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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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

  • 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