Polymer theranostics with multiple stimuli-based activation of photodynamic therapy and tumor imaging

0575824 - ÚMCH 2024 RIV AU eng J - Journal Article
Tavares, Marina Rodrigues - Islam, R. - Šubr, Vladimír - Hackbarth, S. - Gao, S. - Yang, K. - Lobaz, Volodymyr - Fang, J. - Etrych, Tomáš
Polymer theranostics with multiple stimuli-based activation of photodynamic therapy and tumor imaging.
Theranostics. Roč. 13, č. 14 (2023), s. 4952-4973. ISSN 1838-7640. E-ISSN 1838-7640
R&D Projects: GA MZd(CZ) NU21-08-00280; GA MŠMT LX22NPO5102
Grant - others:AV ČR(CZ) JSPS-22-01
Program: Bilaterální spolupráce
Institutional support: RVO:61389013
Keywords : fluorescence imaging * photodynamic therapy * pH-responsive theranostics
OECD category: Polymer science
Impact factor: 12.4, year: 2022
Method of publishing: Open access
https://www.thno.org/v13p4952

Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers. Here, we develop stimuli-sensitive theranostics consisting of tailored copolymers forming micellar conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds, thus enabling the tumor microenvironment-sensitive activation of the photodynamic therapy (PDT) effect, fluorescence or phosphorescence. The nanomedicines show superior anti-tumor PDT efficacy and huge tumor-imaging potential, while reducing their accumulation, and potentially side effects, in the liver and spleen. The developed theranostics exhibit clear selective tumor accumulation at high levels in the mouse sarcoma S180 tumor model with almost no PyF found in the healthy tissues after 48 h. Once in the tumor, illumination at λexc = 420 nm reaches the therapeutic effect due to the 1O2 generation. Indeed, an almost complete inhibition of tumor growth is observed up to 18 days after the treatment. The clear benefit of the specific PyF release and activation in the acidic tumor environment for the targeted delivery and tissue distribution dynamics was proved. Conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds showed their excellent antitumor PDT effect and its applicability as advanced theranostics at very low dose of PyF.
Permanent Link: https://hdl.handle.net/11104/0346030