PMID- 29758547 OWN - NLM STAT- MEDLINE DCOM- 20190813 LR - 20190813 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 173 DP - 2018 Aug TI - Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer. PG - 58-70 LID - S0142-9612(18)30326-0 [pii] LID - 10.1016/j.biomaterials.2018.04.054 [doi] AB - To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C(3)F(8). Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for PDT, while amino groups could adsorb siRNA through electrostatic interaction for FOXA1 KD, which could inhibit the proliferation of estrogen-dependent ER+ BC. This system showed high photosensitizer and gene loading content. Moreover, CpMBs/siRNA can be converted into nanoparticles with low-frequency pulsed ultrasound (LFUS) exposure, which increase the transfection efficiency of siRNA ( approximately 4 fold) and the porphyrin uptake ( approximately 8 fold) in MCF-7 (a human breast cancer cell line, ER+) by sonoporation effect. In vivo, UTMD was performed under the guidance of CEUS, and the fluorescence intensity of CpMBs/siRNA at the tumour site reached a peak value at 6 h after injection and it was retained in the following 24 h. Furthermore, there was no tumour recurrence during the observation period (21 days) in the group of PDT combined with FXOA1 KD. Compared to the PDT or FOXA1 KD alone group, the combination of these two methods was much more efficient in inhibiting ER+ breast cancer, showing a good synergistic effect. CpMBs/siRNA combined with UTMD dramatically increased the local accumulation of porphyrin and siRNA through ultrasound-induced sonoporation effect under the guidance of CEUS, showing excellent therapeutic effect for estrogen-dependent ER+ breast cancer. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Zhao, Ranran AU - Zhao R AD - Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China; Ordos Center Hospital, Ordos, Inner Mongolia 017000, China. FAU - Liang, Xiaolong AU - Liang X AD - Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China. FAU - Zhao, Bo AU - Zhao B AD - Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China. FAU - Chen, Min AU - Chen M AD - Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 10019, China. FAU - Liu, Renfa AU - Liu R AD - Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 10019, China. FAU - Sun, Sujuan AU - Sun S AD - Ordos Center Hospital, Ordos, Inner Mongolia 017000, China. FAU - Yue, Xiuli AU - Yue X AD - School of Environment, Harbin Institute of Technology, Harbin 150080, China. Electronic address: xiulidx@163.com. FAU - Wang, Shumin AU - Wang S AD - Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China; Ordos Center Hospital, Ordos, Inner Mongolia 017000, China. Electronic address: shuminwang2014@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180503 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (FOXA1 protein, human) RN - 0 (Hepatocyte Nuclear Factor 3-alpha) RN - 0 (Lipids) RN - 0 (Photosensitizing Agents) RN - 0 (Porphyrins) RN - 0 (RNA, Small Interfering) RN - U6F3787206 (Aminocaproic Acid) MH - Aminocaproic Acid/chemistry MH - Animals MH - Apoptosis MH - Breast Neoplasms/*therapy MH - Combined Modality Therapy MH - Female MH - Genetic Therapy/*methods MH - Hepatocyte Nuclear Factor 3-alpha/*genetics MH - Heterografts MH - Humans MH - Lipids/chemistry MH - MCF-7 Cells MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microbubbles MH - Nanoparticles/chemistry MH - Photochemotherapy/*methods MH - Photosensitizing Agents/chemistry MH - Porphyrins/*chemistry MH - RNA, Small Interfering/*chemistry/genetics MH - Static Electricity MH - *Ultrasonic Waves OTO - NOTNLM OT - Breast cancer OT - Cationic porphyrin OT - Photodynamic therapy OT - RNA interference OT - Ultrasound EDAT- 2018/05/15 06:00 MHDA- 2019/08/14 06:00 CRDT- 2018/05/15 06:00 PHST- 2018/01/16 00:00 [received] PHST- 2018/04/29 00:00 [revised] PHST- 2018/04/30 00:00 [accepted] PHST- 2018/05/15 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2018/05/15 06:00 [entrez] AID - S0142-9612(18)30326-0 [pii] AID - 10.1016/j.biomaterials.2018.04.054 [doi] PST - ppublish SO - Biomaterials. 2018 Aug;173:58-70. doi: 10.1016/j.biomaterials.2018.04.054. Epub 2018 May 3.