Clodronate-loaded liposomal and fibroblast-derived exosomal hybrid system for enhanced drug delivery to pulmonary fibrosis

Sun, Lingna; Fan, Mingrui; Dong, Hongjuan; Li, Bingqin; Xu, Ruoting; Gao, Feng; Chen, Yanzuo

doi:10.1016/j.biomaterials.2021.120761

Cited by 106 publications

(92 citation statements)

References 45 publications

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“…More recently, the delivery potentials of hybrid of exosomes and liposomes were assessed in vivo for targeted pulmonary fibrosis therapy, which has been challenging in the clinic for insufficient drug concentration and poor targeting. Sun et al developed a clodronate (CLD)-loaded hybrid drug delivery system, consisted of liposome and fibroblast-derived exosomes with properties preventing phagocytosis and targeting fibroblast, for the treatment of pulmonary fibrosis [ 101 ]. The HEs efficiently accumulated in the fibrotic lesion and exhibited significant penetration of pulmonary fibrotic tissue for the improved affinity for fibroblasts by homologous exosome.…”

Section: Artificial Exosomes By Nanobiotechnologymentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

et al. 2021

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Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

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Section: Artificial Exosomes By Nanobiotechnologymentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

et al. 2021

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“…In our previous studies, we demonstrated good biocompatibility of LIEV with no effects on L-929 cell growth and weak cytotoxic effects on fibroblasts by CLD liposomes. 27 Thus, the therapeutic effects on fibrosis in vitro were mainly attributable to the anti-fibrosis agent, NIN, in the liposomes (Fig. 1F).…”

Section: Papermentioning

confidence: 93%

“…Biomaterials Science in the literature. 27 Briefly, DOPC, cholesterol and DSPE-PEG 2000 in the lipid formula were at a molar ratio of 2 : 10 : 1 and were dissolved with 8 mg of NIN in 5 mL of chloroform, dried into a thin film on a rotary evaporator, and then suspended in chloroform as an oil phase. 2 mL of CLD solution (20 mg mL −1 ) was gradually added to the oil phase and further emulsified by stirring.…”

Section: Papermentioning

confidence: 99%

“…To screen for the appropriate ratio of liposomes and EVs, a fluorescence resonance energy transfer (FRET) study was conducted as previously reported by our group. 27 Briefly, 2% (w/w) DOPC of the liposomal formulation was replaced by PE-NBD and PE-RhB in equal amounts. The liposome extrusion with EVs was then analyzed by fluorescence spectroscopy (F-4600, Hitachi, Japan) at an excitation wavelength of 470 nm and the emission spectra between 500 and 650 nm were measured.…”

Section: Papermentioning

confidence: 99%

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Clodronate-nintedanib-loaded exosome–liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity

Fan

Dong

et al. 2022

Biomater. Sci.

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“…Exosomes are small (diameter of ∼ 30–200 nm) single-membrane vesicles derived from intracellular bodies. A number of evidences show that exosomes exist in almost all mammalian cells [ 5 – 7 ]. In cellular communication, exosomes deliver effectors such as proteins, mRNAs, or microRNAs (miRNAs/miRs) to regulate the functions of recipient cells or tissues [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling

Yao

Xiong

et al. 2021

J Nanobiotechnol

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Background Exosomes are extracellular vesicles of nano-structures and represent an emerging nano-scale acellular therapy in recent years. Tendon regeneration is a sophisticated process in the field of microsurgery due to its poor natural healing ability. To date, no successful long-term solution has been provided for the healing of tendon injuries. Functional recovery requires advanced treatment strategies. Human umbilical cord mesenchymal stem cell-derived exosomes (HUMSC-Exos) are considered as promising cell-free therapeutic agents. However, few studies reported their potential in the tendon repair previously. In this study, we explored the roles and underlying mechanisms of HUMSC-Exos in the tendon regeneration. Results Expression of tendon‐specific markers in, and collagen deposition by, tendon-derived stem cells (TDSCs) treated with HUMSC-Exos increased in vitro. In a rat Achilles tendon injury model, treatment with HUMSC-Exos improved the histological structure, enhanced tendon-specific matrix components, and optimized biomechanical properties of the Achilles tendon. Findings in miRNA sequencing indicated a significant increase in miR-29a-3p in HUMSC-Exo-treated Achilles tendons. Next, luciferase assay in combination with western blot identified phosphatase and tensin homolog (PTEN) as the specific target of miR-29a-3p. Furthermore, we applied a miR-29a-3p-specific agonist to engineer HUMSC-Exos. These HUMSC-Exos overexpressing miR-29a-3p amplified the gain effects of HUMSC-Exos on tendon healing in vivo. To explore the underlying mechanisms, a transforming growth factor-β1 (TGF-β1) inhibitor (SB-431542), mTOR inhibitor (rapamycin), and engineered HUMSC-Exos were employed. The results showed that TGF-β1 and mTOR signaling were involved in the beneficial effects of HUMSC-Exos on tendon regeneration. Conclusion The findings in our study suggest that PTEN/mTOR/TGF-β1 signaling cascades may be a potential pathway for HUMSC-Exos to deliver miR-29a-3p for tendon healing and implicate a novel therapeutic strategy for tendon regeneration via engineered stem cell-derived exosomes. Graphic abstract

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Clodronate-loaded liposomal and fibroblast-derived exosomal hybrid system for enhanced drug delivery to pulmonary fibrosis

Cited by 106 publications

References 45 publications

Artificial exosomes for translational nanomedicine

Artificial exosomes for translational nanomedicine

Clodronate-nintedanib-loaded exosome–liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity

MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling

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