Reactive oxygen species (ROS)-responsive polymersomes with site-specific chemotherapeutic delivery into tumors via spacer design chemistry

Jäger, Eliezer; Sincari, Vladimir; Albuquerque, L. J. C.; Jäger, Alessandro; Humajová, J.; Kučka, Jan; Pankrác, J.; Páral, P.; Heizer, T.; Janoušková, Olga; Konefal, Rafal; Pavlova, Ewa; Sedláček, Ondřej; Giacomelli, F. C.; Poučková, P.; Šefc, L.; Štěpánek, Petr; Hrubý, Martin

doi:https://dx.doi.org/10.1021/acs.biomac.9b01748

Number of the records: 1

Reactive oxygen species (ROS)-responsive polymersomes with site-specific chemotherapeutic delivery into tumors via spacer design chemistry

1.

SYSNO ASEP	0523881
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Reactive oxygen species (ROS)-responsive polymersomes with site-specific chemotherapeutic delivery into tumors via spacer design chemistry
Author(s)	Jäger, Eliezer (UMCH-V)_{ORCID, RID} Sincari, Vladimir (UMCH-V)_{ORCID, RID} Albuquerque, L. J. C. (BR) Jäger, Alessandro (UMCH-V)_{RID, ORCID} Humajová, J. (CZ) Kučka, Jan (UMCH-V)_{RID, ORCID} Pankrác, J. (CZ) Páral, P. (CZ) Heizer, T. (CZ) Janoušková, Olga (UMCH-V)_{RID, SAI, ORCID} Konefal, Rafal (UMCH-V)_{RID, ORCID} Pavlova, Ewa (UMCH-V)_RID Sedláček, Ondřej (UMCH-V)_{RID, ORCID} Giacomelli, F. C. (BR) Poučková, P. (CZ) Šefc, L. (CZ) Štěpánek, Petr (UMCH-V)_{RID, ORCID} Hrubý, Martin (UMCH-V)_{RID, ORCID}
Source Title	Biomacromolecules. - : American Chemical Society - ISSN 1525-7797 Roč. 21, č. 4 (2020), s. 1437-1449
Number of pages	13 s.
Language	eng - English
Country	US - United States
Keywords	polyredoxomes ; block copolymer ; reactive oxygen species
Subject RIV	CD - Macromolecular Chemistry
OECD category	Polymer science
R&D Projects	GA17-09998S GA ČR - Czech Science Foundation (CSF)
	8J18FR038 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	NV16-30544A GA MZd - Ministry of Health (MZ)
	TN01000008 GA TA ČR - Technology Agency of the Czech Republic (TA ČR)
Research Infrastructure	Czech-BioImaging - 90062 - Ústav molekulární genetiky AV ČR, v. v. i.
Method of publishing	Limited access
Institutional support	UMCH-V - RVO:61389013
UT WOS	000526393000009
EID SCOPUS	85083621292
DOI	10.1021/acs.biomac.9b01748
Annotation	The lack of cellular and tissue specificities in conventional chemotherapies along with the generation of a complex tumor microenvironment (TME) limits the dosage of active agents that reaches tumor sites, thereby resulting in ineffective responses and side effects. Therefore, the development of selective TME-responsive nanomedicines is of due relevance toward successful chemotherapies, albeit challenging. In this framework, we have synthesized novel, ready-to-use ROS-responsive amphiphilic block copolymers (BCs) with two different spacer chemistry designs to connect a hydrophobic boronic ester-based ROS sensor to the polymer backbone. Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was used in the preparation of well-defined ROS-responsive PSs. These were further characterized by a combination of techniques [1H NMR, dynamic light scattering (DLS), static light scattering (SLS), transmission electron microscopy (TEM), and cryogenic TEM (cryo-TEM)]. The reaction with hydrogen peroxide releases an amphiphilic phenol or a hydrophilic carboxylic acid, which affects polymersome (PS) stability and cargo release. Therefore, the importance of the spacer chemistry in BC deprotection and PS stability and cargo release is herein highlighted. We have also evaluated the impact of spacer chemistry on the PS-specific release of the chemotherapeutic drug doxorubicin (DOX) into tumors in vitro and in vivo. We demonstrate that by spacer chemistry design one can enhance the efficacy of DOX treatments (decrease in tumor growth and prolonged animal survival) in mice bearing EL4 T cell lymphoma. Side effects (weight loss and cardiotoxicity) were also reduced compared to free DOX administration, highlighting the potential of the well-defined ROS-responsive PSs as TME-selective nanomedicines. The PSs could also find applications in other environments with high ROS levels, such as chronic inflammations, aging, diabetes, cardiovascular diseases, and obesity.
Workplace	Institute of Macromolecular Chemistry
Contact	Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
Year of Publishing	2021
Electronic address	https://pubs.acs.org/doi/10.1021/acs.biomac.9b01748

Number of the records: 1