title: Tat/HA2 Peptides Conjugated AuNR@pNIPAAm as a Photosensitizer Carrier for Near Infrared Triggered Photodynamic Therapy.
abstract: To achieve an efficiency of intracellular photosensitizers (PSs) delivery and efficacy of photodynamic therapy, we have developed a novel class of PS formulation for encapsulating sulfonated aluminum phthalocyanine (AlPcS4) by taking advantage of the membrane-disruptive peptides Tat/HA2 and the photothermally triggered delivery system using AuNR@pNIPAAm. The coordinated effects of cell penetrating peptide Tat and fusogenic peptide HA2 could enhance the efficient cellular internalization and endo/lysosome escape of PSs delivery systems. Singlet oxygen generation was inhibited due to the reaction between loaded AlPcS4 and Au nanorods, which indicated that the AlPcS4-loaded, AuNR@pNIPAAm delivery system might be nonphototoxic in the circulatory system. However, this PSs-loaded nanosystem became highly phototoxic as it underwent the near-infrared irradiation by using the combined lights of 808 and 680 nm. Upon irradiation, the Tat/HA2 conjugated AuNR@pNIPAAm-Pc elicited an active photodynamic response against the cancer cells, leading to effective cells killing via mitochondria-associated apoptotic pathway. This study also demonstrated improved PDT therapeutic efficacy after intravenous administration of Tat/HA2-AuNR@pNIPAAm-Pc and the subsequent lights irradiations in tumor-bearing mice. We describe here a strategy for enhanced photodynamic eradication of solid tumors by endo/lysosomal escape and highlight the great promise of peptide-based nanocarriers used for cancer therapy.
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Shefang
authors.initials: S
authors.lastname: Ye
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Caiding
authors.initials: C
authors.lastname: Wang
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Yarun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.affiliation: †Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, ‡Medical College, and §State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry*; D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D011992:Endosomes / Q000187:drug effects; D005260:Female; D015696:Gene Products, tat / Q000008:administration & dosage / Q000737:chemistry*; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007259:Infrared Rays; D008247:Lysosomes / Q000187:drug effects; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D015696:Gene Products, tat; D010455:Peptides; D017319:Photosensitizing Agents; C052970:poly-N-isopropylacrylamide; D006046:Gold
keywords: Tat/HA2 peptide; endo/lysosome escape; gold nanorods; photodynamic therapy