Chemical modification of bradykinin-polymer conjugates for optimum delivery of nanomedicines to tumors

0584601 - ÚMCH 2025 RIV NL eng J - Článek v odborném periodiku
Appiah, E. - Nakamura, H. - Assumang, A. - Etrych, Tomáš - Haratake, M.
Chemical modification of bradykinin-polymer conjugates for optimum delivery of nanomedicines to tumors.
Nanomedicine: Nanotechnology, Biology and Medicine. Roč. 57, April (2024), č. článku 102744. ISSN 1549-9634. E-ISSN 1549-9642
Grant CEP: GA MŠMT LX22NPO5102
Institucionální podpora: RVO:61389013
Klíčová slova: bradykinin * HPMA polymer * controlled release
Obor OECD: Polymer science
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S1549963424000133?via%3Dihub

We recently prepared pH-responsive HPMA copolymer conjugates of bradykinin (P-BK), which release BK in response to the acidic tumor microenvironment, and found that administration of P-BK increased the tumor accumulation and therapeutic efficacy of nanomedicine. Because the release of BK from P-BK determines its onset of action, P-BKs with different release rates were prepared, and their properties were evaluated. The release kinetics were significantly altered by substitution proximal to hydrazone bond, release constant of methyl-substituted P-BK (P-MeBK) was approximately 4- and 80-fold higher than that of cyclopropyl-substituted P-BK (P-CPBK) and phenyl-substituted P-BK (P-PhBK). None of the P-BKs were active, but the release of BK restored their BK-like activity. Pre-administration of the P-BKs increased the tumor accumulation of nanomedicine in C26 tumor-bearing mice by 2- and 1.4-fold for P-MeBK and P-PhBK at 3 and 6 h. Altogether, this study provides insights into the design of pH-responsive nanodrugs with the desired release properties to target acidic lesions such as cancer and inflammation.
Trvalý link: https://hdl.handle.net/11104/0352525