Intratumoral delivery of immune therapy and gene therapy: the next era for cancer therapy.

Cancer immunotherapy is a field that garners significant interest, fueled by the clinical success of immune checkpoint inhibitors. In contrast to conventional cancer therapies, immunotherapies leverage the host's immune system by enhancing innate and adaptive immunity to control cancer progression. Despite these exciting advances, only a subset of patients respond to these drugs, and immunotherapies frequently result in immune-related toxicity. One approach to overcome these challenges is intratumoral administration of treatment to minimize systemic toxicities and maximize therapeutic effects. Intratumoral cancer therapies have shown similar or superior antitumor efficacy in both treated and distant untreated tumors, with a widely improved benefit-risk ratio over conventional therapeutic approaches. Herein, we review the current landscape of intratumoral cancer gene immunotherapy.

Immunotherapies are drugs designed to activate a patient's own immune system to fight cancer. Research in this field has soared following the US FDA's approval of the first class of these drugs. They work by blocking cancer cells' ability to hide from the body's immune system. Unfortunately, only some patients respond and many experience side effects when the medicine is delivered to the whole body. One approach to overcome these problems is to deliver these drugs directly into a patient's tumor to limit side effects while maintaining the positive effects. In this review we describe the benefits of giving these types of drugs directly into tumors over whole-body administration. We summarize the current clinical data and explain the mechanisms behind each drug.

A flexible adhesive surface electrode array capable of cervical electroneurography during a sequential autonomic stress challenge.

This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.

Smart Electronic Eyedrop Bottle for Unobtrusive Monitoring of Glaucoma Medication Adherence.

Glaucoma, the leading cause of irreversible blindness, affects >70 million people worldwide. Lowering intraocular pressure via topical administration of eye drops is the most common first-line therapy for glaucoma. This treatment paradigm has notoriously high non-adherence rates: ranging from 30% to 80%. The advent of smart phone enabled technologies creates promise for improving eyedrop adherence. However, previous eyedrop electronic monitoring solutions had awkward medication bottle adjuncts and crude software for monitoring the administration of a drop that adversely affected their ability to foster sustainable improvements in adherence. The current work begins to address this unmet need for wireless technology by creating a "smart drop" bottle. This medication bottle is instrumented with sensing electronics that enable detection of each eyedrop administered while maintaining the shape and size of the bottle. This is achieved by a thin electronic force sensor wrapped around the bottle and underneath the label, interfaced with a thin electronic circuit underneath the bottle that allows for detection and wireless transmission to a smart-phone application. We demonstrate 100% success rate of wireless communication over 75 feet with <1% false positive and false negative rates of single drop deliveries, thus providing a viable solution for eyedrop monitoring for glaucoma patients.

Electrochemical Surface Treatment of Discontinuous Carbon Fibers.

We developed an operationally simple electrolytic design for the surface treatment of short carbon fibers. Using X-ray photoelectron spectroscopy (XPS), we demonstrated that the electrochemical surface treatment of discontinuous fibers is highly reproducible, uniform, and tunable. Specifically, total amounts of surface oxygen and nitrogen contents (0 to 17 atomic %) as well as surface oxygen-to-nitrogen ratio (1:0 to 1:2) vary significantly over the ranges of each processing parameter: applied voltage (1.5-21 V), location of carbon fiber (i.e., anode, cathode, or mixed mode), initial temperature (3-70.5 °C), and ammonium bicarbonate concentration (0.005-0.75 M). Optimized processing conditions afforded carbon fibers that have similar surface compositions (86.3 ± 1.1 at. % C, 8.9 ± 0.8 at. % O, 4.7 ± 0.6 at. % N) as those of commercially available continuous fibers. In addition, these fibers retain their mechanical properties (tensile strength and tensile modulus) and exhibit no detectable surface damage based on single fiber tensile tests and scanning electron microscopy (SEM). We also performed a number of control experiments to develop a proposed mechanism for the surface functionalization of the carbon fiber. These mechanistic studies demonstrated that water splitting contributes significantly to the oxidation of carbon fibers and that other species in the chemical equilibria of ammonium bicarbonate (and not just its individual ions) play a significant role in functionalizing carbon fiber surfaces.