Nanodelivery of doxorubicin for age-related macular degeneration

Kelly, Shannon; Halasz, Kathleen; Smalling, Rudy; Sutariya, Vijaykumar

doi:10.1080/03639045.2019.1569024

Cited by 15 publications

(6 citation statements)

References 26 publications

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“…After loading the drug with different methods, unencapsulated Dox was removed by ultrafiltration using Amicon ultra centrifugal filters (10 kDa, Millipore, Billerica, MA, USA) at 14,000× g for 15 min. The concentration of Dox in PBS was quantified by measuring the optical density at 480 nm on a microplate reader (Synergy 2, BioTek, Winooski, VT, USA) [ 16 ]. The drug encapsulation efficiency (EE%) was calculated by dividing the amount of loaded drug by that of the total drug.…”

Section: Methodsmentioning

confidence: 99%

Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

Yang

Guan

Pang

et al. 2022

Cells

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Hepatocellular carcinoma (HCC) is one of the dominating causes of cancer-related death throughout the world. Treatment options for patients with HCC vary, however, the lack of effective targeted drugs is the major reason for death in advanced HCC patients. In this study, a delivery system based on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) loaded with doxorubicin (Dox) was developed. In this system, we initially erased terminal linked α2–3 and α2–6 sialic acids on the surface of EVs by neuraminidase. The exhibition of galactose (Gal) and N-acetylgalactosamine (GalNAc) residues in treated MSC-EVs can specifically be recognized by asialoglycoprotein receptor (ASGPR) of hepatoma cells. Compared to free Dox and Dox-loaded EVs, desialylated EVs loaded with Dox significantly presented the improved cellular uptake, prioritized targeting efficacy, and had a better inhibiting effect in vitro and in vivo. Overall, the results of the present study of the demonstrated delivery system using desialylated MSC-EVs suggest its therapeutic potential for HCC.

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Section: Methodsmentioning

confidence: 99%

Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

Yang

Guan

Pang

et al. 2022

Cells

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“…SEM imaging revealed that spherical NPs possess a high surface area to volume ratio compared to other shapes (rod, cubic, etc.) which produce a more reactive surface and opportunities to therapeutic effects [17] . In the study of transfection of MSCs with PLGA NPs, MSCs demonstrated both concentration and time dependent uptake of NPs, with very little effect on cell viability [20] .…”

Section: Discussionmentioning

confidence: 99%

A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA -loaded nanoparticles on RPE cells under hypoxia environment

Zhang

Yan

Li³

et al. 2022

Preprint

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AIM: To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of HIF-1α siRNA between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed by Genechem company. HIF-1α siRNA was encapsulated into Poly (lactic-co-glycolic acid)(PLGA) nanoparticles(NPs) through the water-in-oil-in-water (W/O/W) multiple emulsion technique. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Then a transwell co-culture system of MSCs and RPE was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect on HIF-1α expression of RPE cells was analyzed by using quantitative polymerase chain reaction at the time point 24 h, 3 d and 7 d.RESULTS: The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1nm and the zeta potential was﹣0.36 mV. The transfection efficiency of PLGA NPs was (67.3%±5.2%) into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7 days in RPE (0.63±0.05 at 7d, P < 0.001). In the transwell co-culture system of MSCs and RPE, the abilities of proliferation(2.34±0.17 vs 2.40 ± 0.28 vs2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83 ± 2.43% vs 12.94 ± 2.19% vs 12.39 ± 3.21%; F= 0.70, P=0.53) and migration(124.5± 7.78 vs 119.5± 5.32 vs 130±9.89, F =1.33, P=0.33) of the RPE cells had no differences between MSC-loaded HIF-1α siRNA PLGA-NPs group and other groups. The inhibition of PLGA on the HIF-1α mRNA expression in RPE cells could continue until the 7th day, the level of HIF-1α mRNA was lower than that of other groups (F=171.98, P <0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α siRNA carried by MSCs is found to be beneficial temporally for HIF-1α mRNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α siRNA nanoparticles is a potential method for therapy against choroidal neovascularization (CNV).

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“…Cun et al [17] incorporated the siRNA in PLGA NPs by using a double emulsion solvent evaporation method, and optimized the formulations of PLGA by varying the siRNA and PLGA ratio which achieved the encapsulation efficiency of more than 70%. In many studies, the size of PLGA NPs prepared by the same method was about 200 nm, and the surface charge was negative [18][19] . In this study, the average diameter of PLGA NPs loaded-HIF siRNA was 314.1 nm but with a rather narrow size distribution, and zeta potential was similar to other studies, showing -0.36 mV.…”

Section: Effect Of Mesenchymal Stem Cells Loaded With Hif-1α Sirna Na...mentioning

confidence: 99%

“…SEM imaging revealed that spherical NPs possess a high surface area to volume ratio compared to other shapes (rod, cubic, etc.) which produce a more reactive surface and opportunities to therapeutic effects [18] . In the study of transfection of MSCs with PLGA NPs, MSCs demonstrated both concentration and time dependent uptake of NPs, with very little effect on cell viability [21] .…”

Section: Effect Of Mesenchymal Stem Cells Loaded With Hif-1α Sirna Na...mentioning

confidence: 99%

A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA-loaded nanoparticles on retinal pigment epithelial cells under hypoxia environment

Zhang¹,

Wang²,

Li³

et al. 2022

Int J Ophthalmol

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AIM: To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxia-inducible factor-1α small interfering RNA (HIF-1α siRNA) between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment. METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α siRNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) through the water-in-oil-in-water (w/o/w) multiple emulsion technique. The effect of PLGA-NPs uptake on the expression of HIF-1α mRNA was tested in RPE cells by real-time quantitative polymerase chain reaction (qPCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using qPCR at the time points 24h, 3d, and 7d. RESULTS: The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1 nm and the zeta potential was -0.36 mV. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7d in RPE (0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation (2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis (14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%; F=0.70, P=0.53) and migration (124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSC-loaded HIF-1α siRNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α mRNA expression in RPE cells could continue until the 7th day, the level of HIF-1α mRNA was lower than that of other groups (F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α siRNA carried by MSCs is found to be beneficial temporally for HIF-1α mRNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α siRNA nanoparticles is a potential method for therapy against choroidal neovascularization.

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Nanodelivery of doxorubicin for age-related macular degeneration

Cited by 15 publications

References 26 publications

Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA -loaded nanoparticles on RPE cells under hypoxia environment

A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA-loaded nanoparticles on retinal pigment epithelial cells under hypoxia environment

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