Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release

M V Novoselova; E I Shramova; O V Sergeeva; E Y Shcherbinina; S V Perevoschikov; P Melnikov; O Yu Griaznova; I S Sergeev; E V Konovalova; A A Schulga; G M Proshkina; T S Zatsepin; S M Deyev; D A Gorin

doi:10.1016/j.nano.2022.102612

Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release

Nanomedicine. 2023 Jan:47:102612. doi: 10.1016/j.nano.2022.102612. Epub 2022 Oct 13.

Authors

M V Novoselova¹, E I Shramova², O V Sergeeva³, E Y Shcherbinina⁴, S V Perevoschikov⁵, P Melnikov⁶, O Yu Griaznova⁷, I S Sergeev⁵, E V Konovalova², A A Schulga², G M Proshkina⁸, T S Zatsepin⁹, S M Deyev², D A Gorin¹⁰

Affiliations

¹ Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: [email protected].
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.
³ Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: [email protected].
⁴ Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: [email protected].
⁵ Skolkovo Institute of Science and Technology, Moscow 121205, Russia.
⁶ V. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia.
⁷ Skolkovo Institute of Science and Technology, Moscow 121205, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia. Electronic address: [email protected].
⁸ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia. Electronic address: [email protected].
⁹ Lomonosov Moscow State University, Moscow 119991, Russia. Electronic address: [email protected].
¹⁰ Skolkovo Institute of Science and Technology, Moscow 121205, Russia. Electronic address: [email protected].

PMID: 36243307
DOI: 10.1016/j.nano.2022.102612

Abstract

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2-) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.

Keywords: DARPin; Doxorubicin; Drug delivery carriers; Focused ultrasound induced release; Freezing induced loading; Layer-by-layer assembly; Low intensity focused ultrasound; Lysosomes uptake avoid; Mitochondria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Doxorubicin / pharmacology
Ferrosoferric Oxide*
Nanomedicine
Polymers*

Substances

Ferrosoferric Oxide
Polymers
Doxorubicin