Cascade In Situ Self‐Assembly and Bioorthogonal Reaction Enable the Enrichment of Photosensitizers and Carbonic Anhydrase Inhibitors for Pretargeted Cancer Theranostics

Author:

Wen Xidan1,Zeng Wenhui1,Zhang Junya1,Liu Yili1,Miao Yinxing1,Liu Shaohai1,Yang Yanling1,Xu Jing‐Juan1,Ye Deju1ORCID

Affiliation:

1. State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering Chemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Nanjing 210023 China

Abstract

AbstractWe report here a tumor‐pretargted theranostic approach for multimodality imaging‐guided synergistic cancer PDT by cascade alkaline phosphatase (ALP)‐mediated in situ self‐assembly and bioorthogonal inverse electron demand Diels–Alder (IEDDA) reaction. Using the enzymatic catalysis of ALP that continuously catalyses the dephosphorylation and self‐assembly of trans‐cyclooctene (TCO)‐bearing P‐FFGd‐TCO, a high density of fluorescent and magnetic TCO‐containing nanoparticles (FMNPs‐TCO) can be synthesized and retained on the membrane of tumor cells. They can act as ‘artificial antigens’ amenable to concurrently capture lately administrated tetrazine (Tz)‐decorated PS (775NP‐Tz) and carbonic anhydrase (CA) inhibitor (SA‐Tz) via the fast IEDDA reaction. This two‐step pretargeting process can further induce FMNPs‐TCO regrowth into microparticles (FMNPs‐775/SA) directly on tumor cell membranes, which is analyzed by bio‐SEM and fluorescence imaging. Thus, efficient enrichment of both SA‐Tz and 775NP‐Tz in tumors can be achieved, allowing to alleviate hypoxia by continuously inhibiting CA activity and improving PDT of tumors. Findings show that subcutaneous HeLa tumors could be completely eradicated and no tumor recurred after irradiation with an 808 nm laser (0.33 W cm−2, 10 min). This pretargeted approach may be applied to enrich other therapeutic agents in tumors to improve targeted therapy.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Fundamental Research Funds for the Central Universities

Publisher

Wiley

Subject

General Medicine

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