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Rational design of a triple tumor microenvironment-responsive nanoplatform for enhanced tumor theranostics

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Liu,  Yuxin       
Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Zitation

Zhang, S., Han, X., Chen, X., Liu, Y., & Zhou, J. (2023). Rational design of a triple tumor microenvironment-responsive nanoplatform for enhanced tumor theranostics. Chemistry – A European Journal, 29(7): e202202469. doi:10.1002/chem.202202469.


Zitierlink: https://hdl.handle.net/21.11116/0000-000B-4878-E
Zusammenfassung
The development of responsive nanoplatforms based on the tumor microenvironment (TME) is critical for tumor diagnosis and treatment. Concentrating on a single TME-responsive nanoplatform, however, may result in insufficient diagnostic accuracy and treatment efficacy. Herein, layered double-hydroxides (LDHs) and rare earth nanomaterials (Er@Lu) were combined to create a triple TME-responsive nanoplatform that was then modified with cypate (a fluorescent dye with strong absorbance) by a peptide chain and loaded with epigallocatechin gallate (EGCG), a chemotherapeutic drug. Multiple responses to TME occurred when Er@Lu/LDH-EGCG reached the colorectal tumor region. Based on an acidic TME, the nanoplatform cracked and released Ni2+ and EGCG. NiS, which was produced by the reaction of Ni2+ with abundant H2S in tumor cells, was used for photothermal therapy and the released EGCG was used for chemotherapy. The MMP-7 enzyme specifically expressed in tumor cells recognized and cut the peptide chain, resulting in cypate release. The fluorescence of the Er@Lu was then restored along with the release of cypate because of the absorption competition disappearance. Compared to a single TME response, Er@Lu/LDH-EGCG with a triple TME response led to a better synergistic therapeutic effect in vitro and in vivo . This work has provided new approaches for developing multiple TME-responsive therapeutic nanoplatforms for synergistic therapy with improved diagnosis and therapeutic efficiency.