title: Tumor acidity-sensitive linkage-bridged block copolymer for therapeutic siRNA delivery.
abstract: The design of ideal nanoparticle delivery systems should be capable of meeting the requirements of several stages of drug delivery, including prolonged circulation, enhanced accumulation and penetration in the tumor, facilitated cellular internalization and rapid release of the active drug in the tumor cells. However, among the current design strategies, meeting the requirements of one stage often conflicts with the other. Herein, a tumor pH-labile linkage-bridged block copolymer of poly(ethylene glycol) with poly(lacide-co-glycolide) (PEG-Dlinkm-PLGA) was used for siRNA delivery to fulfill all aforementioned requirements of these delivery stages. The obtained siRNA-encapsulating PEG-Dlinkm-PLGA nanoparticle gained efficiently prolonged circulation in the blood and preferential accumulation in tumor sites via the PEGylation. Furthermore, the PEG surface layer was detached in response to the tumor acidic microenvironment to facilitate cellular uptake, and the siRNA was rapidly released within tumor cells due to the hydrophobic PLGA layer. Hence, PEG-Dlinkm-PLGA nanoparticles met the requirements of several stages of drug delivery, and resulted in the enhanced therapeutic effect of the nanoparticular delivery systems.
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Cong-Fei
authors.initials: CF
authors.lastname: Xu
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Hou-Bing
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Sun
authors.affiliation: CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Shen
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei Anhui 230027, PR China. Electronic address: yangxz@mail.ustc.edu.cn.
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei Anhui 230027, PR China; CAS Center for Excellence in Nanoscience, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei Anhui 230027, PR China; Innovation Center for Cell Signaling Network, University of Science and Technology of China, Hefei, Anhui 230027, PR China. Electronic address: jwang699@ustc.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000067492:RNAi Therapeutics; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D003692:Delayed-Action Preparations; D019344:Lactic Acid; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1
keywords: Cancer nanotechnology; PEG detachment; Tumor pH-responsive; siRNA