(Invited) Step-Wise Molecular Self-Assembly on Single-Wall Carbon Nanotube Networks: Towards Development of Delivery Systems of Highly Potent but Difficult to Administer Drugs

Abstract

Single-walled carbon nanotubes (SWCNTs) are increasingly being investigated for biomedical imaging, sensing, and drug delivery. Individual dispersion and coating with biocompatible molecules of SWCNTs are essential to avoid triggering cytotoxicity and to realize these applications. Perhaps the most common method for generating SWCNT-based drug delivery systems involves individually dispersing SWCNTs in water with various biocompatible molecules such as DNA, biopolymers and proteins followed by linking drugs and targeting moieties to the biocompatible coating. Another relatively less frequently exploited approach entails first attaching drugs to SWCNTs and then dispersing with biocompatible molecules, which may also be targetable. Unfortunately, both approaches suffer from low SWCNT dispersion yield and inadequate control of drug loading process, particularly if the drugs are highly potent and difficult to administer. We have developed an extremely facile scheme to generate SWCNT-based drug delivery systems by controllably depositing biocompatible molecules and drugs on preformed SWCNT hydrogels. We first individually dispersed SWCNTs in water using suitable surfactant molecules, concentrated the dispersion to form freestanding hydrogels, and then removed the surfactant from the hydrogel. These surfactant-free SWCNT hydrogels comprise of three-dimensional, isotropic network of individual nanotubes held together via van der Waals interactions the junctions between nanotubes, and have >99% porosity, which allows unimpeded transport of biocompatible molecules and drugs. Furthermore, since many potent drugs are only soluble in non-aqueous solvents, water in the hydrogel can be easily exchanged with other suitable solvents to facilitate drug loading. As a proof-of-concept, we coated SWCNTs within the hydrogels first with drugs such as Doxorubicin, Bleomycin, and Digoxin, then with proteins such as albumins, and lastly dispersed in water through gentle 5 minutes sonication with little or no loss of SWCNT yield. Optical characterizations and imaging show that the albumin/drug/SWCNTs complexes are individually dispersed that the cells readily uptake. To demonstrate robustness of this approach, we coated SWCNTs with polymers prior to decorating with biomolecules/drug layers; the polymer coating was chosen to assist in rapid drug release after cell uptake. Overall, this approach allows precisely controlled, step-wise molecular self-assembly on SWCNTs of any drug and biomolecule combinations, suggesting high potential for development of multifunctional drug delivery platforms utilizing SWCNTs.