Krum, D. | Search bioRxiv

bioRxiv2026

Engineering hyaluronic acid-binding cytokines for enhanced tumor retention and safety

Intratumoral delivery of immunotherapy offers a means to enhance efficacy while limiting systemic toxicity, yet rapid diffusion from the tumor constrains dosing levels. Extracellular matrix-targeted anchoring strategies have emerged to improve tumor retention, but the influence of matrix target choice remains poorly understood. Here, we engineered a hyaluronic acid-anchoring platform and directly compared it to a well-established collagen-binding strategy for the delivery of IL-12/IL-15 combination therapy, assessing pharmacokinetic, efficacy, and toxicity endpoints. Hyaluronic acid anchoring markedly enhanced intratumoral retention and tumor loading relative to both unanchored and collagen-anchored constructs. While all anchored cytokine therapies achieved comparable curative tumor control, hyaluronic acid anchoring was associated with improved tolerability, including attenuated systemic inflammation, reduced liver toxicity, and diminished local tissue damage. Analysis of intratumoral immune signaling further indicated that the anchoring strategy modulates local cytokine exposure and immune cell infiltration, despite similar therapeutic outcomes. These findings demonstrate that extracellular matrix target selection significantly shapes the pharmacologic and safety profiles of intratumoral biologics, and identify hyaluronic acid anchoring as an alternative retention strategy with potential advantages.

bioengineering↗

bioRxiv2019

Embodiment improves performance on an immersive brain computer interface in head-mounted virtual reality

Brain computer interfaces (BCI) can be used to provide individuals with neurofeedback of their own brain activity and train them to learn how to control their brain activity. Neurofeedback-based BCIs used for motor rehabilitation aim to close the loop between attempted motor commands and sensory feedback by providing supplemental sensory information when individuals successfully establish specific brain patterns. Existing neurofeedback-based BCIs have used a variety of displays to provide feedback, ranging from devices that provide a more immersive and compelling experience (e.g., head-mounted virtual reality (HMD-VR) or CAVE systems) to devices that are considered less immersive (e.g., computer screens). However, it is not clear whether more immersive systems (i.e., HMD-VR) improve neurofeedback performance compared to computer screens, and whether there are individual performance differences in HMD-VR versus screen-based neurofeedback. In this pilot experiment, we compared neurofeedback performance in HMD-VR versus on a computer screen in twelve healthy individuals. We also examined whether individual differences in presence or embodiment correlated with neurofeedback performance in either environment. Participants were asked to control a virtual right arm by imagining right hand movements. Real-time brain activity indicating motor imagery, which was measured via electroencephalography (EEG) as desynchronized sensorimotor rhythms (SMR; 8-24 Hz) in the left motor cortex, drove the movement of the virtual arm towards (increased SMR desynchronization) or away from (decreased SMR desynchronization) targets. Participants performed two blocks of 30 trials, one for each condition (Screen, HMD-VR), with the order of conditions counterbalanced across participants. After completing each block, participants were asked questions relating to their sense of presence and embodiment in each environment. We found that, while participants performance on the neurofeedback-based BCI task was similar between conditions, the participants reported levels of embodiment was significantly different between conditions. Specifically, participants experienced higher levels of embodiment in HMD-VR compared to the computer screen. We further found that reported levels of embodiment positively correlated with neurofeedback performance only in the HMD-VR condition. Overall, these preliminary results suggest that embodiment may improve performance on a neurofeedback-based BCI and that HMD-VR may increase embodiment during a neurofeedback-based BCI task compared to a standard computer screen.

neuroscience↗