Drug-loading capacity and nuclear targeting of multiwalled carbon nanotubes grafted with anionic amphiphilic copolymers
Hsieh-Chih Tsai,1,* Jeng-Yee Lin,2,* Faiza Maryani,1 Chun-Chiang Huang,1 Toyoko Imae1,3
1Graduate Institute of Applied Science and Technology, 2Division of Plastic Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, 3Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan
*These authors contributed equally to this work
Abstract: In this study, three types of hybrid nanotubes (NTs), ie, oxidized multiwalled carbon NTs (COOH MWCNTs), heparin (Hep)-conjugated MWCNTs (Hep MWCNTs), and diblock copolymer polyglycolic acid (PGA)-co-heparin conjugated to MWCNTs (PGA MWCNTs), were synthesized with improved biocompatibility and drug-loading capacity. Hydrophilic Hep substituents on MWCNTs improved biocompatibility and acted as nucleus-sensitive segments on the CNT carrier, whereas the addition of PGA enhanced drug-loading capacity. In the PGA MWCNT system, the amphiphilic copolymer (PGA-Hep) formed micelles on the side walls of CNTs, as confirmed by electron microscopy. The PGA system encapsulated the hydrophobic drug with high efficiency compared to the COOH MWCNT and Hep MWCNT systems. This is because the drug was loaded onto the PGA MWCNTs through hydrophobic forces and onto the CNTs by ∏–∏ stacking interactions. Additionally, most of the current drug-carrier designs that target cancer cells release the drug in the lysosome or cytoplasm. However, nuclear-targeted drug release is expected to kill cancer cells more directly and efficiently. In our study, PGA MWCNT carriers effectively delivered the active anticancer drug doxorubicin into targeted nuclei. This study may provide an effective strategy for the development of carbon-based drug carriers for nuclear-targeted drug delivery.
Keywords: carbon nanotube, amphiphilic copolymer, drug loading, nucleus targeting, cancer therapy
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