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Subbotin, V.

Publications and source records attributed to Subbotin, V..

2 recordsLinked to original sources

Nighttime and daytime scenarios in Darwinian liposome evolution under UV-driven natural selection

Previously, we presented a hypothesis on Darwinian evolution of liposomes that relies solely on natural and ever-present phenomena: the day-night cycle of solar UV radiation, gravity, and the release of amphiphiles in aqueous media. We demonstrated the protective ability of certain ferric salts typical for Archean waters, notably iron trichloride and ferric ammonium citrate, against liposome destruction by short-wavelength UV by shielding the liposomes with cuvettes filled with ferric salts. In the present study, we investigate the interaction with UV for the liposomes with negative buoyancy that sink naturally in ferric salt solutions. We examined two scenarios: 1) liposomes submerged in the FeCl3 solution prior to the UV exposure, a scenario mimicking the nighttime submergence; and 2) submergence under UV exposure, a relevant daytime scenario. We use custom-designed micron-sized, negative-buoyant (heavy), UV-sensitive liposomes. The results showed that for the nighttime scenario, all liposomes were free from UV damage when given sufficient time to submerge in a protective ferric salt solution. Given that larger and heavier liposomes submerge faster, we hypothesize that simple sugar molecules, such as ribose, which is a vital component of RNA, can serve as the proposed heavy molecules in Origin of Life scenarios. Conversely, the daytime scenario results indicate that liposomes slowly submerging under UV exposure sustain some damage. The results of these experiments, which aim to simulate natural events, showed that negative buoyancy and short-wavelength UV radiation could serve as natural drivers in the novel scenario of Darwinian liposome evolution.

evolutionary biology↗

Bispecific GD2 x B7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma

The current treatment for neuroblastoma involves an immunotherapy regimen that includes a monoclonal antibody that recognizes disialoganglioside (GD2), expressed at high levels on neuroblastoma. GD2 is not present on most normal tissues but is expressed on nerves. Thus, anti-GD2 treatment causes substantial, dose-limiting, neuropathic pain. B7-H3 is overexpressed on multiple tumor types, including neuroblastoma, with minimal normal cell expression and is absent on nerves. We designed a bispecific antibody (bsAb) that requires simultaneous binding of these two tumor antigens to achieve tight-binding of tumor cells. Our preclinical research shows that when compared to an anti-GD2 monospecific antibody, the GD2xB7-H3 bsAb has improved tumor specificity with similar efficacy and reduced toxicity. Since this bsAb does not bind to nerves, it may be possible to administer increased or additional doses beyond the tolerable dose of monospecific anti-GD2 antibodies, which could improve therapeutic efficacy and quality of life for patients with neuroblastoma.

cancer biology↗