Graphene Oxide‐Cyclic R10 Peptide Nuclear Translocation Nanoplatforms for the Surmounting of Multiple‐Drug Resistance

Abstract

Multidrug resistance resulting from a variety of defensive pathways in cancer has become a global concern with a considerable impact on the mortality associated with the failure of traditional chemotherapy. Therefore, further research and new therapies are required to overcome this challenge. In this work, a cyclic R10 peptide (cR10) is conjugated to polyglycerol‐covered nanographene oxide to engineer a nanoplatform for the surmounting of multidrug resistance. The nuclear translocation of the nanoplatform, facilitated by cR10 peptide, and subsequently, a laser‐triggered release of the loaded doxorubicin result in efficient anticancer activity confirmed by both in vitro and in vivo experiments. The synthesized nanoplatform with a combination of different features, including active nucleus‐targeting, high‐loading capacity, controlled release of cargo, and photothermal property, provides a new strategy for circumventing multidrug resistant cancers.

Recent Progress of Novel Nanotechnology Challenging the Multidrug Resistance of Cancer

“…The nuclear translocation of this nanomedicine was facilitated by the cR(10) peptide. Subsequently, a laser-triggered release of the loaded DOX results in efficient anticancer activity confirmed by both in vitro and in vivo experiments ( Tu et al, 2020 ). The biodistribution and photothermal effects of this nanomedicine were studied in HeLa-R tumor-bearing nude mice.…”

“…The nucleus has been proved to be the main interaction site of most therapeutics. Therefore, it is highly expected that nuclear targeted NDDSs can provide a more effective strategy than ordinary cell membrane-targeted therapy (Wang et al, 2011;Ling et al, 2012;Li et al, 2018;Li H. et al, 2019;Tu et al, 2020). Tu,Z.…”

“…The nucleus has been proved to be the main interaction site of most therapeutics. Therefore, it is highly expected that nuclear targeted NDDSs can provide a more effective strategy than ordinary cell membrane-targeted therapy ( Wang et al, 2011 ; Ling et al, 2012 ; Li et al, 2018 ; Li H. et al, 2019 ; Tu et al, 2020 ). Tu, Z. et al conjugated a cyclic R10 peptide [cR(10)] to polyglycerol-covered nanographene oxide for developing a novel nanomedicine to overcome multidrug resistance.…”

Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes

“…The nanoplatform designed to overcome multidrug resistance consisting of R10 peptide conjugated to polyglycerol-covered nanoscale GO exhibited easier nuclear translocation due to R10 peptide; a laser-triggered release of the loaded DOX showed superb anticancer activity in vitro as well as in experiments performed in vivo. This nanoplatform was characterized with a high-loading capacity, controlled release of drugs, and photothermal properties [ 226 ]. NPs consisting of functional GO conjugated with PEG, FA and indocyanine green acting as photosensitizer fabricated for delivery of MutT homolog 1 (MTH1) inhibitor (6-(2,3-dichlorophenyl)- N 4 -methylpyrimidine- 2,4-diamine hydrochloride; TH287) and DOX applied in combined chemo-photodynamic therapy, inhibited the proliferation and migration of osteosarcoma cells, stimulated both apoptosis and autophagy by suppressing the MTH1 protein and enhanced ROS accumulation.…”

Co‐Delivery of Doxorubicin and Chloroquine by Polyglycerol Functionalized MoS2 Nanosheets for Efficient Multidrug‐Resistant Cancer Therapy

“…Hyperbranched polyglycerol (hPG) as a highly functional and water‐soluble polymer has been used for the modification of 2D carbon nanomaterials. [ 26–32 ] Modifying MoS 2 with hPG can improve its functionality, biocompatibility and water dispersibility. Wang et al have shown that modification of MoS 2 via physical adsorption of hPG improves the physicochemical properties of this material.…”