title: Targeted and pH-responsive delivery of doxorubicin to cancer cells using multifunctional dendrimer-modified multi-walled carbon nanotubes.
abstract: 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.
authors: State Key Laboratory for Modification of Chemical, Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors: Shihui
authors: S
authors: Wen
authors: Hui
authors: H
authors: Liu
authors: Hongdong
authors: H
authors: Cai
authors: Mingwu
authors: M
authors: Shen
authors: Xiangyang
authors: X
authors: Shi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D037742:Nanotubes, Carbon; C104700:PAMAM Starburst; D004317:Doxorubicin; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate
keywords: PAMAM dendrimers; doxorubicin; folic-acid targeting; multi-walled carbon nanotubes; pH-responsive delivery