All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

Improved tumor-specific drug accumulation by polymer therapeutics with pH-sensitive drug release overcomes chemotherapy resistance

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00460441" target="_blank" >RIV/61389013:_____/16:00460441 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1158/1535-7163.MCT-15-0824" target="_blank" >http://dx.doi.org/10.1158/1535-7163.MCT-15-0824</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1158/1535-7163.MCT-15-0824" target="_blank" >10.1158/1535-7163.MCT-15-0824</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Improved tumor-specific drug accumulation by polymer therapeutics with pH-sensitive drug release overcomes chemotherapy resistance

  • Original language description

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA–doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA–doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging–based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CD - Macromolecular chemistry

  • OECD FORD branch

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

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Molecular Cancer Therapeutics

  • ISSN

    1535-7163

  • e-ISSN

  • Volume of the periodical

    15

  • Issue of the periodical within the volume

    5

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    10

  • Pages from-to

    998-1007

  • UT code for WoS article

    000375857400021

  • EID of the result in the Scopus database

    2-s2.0-84969579569