期刊
MOLECULAR PHARMACEUTICS
卷 18, 期 9, 页码 3342-3351出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.1c00263
关键词
liposome; doxorubicin; neovasculature; stimuli-sensitive; MRI
资金
- Ministry of Education, Science, Sports, and Culture in Japan [26242049]
- Department of Science and Technology-Japan Society for the Promotion of Science [DST/INT/JSPS/P-221/2016]
- Japan Agency for Medical Research and Development [16cm0106202h]
- Kakenhi [17H00860]
- Center of Innovation Program of the Japan Science and Technology Agency [JPMJCE1305]
- Grants-in-Aid for Scientific Research [17H00860, 26242049] Funding Source: KAKEN
This study aims to enhance the therapeutic effect of liposomes by accumulating doxorubicin-loaded liposomes at high concentrations in and around the tumor, followed by heat trigger drug release to facilitate low-molecular-weight drug penetration throughout the tumor. The targeted thermosensitive liposomes successfully inhibited tumor growth and achieved tumor remission through multiple administrations and heat treatments. Combining tumor neovascular targeting and heat-triggered drug release, these liposomes offer high potential for minimally invasive and effective cancer chemotherapy.
Poor distribution of nanocarriers at the tumor site and insufficient drug penetration into the tissue are major challenges in the development of effective and safe cancer therapy. Here, we aim to enhance the therapeutic effect of liposomes by accumulating doxorubicin-loaded liposomes at high concentrations in and around the tumor, followed by heat-triggered drug release to facilitate low-molecular-weight drug penetration throughout the tumor. A cyclic RGD peptide (cRGD) was incorporated into liposomes decorated with a thermosensitive polymer that allowed precise tuning of drug release temperature (i.e., Polymer-lip) to develop a targeted thermosensitive liposome (cRGD-Polymer-lip). Compared with conventional thermosensitive liposomes, cRGDPolymer-lip enhanced the binding of liposomes to endothelial cells, leading to their accumulation at the tumor site upon intravenous administration in tumor-bearing mice. Drug release triggered by local heating strongly inhibited tumor growth. Notably, tumor remission was achieved via multiple administrations of cRGD-Polymer-lip and heat treatments. Thus, combining the advantages of tumor neovascular targeting and heat-triggered drug release, these liposomes offer high potential for minimally invasive and effective cancer chemotherapy.
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