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Tumor‐Oriented Telomerase‐Terminated Nanoplatform as Versatile Strategy for Multidrug Resistance Reversal in Cancer Treatment
Author(s) -
Wu Yahui,
Zhong Dan,
Li Yachao,
Wu Huayu,
Xu Xianghui,
Yang Jun,
Gu Zhongwei
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201901739
Subject(s) - telomerase , multiple drug resistance , doxorubicin , telomerase reverse transcriptase , apoptosis , prodrug , cancer cell , microvesicles , drug delivery , cancer research , drug resistance , chemistry , intracellular , cancer , biology , materials science , nanotechnology , biochemistry , chemotherapy , microrna , genetics , microbiology and biotechnology , gene
Multidrug resistance is one of the major problems in chemotherapy, and exploiting impactful targets to reverse drug resistance of most tumors remains a difficult problem. In this study, the tumor‐oriented nanoparticle, BIBR1532‐loaded peptide dendrimeric prodrug nanoassembly (B‐PDPN), is used to assist telomerase inhibition for multidrug resistance reversal. B‐PDPN possesses the characteristics of an acid‐activated histidine to promote cellular uptake, a redox‐sensitive poly(ethylene glycol) (PEG) layer to actualize endosomal escape and telomerase inhibitor release, and an acid sensitive chemical bond to facilitate chemotherapeutic drug release. Telomerase termination weakens the protective effect of hTERT protein on mitochondria and enhances reactive oxygen species (ROS) production, which increases DNA damage and apoptosis. The tumor‐oriented nanoparticle B‐PDPN achieves a broad‐spectrum telomerase inhibition to combat multidrug resistance. In vivo experiments support the evidence that B‐PDPN accumulates in the tumor site and reduces the expression of hTERT in tumor tissues to inhibit drug resistant tumor growth. This work introduces an innovative strategy of utilizing features of tumor‐activated nanoplatform to assist telomerase termination. The nanoplatform enhances intracellular drug concentration and nucleus delivery of doxorubicin (DOX), and promotes DNA damage to combat multidrug resistance.