Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

Bоrodinа, Tatyana N.; Kostyushev, Dmitry; Zamyatnin, Andrey A.; Parodi, Alessandro

doi:10.3390/ijtm1030018

Cited by 9 publications

(5 citation statements)

References 130 publications

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“…[38][39][40]. EVs are under clinical investigation for therapy of autoimmune diseases, in regenerative medicine etc [3,41,42]. However, EVs are hard to manufacture, their production is fraught with low yields of NPs, high heterogeneity, complex isolation, purification and characterization making medical-grade EVs production process to hardly meet the GMP standards, while skyrocketing the costs [12].…”

Section: Discussionmentioning

confidence: 99%

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles per se and Those Fused with Liposomes in Acidic Environment

Ponomareva,

Brezgin,

Karandashov

et al. 2024

Preprint

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Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to acidic environment observed in endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline of their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid endolysosomal compartment whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge associated with scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs, and indicate that EMNVs are more efficient in escaping or avoiding endolysosomal compartment.

show abstract

Section: Discussionmentioning

confidence: 99%

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles per se and Those Fused with Liposomes in Acidic Environment

Ponomareva,

Brezgin,

Karandashov

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…EVs are under clinical investigation for therapy of autoimmune diseases, in regenerative medicine, etc. [3,42,43]. However, EVs are hard to manufacture, and their production is fraught with low yields of NPs, high heterogeneity, complex isolation, purification and characterization, making the medical-grade EV production process hard to meet the GMP's standards while skyrocketing the costs [12].…”

Section: Discussionmentioning

confidence: 99%

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles Per Se and Those Fused with Liposomes in Acidic Environment

Ponomareva,

Brezgin,

Karandashov

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to the acidic environment observed in the endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline in their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid the endolysosomal compartment, whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge-associated scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding the endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs and indicate that EMNVs are more efficient in escaping or avoiding the endolysosomal compartment.

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“…Unfortunately, while in preclinical settings these technologies provided promising results, their clinical translation was hampered by their high costs of production and sometimes by issues of generating nanoformulations in large scale [ 15 , 16 ]. However, the research in the field is still very active and supported by the exploration of alternative administration routes other than intravenous [ 17 , 18 ] and by the development of other applications, including diagnosis. The goal of this review is to summarize the nanocarriers that reached clinical trial experimentation and some examples to the readers about the characteristics that nanoformulations should have to treat the patients, including their size and targeting mechanism.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Nanotherapeutics in Clinical Trials: The Work behind Clinical Translation of Nanomedicine

Parodi

Kolesova

Voronina

et al. 2022

IJMS

Self Cite

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The ultimate goal of nanomedicine has always been the generation of translational technologies that can ameliorate current therapies. Cancer disease represented the primary target of nanotechnology applied to medicine, since its clinical management is characterized by very toxic therapeutics. In this effort, nanomedicine showed the potential to improve the targeting of different drugs by improving their pharmacokinetics properties and to provide the means to generate new concept of treatments based on physical treatments and biologics. In this review, we considered different platforms that reached the clinical trial investigation, providing an objective analysis about their physical and chemical properties and the working mechanism at the basis of their tumoritr opic properties. With this review, we aim to help other scientists in the field in conceiving their delivering platforms for clinical translation by providing solid examples of technologies that eventually were tested and sometimes approved for human therapy.

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Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

Cited by 9 publications

References 130 publications

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles per se and Those Fused with Liposomes in Acidic Environment

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles per se and Those Fused with Liposomes in Acidic Environment

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles Per Se and Those Fused with Liposomes in Acidic Environment

Anticancer Nanotherapeutics in Clinical Trials: The Work behind Clinical Translation of Nanomedicine

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