title: Therapeutic efficacy of novel microwave-sensitized mPEG-PLGA@ZrO2@(DOX + ILS) drug-loaded microspheres in rabbit VX2liver tumours.
abstract: The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO2@(DOX + ILS) (mPEG-PLGA@ZrO2@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO2into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO2@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres in a rabbit VX2liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Mao
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. mengxw@mail.ipc.ac.cn.
authors.forename: Shunsong
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Duo
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Han
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Yutian
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. mengxw@mail.ipc.ac.cn.
authors.forename: Changhui
authors.initials: C
authors.lastname: Fu
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. mengxw@mail.ipc.ac.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. mengxw@mail.ipc.ac.cn.
authors.forename: Xianwei
authors.identifier: http://orcid.org/0000-0002-0350-4760
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China. suhongying67@VIP.163.com.
authors.forename: Hongying
authors.initials: H
authors.lastname: Su
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid; D008113:Liver Neoplasms / Q000188:drug therapy*; D008863:Microspheres; D008872:Microwaves; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011091:Polyesters; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D011817:Rabbits; D015040:Zirconium
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D015040:Zirconium