Tumor‐Oriented Telomerase‐Terminated Nanoplatform as Versatile Strategy for Multidrug Resistance Reversal in Cancer Treatment

Abstract

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.

Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy

“…Polyethylene glycol (PEG) is one of the most widely used hydrophilic polymer approved by FDA with negligible toxicity and low immunogenicity, which has been expected to effectively reduce the non-specific uptake by the reticuloendothelial system (RES), prolong circulation time and allow for specific tumortargeting via the enhanced permeability and retention (EPR) effect (20)(21)(22)(23)(24). Thus, PEGylated doxorubicin prodrugs have shown distinctly therapeutic advantages including better antitumor activity and fewer side effects than free drugs.…”

Recent Progress of Novel Nanotechnology Challenging the Multidrug Resistance of Cancer

“…The inhibition of telomerase can effectively increase the chemosensitivity of tumor cells. Therefore, the construction of new NDDS-targeting telomerase has also achieved an obvious therapeutic effect on multidrug-resistant tumors ( Wu Y. et al, 2020 ).…”

What the Microscale Systems “See” In Biological Assemblies: Cells and Viruses?

“…This approach provided an efficient platform for evaluating nitric oxide production related to several cardiovascular disorders and neurodegenerative diseases. Because telomerase is a common tumor disease marker and a new target for cancer treatment, the telomerase assay is important for the early diagnosis and therapy of cancer. , To achieve ultrasensitive telomerase detection at a single-cell level, an MCE–CL platform depending on T7 exonuclease-assisted signal amplification was developed . Because of the application of MCE, the substrate interference could be reduced, and high-throughput detection was achieved.…”