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Targeted and pH‐Responsive Delivery of Doxorubicin to Cancer Cells Using Multifunctional Dendrimer‐Modified Multi‐Walled Carbon Nanotubes
Author(s) -
Wen Shihui,
Liu Hui,
Cai Hongdong,
Shen Mingwu,
Shi Xiangyang
Publication year - 2013
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.201200389
Subject(s) - dendrimer , amidoamine , doxorubicin , poly(amidoamine) , cancer cell , drug delivery , fluorescein isothiocyanate , chemistry , carbon nanotube , covalent bond , materials science , biophysics , combinatorial chemistry , nanotechnology , biochemistry , cancer , fluorescence , organic chemistry , chemotherapy , medicine , physics , surgery , quantum mechanics , biology
We report the use of multifunctional dendrimer‐modified multi‐walled carbon nanotubes (MWCNTs) for targeted and pH‐responsive delivery of doxorubicin (DOX) into cancer cells. In this study, amine‐terminated generation 5 poly(amidoamine) (PAMAM) dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) were covalently linked to acid‐treated MWCNTs, followed by acetylation of the remaining dendrimer terminal amines to neutralize the positive surface potential. The formed multifunctional MWCNTs (MWCNT/G5.NHAc‐FI‐FA) were characterized via different techniques. Then, the MWCNT/G5.NHAc‐FI‐FA was used to load DOX for targeted and pH‐responsive delivery to cancer cells overexpressing high‐affinity folic acid receptors (FAR). We showed that the MWCNT/G5.NHAc‐FI‐FA enabled a high drug payload and encapsulation efficiency both up to 97.8% and the formed DOX/MWCNT/G5.NHAc‐FI‐FA complexes displayed a pH‐responsive release property with fast DOX release under acidic environment and slow release at physiological pH conditions. Importantly, the DOX/MWCNT/G5.NHAc‐FI‐FA complexes displayed effective therapeutic efficacy, similar to that of free DOX, and were able to target to cancer cells overexpressing high‐affinity FAR and effectively inhibit the growth of the cancer cells. The synthesized multifunctional dendrimer‐modified MWCNTs may be used as a targeted and pH‐responsive delivery system for targeting therapy of different types of cancer cells.

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