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Smart pH‐Responsive Nanocarriers Based on Nano‐Graphene Oxide for Combined Chemo‐ and Photothermal Therapy Overcoming Drug Resistance
Author(s) -
Feng Liangzhu,
Li Kunyang,
Shi Xiaoze,
Gao Min,
Liu Jian,
Liu Zhuang
Publication year - 2014
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.201300549
Subject(s) - nanocarriers , doxorubicin hydrochloride , photothermal therapy , drug delivery , materials science , doxorubicin , allylamine , peg ratio , nanotechnology , biophysics , polyethylene glycol , drug , cancer cell , chemistry , pharmacology , polymer , chemotherapy , biochemistry , cancer , polyelectrolyte , medicine , biology , surgery , finance , economics , composite material
A pH‐responsive nanocarrier is developed by coating nanoscale graphene oxide (NGO) with dual types of polymers, polyethylene glycol (PEG) and poly(allylamine hydrochloride) (PAH), the latter of which is then modified with 2,3‐dimethylmaleic anhydride (DA) to acquire pH‐dependent charge reversibility. After loading with doxorubicin (DOX), a chemotherapy drug, the obtained NGO‐PEG‐DA/DOX complex exhibits a dual pH‐responsiveness, showing markedly enhanced cellular uptake under the tumor microenvironmental pH, and accelerated DOX release under a further lowered pH inside cell lysosomes. Combining such a unique behavior with subsequently slow efflux of DOX, NGO‐PEG‐DA/DOX offers remarkably improved cell killing for drug‐resistant cancer cells under the tumor microenvironmental pH in comparison with free DOX. Exploiting its excellent photothermal conversion ability, combined chemo‐ and photothermal therapy is further demonstrated using NGO‐PEG‐DA/DOX, realizing a synergistic therapeutic effect. This work presents a novel design of surface chemistry on NGO for the development of smart drug delivery systems responding to the tumor microenvironment and external physical stimulus, with the potential to overcome drug resistance.