HPMA-based copolymers carrying STAT3 inhibitor cucurbitacin-D as stimulus-sensitive nanomedicines for oncotherapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F21%3A00539979" target="_blank" >RIV/61388971:_____/21:00539979 - isvavai.cz</a>
Alternative codes found
RIV/61389013:_____/21:00539979
Result on the web
<a href="https://www.mdpi.com/1999-4923/13/2/179" target="_blank" >https://www.mdpi.com/1999-4923/13/2/179</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/pharmaceutics13020179" target="_blank" >10.3390/pharmaceutics13020179</a>
Alternative languages
Result language
angličtina
Original language name
HPMA-based copolymers carrying STAT3 inhibitor cucurbitacin-D as stimulus-sensitive nanomedicines for oncotherapy
Original language description
The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition–fragmentation chain transfer polymerization to reach molecular weight Mn about 2 × 104 g·mol−1 and low dispersity. These linear or self-assembled micellar conjugates, containing immunomodulatory agent cucurbitacin-D (CuD) or the anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond, showed a hydrodynamic size of 10–30 nm in aqueous solutions. The CuD-containing conjugates were stable in conditions mimicking blood. Importantly, a massive release of active CuD in buffer mimicking the acidic tumor environment was observed. In vitro, both the linear (LP-CuD) and the micellar (MP-CuD) conjugates carrying CuD showed cytostatic/cytotoxic activity against several cancer cell lines. In a murine metastatic and difficult-to-treat 4T1 mammary carcinoma, only LP-CuD showed an anticancer effect. Indeed, the co-treatment with Dox-containing micellar polymer conjugate and LP-CuD showed potentiation of the anticancer effect. The results indicate that the binding of CuD, characterized by prominent hydrophobic nature and low bioavailability, to the polymer carrier allows a safe and effective delivery. Therefore, the conjugate could serve as a potential component of immuno-oncotherapy schemes within the next preclinical evaluation.
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
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmaceutics
ISSN
1999-4923
e-ISSN
1999-4923
Volume of the periodical
13
Issue of the periodical within the volume
2
Country of publishing house
CH - SWITZERLAND
Number of pages
17
Pages from-to
179
UT code for WoS article
000623000700001
EID of the result in the Scopus database
2-s2.0-85100458304