Controlled, Stepwise Assembly of Highly Potent Drugs on Single-Wall Carbon Nanotubes

Abstract

To utilize single-wall carbon nanotubes (SWCNTs) for biomedical applications, individual dispersion and coating of SWCNTs with biocompatible molecules are important to avoid triggering cytotoxicity and increase their stability in serum-containing media. One of the common methods for producing SWCNT-based drug delivery is to individually disperse SWCNTs in aqueous solutions with various biocompatible molecules such as DNA, biopolymers, and proteins, followed by attachment of drugs and targeting moieties to the biologically dispersed nanotubes. Another approach that is less frequently used involves attaching drugs to biocompatible molecules prior to dispersing SWCNTs in a solution. Unfortunately, both approaches suffer from low SWCNT dispersion yield and lack adequate control of drug loading process, especially if the drugs are highly hydrophobic. In this talk, we present an extremely facile schema to generate SWCNT-based drug delivery systems via a controlled, stepwise assembly of drugs and biocompatible molecules on preformed SWCNT networks. We first created a three-dimensional freestanding network of SWCNTs in either aqueous or non-aqueous solvents to facilitate loading of drugs; many potent drugs are only soluble in non-aqueous solvents. SWCNTs in freestanding networks were then coated with drugs such as doxorubicin, which is a common model drug used for characterization of drug loading and release processes owing to its optical properties, and paclitaxel, which is a model drug representing highly lipophilic drugs. Drug-coated SWCNT networks were coated with proteins, such as albumins, followed by dispersing in water via gentle sonication with almost no loss of SWCNT dispersion yield. Optical characterization and imaging have shown that SWCNTs/drug/protein complexes are highly individualized in solution and readily internalized by cells upon exposure. The loaded drugs were efficiently released upon internalization and displayed larger reduction in cell viability compared to free drugs. Further, to demonstrate robustness of our approach and to assist with drug release, we coated SWCNTs with biocompatible polymers prior to decorating with drugs to serve as a sacrificial yet assistive layer. The polymer coating did not alter SWCNT dispersion and drug loading significantly and allowed for faster release of drugs upon internalization in the cells. Overall, the proposed method allows for precisely controlled, stepwise assembly of SWCNTs with any drug and biomolecule combinations and could be further developed for multifunctional drug delivery platform utilizing SWCNTs.