title: Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.
abstract: Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University , Wuhan 430070, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Han
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University , Wuhan 430070, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University , Wuhan 430070, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University , Wuhan 430072, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Wang
authors.affiliation: China Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, China.
authors.forename: Luming
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University , Wuhan 430072, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University , Wuhan 430072, China.
authors.forename: Xianzheng
authors.identifier: 0000-0001-6242-6005
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University , Wuhan 430070, China.
authors.forename: Heyou
authors.identifier: 0000-0001-9406-0722
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008299:Maleic Anhydrides / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D008299:Maleic Anhydrides; D010455:Peptides; D017319:Photosensitizing Agents; C007474:2,3-dimethylmaleic anhydride
keywords: acidity responsive; chimeric peptide; enhanced cellular internalization; geometrical shape switch; photodynamic therapy