| Title | Can two-step ablation combined with chemotherapeutic liposomes achieve better outcome than traditional RF ablation? A solid tumor animal study |
| Authors | Zhao, Kun Wu, Hao Yang, Wei Cheng, Yuxi Wang, Song Jiang, An-na Yan, Kun Goldberg, S. Nahum |
| Affiliation | Peking Univ Canc Hosp & Inst, Dept Ultrasound, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing, Beijing 100142, Peoples R China Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China Hadassah Hebrew Univ Med Ctr, Dept Radiol, Div Image Guided Therapy, Jerusalem, Israel |
| Keywords | COMBINED RADIOFREQUENCY ABLATION DRUG ACCUMULATION IN-VIVO DOXORUBICIN COMBINATION MICROENVIRONMENT HYPERTHERMIA COAGULATION EFFICACY GROWTH |
| Issue Date | Mar-2022 |
| Publisher | NANOSCALE |
| Abstract | Objectives: To determine whether two-step ablation using sequential low and high temperature heating can achieve improved outcomes in animal tumor models when combined with chemotherapeutic liposomes (LP). Materials and methods: Balb/c mice bearing 4T1 tumor received paclitaxel-loaded liposomes followed 24 h later by either traditional RFA (70 degrees C, 5 min) or a low temperature RFA (45 degrees C, 5 min), or two-step RFA (45 degrees C 2 min + 70 degrees C 3 min). Intratumoral drug accumulation and bio-distribution in major organs were evaluated. Periablational drug penetration was evaluated by pathologic staining and the intratumoral interstitial fluid pressure (IFP) was measured directly. For long-term outcomes, mice bearing 4T1 or H22 tumors were randomized into five groups (n = 8 per group): control (no treatment), RFA alone, LP + RFA (45 degrees C), LP + RFA (70 degrees C) and LP + RFA (45 + 70 degrees C). End-point survivals were compared among the different groups. Results: The greater intratumoral drug accumulation (3.35 +/- 0.32 vs. 3.79 +/- 0.29 x 10(8) phot/cm(2)/s at 24 h, p = 0.09), deeper periablational drug penetration (45.7 +/- 5.0 vs. 1.6 +/- 0.5, p < 0.001), and reduced off-target drug deposition in major organs (liver 96.1 +/- 31.6 vs. 47.4 +/- 1.5 x 10(6) phot/cm(2)/s, p < 0.001) were found when combined with RFA (45 degrees C) compared to drug alone. For long-term outcomes, 4T1 tumor growth rates for LP + two-step RFA (45 + 70 degrees C) were significantly slower than those of LP + RFA (70 degrees C), LP + RFA (45 degrees C), and RFA alone (P < 0.01 for all comparisons). End point survival for LP + RFA (45 + 70 degrees C) was also longer than that for LP + RFA (70 degrees C) (median 16 vs. 10 days, p = 0.003) or LP + RFA 45 degrees C (11 days, p = 0.009) and RFA alone (8.3 days, p < 0.001) in 4T1 tumor models. The intratumoral IFP after RFA (45 degrees C) was significantly lower than baseline RFA (3.3 +/- 0.8 vs. 19.2 +/- 3.1 mmHg, p < 0.001), but was not measurable after RFA (70 degrees C). Conclusions: A two-step ablation combined with chemotherapeutic liposomes can achieve better survival benefit compared to traditional RFA in animal models. |
| URI | http://hdl.handle.net/20.500.11897/642077 |
| ISSN | 2040-3364 |
| DOI | 10.1039/d1nr08125j |
| Indexed | EI SCI(E) |
| Appears in Collections: | 北京肿瘤医院 药学院 天然药物与仿生药物国家重点实验室 |
