Reactive oxygen species (ROS)-responsive polymersomes with site-specific chemotherapeutic delivery into tumors via spacer design chemistry
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F20%3A00523881" target="_blank" >RIV/61389013:_____/20:00523881 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/20:10411607
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.9b01748" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.9b01748</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.biomac.9b01748" target="_blank" >10.1021/acs.biomac.9b01748</a>
Alternative languages
Result language
angličtina
Original language name
Reactive oxygen species (ROS)-responsive polymersomes with site-specific chemotherapeutic delivery into tumors via spacer design chemistry
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomacromolecules
ISSN
1525-7797
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1437-1449
UT code for WoS article
000526393000009
EID of the result in the Scopus database
2-s2.0-85083621292