Directed Graphene‐Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance

Abstract

Multidrug resistance (MDR), which leads tumors resistance to traditional anticancer drugs, can cause the failure of chemotherapy treatments. Herein, we present a new way to overcome this problem using smart multifunctional graphene‐based drug delivery systems which can target subcellular organelles and show synergistic hyperthermia and chemotherapy. Mitochondria‐targeting ligands are conjugated onto the doxorubicin‐loaded, polyglycerol‐covered nanographene sheets to actively accumulate them inside the mitochondria after charge‐mediated cellular internalization. Upon near‐infrared (NIR) irradiation, adenosine triphosphate (ATP) synthesis and mitochondrial function were inhibited and doxorubicin released into the cellular interior. The hyperthermia‐accelerated drug release led to a highly selective anticancer efficiency, confirmed by in vitro and in vivo experiments.

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

“…[ 35 ] hPG with 10% amino functional groups (hPG(NH 2 ) 10% ) was prepared via an azido substitution and reduction procedure from hPG. [ 15 ] Then, the hPG(NH 2 ) 10% was conjugated onto nGO via an amidation reaction with 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) as condensing agent in 2‐( N ‐morpholino)ethanesulfonic acid solution (MES) to obtain hPG‐covered nGO (GOP). [ 15 ] Afterward, (bicyclo[6.1.0]non‐4‐yn‐9‐yl)methyl 4‐nitrophenyl carbonate (BCN) was applied to modify GOP with cyclooctyne moieties to produce GOP BCN .…”

“…[ 15 ] Then, the hPG(NH 2 ) 10% was conjugated onto nGO via an amidation reaction with 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) as condensing agent in 2‐( N ‐morpholino)ethanesulfonic acid solution (MES) to obtain hPG‐covered nGO (GOP). [ 15 ] Afterward, (bicyclo[6.1.0]non‐4‐yn‐9‐yl)methyl 4‐nitrophenyl carbonate (BCN) was applied to modify GOP with cyclooctyne moieties to produce GOP BCN . [ 42 ] The reaction between thiol group of cR 10 peptide and cyclooctyne moieties of GOP BCN in PBS resulted in nanoplatforms with the peptide functionality (GOPR) ( Scheme ).…”

“…[ 7–13 ] Although many graphene‐based antitumor systems have been constructed and much progress has been achieved in this field, the situation becomes more complicated and challenging when it meets the multidrug resistance (MDR). [ 14,15 ] The emergence of MDR is largely owing to the overexpression of ATP‐binding cassette, in particular, P‐glycoprotein (P‐gP), on the plasma membrane. [ 14–16 ] These proteins reduce the internalization of therapeutic agents into the cells and even mediate the efflux of these agents from the cells.…”

“…[ 14,15 ] The emergence of MDR is largely owing to the overexpression of ATP‐binding cassette, in particular, P‐glycoprotein (P‐gP), on the plasma membrane. [ 14–16 ] These proteins reduce the internalization of therapeutic agents into the cells and even mediate the efflux of these agents from the cells. In recent years, a variety of functional nanomaterials and smart nanodevices were developed to incapacitate P‐gP and to deliver anticancer drugs across the plasma membrane.…”

“…[ 16,17 ] Despite the efficient cellular uptake and improved drug concentration inside the cytoplasm of cancer cells, the “efflux pump” still frustrates the chemotherapy. [ 14–16 ] This shortage is more serious when it comes to therapeutic agents with specific targeting organelles, such as doxorubicin (DOX), whose anticancer mechanism is to intercalate with DNA in the nucleus. [ 18,19 ] Therefore, efficient tumor therapy could hardly be achieved if MDR is not efficiently suppressed and therapeutic agents are not localized into the target organelles.…”