title: Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery.
abstract: In this study, the amphiphilic fluorinated peptide dendrons functionalized dextran (FPD-HZN-Dex) via an acid-sensitive hydrazone linkage was successfully designed and prepared for the first time. We demonstrated a spontaneous self-assembly of amphiphilic FPD-HZN-Dex into the well-defined nanoparticles with the core-shell architecture in aqueous media, which is attributed to the efficient amphiphilic functionalization of dextran by the hydrophobic fluorinated peptide dendrons. The spherical morphology, uniform particle size and good storage stability of the prepared FPD-HZN-Dex nanoparticles were characterized by dynamic light scattering and transmission electron microscopy, respectively. In vitro drug release studies showed a controlled and pH dependent hydrophobic drug release profile. The cell viability assays show excellent biocompatibility of the FPD-HZN-Dex nanoparticles for both normal cells and tumor cells. Moreover, the FPD-HZN-Dex self-assembled systems based on pH-sensitive hydrazone linkage also can serve as stimulus bioresponsive carriers for on-demand intracellular drug delivery. These self-assembled nanoparticles exhibit a stimulus-induced response to endo/lysosome pH (pH 5.0) that causes their disassembly over time, enabling controlled release of encapsulated DOX. This work has unveiled a unique non-covalent interaction useful for engineering amphiphilic dendrons or dendrimers self-assembled systems.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, Sichuan, People's Republic of China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Aisha Roshan Mohamed
authors.initials: AR
authors.lastname: Wali
authors.forename: Yiyan
authors.initials: Y
authors.lastname: He
authors.forename: Xianghui
authors.initials: X
authors.lastname: Xu
authors.forename: James Zhenggui
authors.initials: JZ
authors.lastname: Tang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008422:Materials Testing; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D050091:Dendrimers; D003911:Dextrans; D004337:Drug Carriers; D010455:Peptides; D011107:Polylysine; D004317:Doxorubicin