title: ATP/pH Dual Responsive Nanoparticle with d-[des-Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery.
abstract: Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l-form and d-form [des-Arg10]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together. The doxorubicin conjugated polymer is complexed with adenosine-5'-triphosphate (ATP) sensitive hybridized aptamer in self-assembly process by intercalating into the double strand scaffolds. The acid labile conjugating bond and ATP sensitive aptamer endow the nanoparticle with dual responsiveness to intracellular milieu, thus triggering a quick drug release in tumor cells. Remarkable therapeutic effects and tuned in vivo pharmacokinetics profiles are shown by the aptamer complexed drug conjugates nanoparticle with B1R active targeting modification. Therefore the strategies of B1R targeting and ATP/pH dual-responsiveness nanoparticle help achieve enhanced drug accumulation within tumor cells and efficient chemotherapy for breast cancer.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Yu
authors: Y
authors: Zhang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Yifei
authors: Y
authors: Lu
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Feng
authors: F
authors: Wang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Sai
authors: S
authors: An
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Yujie
authors: Y
authors: Zhang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Tao
authors: T
authors: Sun
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Jianhua
authors: J
authors: Zhu
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors: Chen
authors: C
authors: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis; D005260:Female; D006863:Hydrogen-Ion Concentration; D007609:Kallidin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000473:pathology; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D004317:Doxorubicin; D000255:Adenosine Triphosphate
keywords: ATP aptamer intercalation; bradykinin receptor; breast cancer targeting; drug delivery; dual stimuli responsive