Internalized FGF-2-Loaded Nanoparticles Increase Nuclear ERK1/2 Content and Result in Lung Cancer Cell Death

Miao, Tianxin; Little, Andrew C.; Aronshtam, Alexander; Marquis, Taylor; Fenn, S.; Hristova, Milena; Krementsov, Dimitry N.; Vliet, Albert van der; Spees, Jeffrey L.; Oldinski, Rachael A.

doi:10.3390/nano10040612

Cited by 11 publications

(8 citation statements)

References 63 publications

(83 reference statements)

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“…FGF-2 or FGF-1 were also usually released for no longer than 12 days from different types of Alg hydrogels, i.e., microbeads prepared by needle extrusion or air stripping [ 47 , 52 ], bulk scaffolds [ 53 , 54 ], nanoparticles prepared from pegylated Alg using the emulsion technique [ 55 ], and microgels prepared by the microfluidic approach [ 56 ]. High-M Alg delivery systems delivered FGF-2 mostly within a few hours, then a minimal release of 1 to 5% was detected [ 52 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

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Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

Adrian

Treľová

Filová

et al. 2021

IJMS

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Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.

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Section: Resultsmentioning

confidence: 99%

“…In our study, only 50% of the total FGF-2 amount was released within 48 h, and then the release gradually continued for one month ( Figure 5 A). The short-term release for several days approaching sustained release profiles has been reported only for highly crosslinked high-G Alg particles [ 47 , 55 , 56 ].…”

Section: Resultsmentioning

confidence: 99%

Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

Adrian

Treľová

Filová

et al. 2021

IJMS

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“…Recombinant human FGF2 (18 kDa) was purified from a bacterial expression system ( Escherichia coli strain BL21), as reported previously ( Miao et al, 2020 ). Briefly, bacteria were grown in Luria-Bertani (LB) broth with ampicillin.…”

Section: Methodsmentioning

confidence: 99%

“…Purified FGF2, Jagged1-Fc, or IgG were run individually (i.e., free) or as FGF2/IgG or FGF2/Jagged1- Fc complexes to assess their respective mobilities. Human FGF2 was cloned, expressed, and purified in our laboratory ( Rao et al, 2015 ; Miao et al, 2020 ). Jagged1- Fc was commercial (R&D Systems).…”

Section: Methodsmentioning

confidence: 99%

Human Growth Factor/Immunoglobulin Complexes for Treatment of Myocardial Ischemia-Reperfusion Injury

Liebman

Schwaegler

Foote

et al. 2022

Front. Bioeng. Biotechnol.

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Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor 2 (FGF2) are receptor tyrosine kinase agonists that promote cell survival after tissue injury and angiogenesis, cell proliferation and migration during tissue repair and regeneration. Both ligands have potential as systemic treatments for ischemia-reperfusion injury, however clinical use of HGF and FGF2 has been limited by poor pharmacokinetic profiles, i.e., their susceptibility to serum proteases, rapid clearance and short half-lives. Previously, we reported vaso- and cardioprotective protein complexes formed between HGF and polyclonal, non-specific immunoglobulin (IgG) with therapeutic efficacy in a rat model of myocardial ischemia with reperfusion (MI/R). Here, using a pre-clinical porcine MI/R model, we demonstrate human HGF/IgG complexes provide significant myocardial salvage, reduce infarct size, and are detectable in myocardial tissue 24 h after intracoronary injection. Furthermore, we show that multiple daily infusions of HGF/IgG complexes after MI do not lead to production of HGF-specific auto-antibodies, an important concern for administered biologic drugs. In experiments to identify other growth factors that non-covalently interact with IgG, we found that human FGF2 associates with IgG. Similar to human HGF/IgG complexes, FGF2/IgG complexes protected primary human cardiac endothelial cells under simulated ischemia (1% oxygen and nutrient deprivation) for 48–72 h. Molecular modeling studies suggested that FGF2 and HGF both interact with the Fc domain of IgG. Also, we tested whether an Fc-fusion protein would bind FGF2 to form complexes. By native gel electrophoretic assays and biochemical pulldowns, we found that Jagged1, a Notch1 ligand that controls stem cell self-renewal and tissue regeneration, bound FGF2 when presented as a Jagged1- Fc fusion protein. Our results suggest that human growth factor/IgG and FGF2/Fc- fusion complexes have potential to provide a biologics platform to treat myocardial ischemia-reperfusion and other forms of tissue injury.

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“…In contrast, the most pressing challenge is application of nanotechnology to design of multifunctional, structured materials able to target specific diseases and protection of therapeutic moieties [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Functionalities to allow transport across biological barriers and to realize the desired clinical benefits rapidly via understanding of toxicological implications of nanomedicines relate to the specific nanoscale properties [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. The potential environmental impact and a safety assessment of all manufacturing processes require a case-by-case approach to clinical and regulatory evaluation of each nanopharmaceutical.…”

Section: Introductionmentioning

confidence: 99%

Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates

et al. 2020

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The fabrication and development of nanomaterials for the treatment of prostate cancer have gained significant appraisal in recent years. Advancements in synthesis of organic and inorganic nanomaterials with charge, particle size, specified geometry, ligand attachment etc have resulted in greater biocompatibility and active targeting at cancer site. Despite all of the advances made over the years in discovering drugs, methods, and new biomarkers for cancer of the prostate (PCa), PCa remains one of the most troubling cancers among people. Early on, effective diagnosis is an essential part of treating prostate cancer. Prostate-specific antigen (PSA) or serum prostate-specific antigen is the best serum marker widely accessible for diagnosis of PCa. Numerous efforts have been made over the past decade to design new biosensor-based strategies for biomolecules detection and PSA miniaturization biomarkers. The growing nanotechnology is expected to have a significant effect in the immediate future on scientific research and healthcare. Nanotechnology is thus predicted to find a way to solve one of the most and long-standing problem, “early cancer detection”. For early diagnosis of PCa biomarkers, different nanoparticles with different approaches have been used. In this review, we provide a brief description of the latest achievements and advances in the use of nanoparticles for PCa biomarker diagnosis.

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Internalized FGF-2-Loaded Nanoparticles Increase Nuclear ERK1/2 Content and Result in Lung Cancer Cell Death

Cited by 11 publications

References 63 publications

Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads

Human Growth Factor/Immunoglobulin Complexes for Treatment of Myocardial Ischemia-Reperfusion Injury

Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates

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