MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome

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• 作者：Tatsuaki Tagami^a ; Warren D. Foltz^b ; Mark J. Ernsting^a ; Carol M. Lee^c ; Ian F. Tannock^c ; Jonathan P. May^a ; Shyh-Dar Li^a ; ^{sli@oicr.on.ca"" rel=""nofollow}
• 关键词：Thermosensitive liposomes ; Triggered drug release ; Brij ; MRI ; Intratumoral distribution ; Multifunctional nanoparticles
• 刊名：Biomaterials
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：32
• 期：27
• 页码：6570-6578
• 全文大小：1323 K

文摘

Non-invasive in vivo imaging of drug distribution enables real-time monitoring and prediction of therapeutic responses to treatment. We have developed a thermosensitive liposomal formulation (HaT: Hyperthermia-activated-cytoToxic) consisting of DPPC and Brij78, a formulation that enhanced drug delivery compared to the lyso-lipid temperature sensitive liposomes (LTSL). Here we report the development of a multifunctional HaT liposome co-encapsulating Gd-DTPA (an MRI probe) and doxorubicin (DOX), which simultaneously releases and reports on drug delivery in a locally heated tumor. The temperature-dependent release profiles of DOX from HaT were closely related to the change in the MR T₁ relaxation time, in which DOX was 100 % released at 40–42 °C in 3 min, accompanied by a 60 % reduction in T₁. By T₁ relaxometry analysis, no Gd-DTPA leakage was detected in 30 min at 30–37 °C. In the in vivo study, DOX uptake in the tumor was quantitatively correlated with T₁ response (R² = 0.98) and the patterns of the T₁ image and the intratumoral DOX uptake were matched, in which both signals were predominantly detected in the highly perfused tumor periphery. Finally, the extent of T₁ relaxation enhancement in the heated tumor successfully predicted the antitumor efficacy in a standard pharmacological response model (R² = 0.98).