (iRGD-PTX-PL) were successfully conjugated to the surface of microbubbles (MBs) through biotin-avidin linkage. The resulting iRGD-PTX-LMC retained the ultrasound imaging capability and showed effective ultrasound-triggered drug release. High cell affinity and enhanced drug delivery into tumor cells was confirmed for iRGD-PTX-LMC upon ultrasound exposure. Additionally, our data revealed that iRGD-PTX-LMC with ultrasound had a significantly better tumor growth inhibition effect than iRGD-PTX-PL or nontargeted PTX-LMC in not only in vitro but also in vivo studies. Histological examination indicated that the inhibition of tumor growth was caused by the increases in the drug concentration and the number of apoptotic tumor cells in tumor xenografts. In conclusion, our study revealed the great potential of iRGD-PTX-LMC as a new tool to enhance local drug delivery and significantly improve antitumor efficacy.
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