Effect of thermal dose on heat shock protein expression after radio-frequency ablation with and without adjuvant nanoparticle chemotherapies

摘要

Purpose: The aim of this study was to evaluate the effect of different radio-frequency ablation (RFA) thermal doses on coagulation and heat shock protein (HSP) response with and without adjuvant nanotherapies. Materials and methods: First, Fischer rats were assigned to nine different thermal doses of hepatic RFA (50–90?°C, 2–20?min, three per group) or no treatment (n?=?3). Next, five of these RF thermal doses were combined with liposomal-doxorubicin (Lipo-Dox, 1?mg intravenously) in R3230 breast tumours, or no tumour treatment (five per group). Finally, RFA/Lipo-Dox was given without and with an Hsp70 inhibitor, micellar quercetin (Mic-Qu, 0.3?mg intravenously) for two different RFA doses with similar coagulation but differing peri-ablational Hsp70 (RFA/Lipo-Dox at 70?°C × 5?min and 90?°C × 2?min, single tumours, five per group). All animals were sacrificed 24?h post-RFA and gross tissue coagulation and Hsp70 (maximum rim thickness and % cell positivity) were correlated to thermal dose including cumulative equivalent minutes at 43?°C (CEMsub43/sub). Results: Incremental increases in thermal dose (CEMsub43/sub) correlated to increasing liver tissue coagulation (Rsup2/sup = 0.7), but not with peri-ablational Hsp70 expression (Rsup2/sup = 0.14). Similarly, increasing thermal dose correlated to increasing R3230 tumour coagulation for RF alone and RFA/Lipo-Dox (Rsup2/sup = 0.7 for both). The addition of Lipo-Dox better correlated to increasing Hsp70 expression compared to RFA alone (RFA: Rsup2/sup = 0.4, RFA/Lipo-Dox: Rsup2/sup = 0.7). Finally, addition of Mic-Qu to two thermal doses combined with Lipo-Dox resulted in greater tumour coagulation (p?p??0.0004). Conclusion: Adjuvant intravenous Lipo-Dox increases peri-ablational Hsp70 expression in a thermally dependent manner. Such expression can be exploited to produce greater tumour destruction when adding a second adjuvant nanodrug (Mic-Qu) to suppress peri-ablational HSP expression.