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Theranostics 2023; 13(14):4952-4973. doi:10.7150/thno.86211 This issue Cite

Research Paper

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

Marina Rodrigues Tavares^1#, Rayhanul Islam^2#, Vladimír Šubr¹, Steffen Hackbarth³, Shanghui Gao², Kai Yang², Volodymyr Lobaz¹, Jun Fang^2✉, Tomáš Etrych^1✉

1. Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 16200 Prague, Czech Republic.
2. Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
3. Institute of Physics, Photobiophysics, Humboldt University of Berlin, Newtonstr. 15, 12489 Berlin, Germany.
# These authors contributed equally to this paper.

✉ Corresponding authors: E-mail address: etrychcas.cz, fangjunsojo-u.ac.jp.

Abstract

Background: Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers.

Goals of the Investigation: 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.

Results: 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 λ_exc = 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.

Conclusion: 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.

Keywords: fluorescence imaging, photodynamic therapy, pH-responsive theranostics, HPMA polymers, tumor-targeted nanomedicines

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