title: Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.
abstract: Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation.
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China; Ultrasound Research and Education Institute, Tongji University School of Medicine, 301 Yan-hang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China; Ultrasound Research and Education Institute, Tongji University School of Medicine, 301 Yan-hang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China; Ultrasound Research and Education Institute, Tongji University School of Medicine, 301 Yan-hang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Xiaowan
authors.initials: X
authors.lastname: Bo
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai, 200050, PR China. Electronic address: hrchen@mail.sic.ac.cn.
authors.forename: Hangrong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan-chang-zhong Road, Shanghai, 200072, PR China; Ultrasound Research and Education Institute, Tongji University School of Medicine, 301 Yan-hang-zhong Road, Shanghai, 200072, PR China. Electronic address: xuhuixiong@l26.com.
authors.forename: Huixiong
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002166:Camptothecin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008610:Menthol / Q000494:pharmacology / Q000627:therapeutic use; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry*; D010539:Permeability; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061208:Pulsed Radiofrequency Treatment; D051381:Rats; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D009842:Oligopeptides; D008610:Menthol; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C047981:arginyl-glycyl-aspartic acid; D002166:Camptothecin
keywords: Chemotherapy; RF ablation; RF-responsive drug delivery; RGD active targeting; Radiofrequency (RF)-enhanced permeability; Synergistic retention