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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE · 2015 ·Vol. 26 ·期 8 ·1-13 · IF 2.587

Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery

Ma Shengnan,Zhou Jie,Wali Aisha Roshan Mohamed,He Yiyan,Xu Xianghui,Tang James Zhenggui,Gu Zhongwei

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. Graphical Abstract

研究领域: 生物材料学 · 药剂学 · 纳米医学
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ACS Applied Nano Materials · 2024 · IF 5.3

Fluorinated Peptide Nanoscale Hydrogel Accelerates Wound Healing via pH and Oxygen Microenvironment Regulation

Leixia Mei,Haihong Yang,Weimiao Dong,Min Liu,Jun Han

The abnormal levels of pH and oxygen (O2) in the wound microenvironment impeded wound healing, and their regulation remains a challenge. Thus, a wound dressing with pH and O2-regulating capacity is urgently desired. Here, we designed and prepared a fluorinated peptide hydrogel wound dressing to regulate the pH and O2 microenvironment of the wound site. Fluorinated peptides with the (naphthalene-2-ly)-Gly-5fPhe-5fPhe-Tyr-Arg-Gly-Asp sequence (F5–Pep) could self-assemble to a nanofiber network in a weak acidic buffer (pH = 6.0), which is similar to the pH of human skin. The F5–Pep hydrogel can maintain pH levels at 6.0–7.3 for 24 h and continuously release O2 for 4 h. The blood coagulation and hemostasis assay showed that the F5–Pep hydrogel significantly accelerated blood clotting speed in vitro and rapidly controlled hemorrhage in a mouse liver hemorrhage model. In vitro cell migration assays and in vivo animal experiments confirmed that the F5–Pep hydrogel can promote cell migration and wound healing. In summary, this work might provide an effective treatment strategy for wounds and develop advanced wound-healing materials.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 纳米技术
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ACS Applied Materials & Interfaces · 2017 · IF 7.504

Highly Efficient and Safe Delivery of VEGF siRNA by Bioreducible Fluorinated Peptide Dendrimers for Cancer Therapy

Xiaojun Cai,Haofang Zhu,Yanmei Zhang,Zhongwei Gu

RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.

研究领域: 药剂学 · 分子生物学 · 癌症研究 · 纳米医学
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RSC Advances · 2023 ·Vol. 13 ·期 17 ·11269-11277 · IF 3.9

Improved intracellular delivery of exosomes by surface modification with fluorinated peptide dendrimers for promoting angiogenesis and migration of HUVECs

Shengnan Ma,Lei Song,Yueyue Bai,Shihao Wang,Jiao Wang,Haohao Zhang,Fazhan Wang,Yiyan He,Chuntao Tian,Guijun Qin

Exosomes exhibit great potential as novel therapeutics for tissue regeneration, including cell migration and angiogenesis. However, the limited intracellular delivery efficiency of exosomes might reduce their biological effects. Here, exosomes secreted by adipose-derived mesenchymal stem cells were recombined with fluorinated peptide dendrimers (FPG3) to form the fluorine-engineered exosomes (exo@FPG3), which was intended to promote the cytosolic release and the biological function of exosomes. The mass ratio of FPG3 to exosomes at 5 was used to investigate its cellular uptake efficiency and bioactivity in HUVECs, as the charge of exo@FPG3 tended to be stable even more FPG3 was applied. It was found that exo@FPG3 could enter HUVECs through a variety of pathways, in which the clathrin-mediated endocytosis played an important role. Compared with exosomes modified with peptide dendrimers (exo@PG3) and exosomes alone, the cellular uptake efficiency of exo@FPG3 was significantly increased. Moreover, exo@FPG3 significantly enhanced the angiogenesis and migration of HUVECs in vitro as compared to exo@PG3 and exosomes. It is concluded that surface fluorine modification of exosomes with FPG3 is conducive to the cellular uptake and bioactivity of the exosome, which provides a novel strategy for engineered exosomes to enhance the biological effects of exosome-based drug delivery.

研究领域: 组织工程 · 药物递送 · 细胞生物学 · 干细胞研究
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