Single-walled carbon nanotubes (SWCNTs) have been used in a variety of sensing and imaging applications over the past few years due to their unique optical properties. In the solution phase, SWCNTs are employed as near-infrared (NIR) fluorescence-based sensors of target analytes via modulations in emission intensity and/or wavelength. In an effort to lower the limit of detection, research has been conducted into isolating SWCNTs adhered to surfaces for potential single molecule analyte detection. However, it is known that SWCNT fluorescence is adversely affected by the inherently rough surfaces that are conventionally used for their observation (e.g., glass coverslip), potentially interfering with fluorescence-based analyte detection. Here, using a spin-coating method with thin films of alginate and SWCNTs, we demonstrate that a novel hydrogel platform can be created to investigate immobilized individual SWCNTs without significantly perturbing their optical properties as compared to solution-phase values. In contrast to the glass coverslip, which red-shifted DNA-functionalized (6,5)-SWCNTs by an average of 3.4 nm, the hydrogel platform reported emission wavelengths that statistically matched the solution-phase values. Additionally, the heterogeneity in the wavelength measurements, as determined from the width of created histograms, was reduced nearly by a factor of 3 for the SWCNTs in the hydrogel platform when compared to glass coverslips. Using long SWCNTs, i.e., those with an average length above the diffraction limit of our microscope, we show that a glass coverslip can induce optical heterogeneity along the length of a single SWCNT regardless of its surface functionalization. This is again significantly mitigated when examining the long SWCNTs in the hydrogel platform. Finally, we show that upon the addition of a model analyte (calcium chloride), the optical response can be spatially resolved along the length of a single SWCNT, enabling localized analyte detection on the surface of a single nanoscale sensor.

Pulsatile chemotherapeutic delivery profiles may provide a number advantages by maximizing the anticancer toxicity of chemotherapeutics, reducing off-target side effects, and combating adaptive resistance. While these temporally dynamic deliveries have shown some promise, they have yet to be clinically deployed from implantable hydrogels, whose localized deliveries could further enhance therapeutic outcomes. Here, several pulsatile chemotherapeutic delivery profiles were tested on melanoma cell survival in vitro and compared to constant (flatline) delivery profiles of the same integrated dose. Results indicated that pulsatile delivery profiles were more efficient at killing melanoma cells than flatline deliveries. Furthermore, results suggested that parameters like the duration of drug “on” periods (pulse width), delivery rates during those periods (pulse heights), and the number/frequency of pulses could be used to optimize delivery profiles. Optimization of pulsatile profiles at tumor sites in vivo would require hydrogel materials capable of producing a wide variety of pulsatile profiles (e.g., of different pulse heights, pulse widths, and pulse numbers). This work goes on to demonstrate that magnetically responsive, biphasic ferrogels are capable of producing pulsatile mitoxantrone delivery profiles similar to those tested in vitro. Pulse parameters such as the timing and rate of delivery during “on” periods could be remotely regulated through the use of simple, hand-held magnets. The timing of pulses was controlled simply by deciding when and for how long to magnetically stimulate. The rate of release during pulse “on” periods was a function of the magnetic stimulation frequency. These findings add to the growing evidence that pulsatile chemotherapeutic delivery profiles may be therapeutically beneficial and suggest that magnetically responsive hydrogels could provide useful tools for optimizing and clinically deploying pulsatile chemotherapeutic delivery profiles.

Externally controllable drug delivery systems are crucial for a variety of biological applications where the dosage and timing of drug delivery need to be adjusted based on disease diagnosis and progression. Here, we have developed an externally controllable drug delivery system by combining three extensively used platforms: hydrogels, liposomes, and single-walled carbon nanotubes (SWCNTs). We have developed carbon nanotube–liposome complexes (CLCs) and incorporated these structures into a 3D alginate hydrogel for use as an optically controlled drug delivery system. The CLC structures were characterized by using a variety of imaging and spectroscopic techniques, and an optimal SWCNT/lipid ratio was selected. The optimal CLCs were loaded with a model drug (FITC-Dex), incorporated into a hydrogel, and their release profile was studied. It was shown that release of the drug cargo can be triggered by using an NIR laser stimulation tuned to the optical resonance of a particular SWCNT species. It was further shown that the amount of released cargo can be tuned by varying the NIR stimulation time. This system demonstrates the externally controlled delivery of drug cargo and can be used for different applications including cancer chemotherapy delivery.

The sequence and timing of growth factor delivery plays a crucial role in bone regeneration. While a variety of biomaterial scaffolds have been developed to provide multiple growth factor deliveries, there still exists a strong need for ondemand control over sequential delivery profiles to optimize regenerative outcomes. One particular growth factor, bone morphogenetic protein-2 (BMP-2), has established effects in the osteodifferentiation process; however, the optimal timing of its delivery is not yet known. Here, we investigate the effect of the timing of BMP-2 delivery on osteodifferentiation on both 2D and 3D cell cultures in vitro. It was shown that immediate BMP-2 delivery inhibited mouse mesenchymal stem cell (mMSC) proliferation and therefore resulted in suboptimal levels of mMSC osteodifferentiation (as measured by alkaline phosphatase activity) compared to mMSC cultures exposed to delayed BMP-2 delivery (4 day delay). Because of this, we aimed to develop a biomaterial system capable of rapidly recruiting mMSCs and exposing them to BMP-2 in a delayed manner (i.e., after a strong mMSC population has been established). This biomaterial system consisted of (i) an outer porous gelatin compartment that could be loaded with an mMSC recruitment factor (stromal cell-derived factor 1-α (SDF-1α)) for rapid establishment of a 3D mMSC culture and (ii) an inner ferrogel compartment that could deliver BMP-2 in an immediate or delayed manner, depending on when magnetic stimulation was applied. It was shown that the outer compartment was able to recruit and harbor mMSCs and that the rapidity of this recruitment could be enhanced by loading the compartment with SDF-1α. The inner ferrogel compartment enabled magnetically triggered release of BMP-2 where the timing of release could be remotely controlled from immediate to a delay of up to 11 days. This hydrogel system provides controllability over the timing between bone progenitor recruitment and osteodifferentiation factor release and can thus potentially enhance therapies that require new bone growth by optimizing the timing of these deliveries.