With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery. A library of oligoarginine-functionalized and sharp pH-responsive polymers was synthesized and used for self-assembly with siRNA into NPs with the features of long blood circulation and pH-triggered oligoarginine-mediated endosomal membrane penetration. By further modification with ACUPA, a small molecular ligand specifically recognizing prostate-specific membrane antigen (PSMA) receptor, this envelope-type nanoplatform with multifunctional properties can efficiently target PSMA-expressing PCa cells and silence target gene expression. Systemic delivery of the siRNA NPs can efficiently silence the expression of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers, and significantly inhibit PCa tumor growth. These results suggest that this multifunctional envelope-type nanoplatform could become an effective tool for PCa-specific therapy.

Detection and quantification of biologically-relevant analytes using handheld platforms are important for point-of-care diagnostics, real-time health monitoring, and treatment monitoring. Among the various signal transduction methods used in portable biosensors, photoelectrochemcial (PEC) readout has emerged as a promising approach due to its low limit-of-detection and high sensitivity. For this readout method to be applicable to analyzing native samples, performance requirements beyond sensitivity such as specificity, stability, and ease of operation are critical. These performance requirements are governed by the properties of the photoactive materials and signal transduction mechanisms that are used in PEC biosensing. In this review, we categorize PEC biosensors into five areas based on their signal transduction strategy: (a) introduction of photoactive species, (b) generation of electron/hole donors, (c) use of steric hinderance, (d) in situ induction of light, and (e) resonance energy transfer. We discuss the combination of strengths and weaknesses that these signal transduction systems and their material building blocks offer by reviewing the recent progress in this area. Developing the appropriate PEC biosensor starts with defining the application case followed by choosing the materials and signal transduction strategies that meet the application-based specifications.

The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has led to a global pandemic with tremendous mortality, morbidity, and economic loss. The current lack of effective vaccines and treatments places tremendous value on widespread screening, early detection, and contact tracing of COVID-19 for controlling its spread and minimizing the resultant health and societal impact. Bioanalytical diagnostic technologies have played a critical role in the mitigation of the COVID-19 pandemic and will continue to be foundational in the prevention of the subsequent waves of this pandemic along with future infectious disease outbreaks. In this Review, we aim at presenting a roadmap to the bioanalytical testing of COVID-19, with a focus on the performance metrics as well as the limitations of various techniques. The state-of-the-art technologies, mostly limited to centralized laboratories, set the clinical metrics against which the emerging technologies are measured. Technologies for point-of-care and do-it-yourself testing are rapidly emerging, which open the route for testing in the community, at home, and at points-of-entry to widely screen and monitor individuals for enabling normal life despite of an infectious disease pandemic. The combination of different classes of diagnostic technologies (centralized and point-of-care and relying on multiple biomarkers) are needed for effective diagnosis, treatment selection, prognosis, patient monitoring, and epidemiological surveillance in the event of major pandemics such as COVID-19.

Development of ultrasensitive biosensors for monitoring biologically relevant analytes is the key to achieving point-of-care diagnostics and health-monitoring devices. Photoelectrochemical readout, combining photonic excitation with electrochemical readout, is envisioned to enhance the limit of detection of biosensors by increasing their sensitivity and reducing background currents generated in biological samples. In spite of this, the functionalization of photoelectrochemical transducers with biorecognition elements significantly reduces the baseline current and signal-to-background ratio of these devices. Additionally, the stability of photoactive electrodes created using photoactive nanomaterial assemblies is often insufficient for withstanding multiple washing and potential cycling steps that are involved in biosensing protocols. To overcome these challenges, we created an effective conjugation strategy for integrating TiO2 nanoparticles into photoactive electrodes. This strategy involves two components that work synergistically to increase the photoelectrochemical current of the transducers. The catechol-containing molecule, 3,4-dihydroxybenzaldehyde (DHB), is used to enhance the electronic and optical properties of TiO2 nanoparticles for signal generation. Chitosan (CHIT) is used to enhance the film-forming properties of the DHB-conjugated TiO2 nanoparticles to form uniform and stable films. Together, DHB and CHIT resulted in the formation of an extensive network of TiO2 nanoparticles within the DHB–CHIT matrix and enhanced the generated photocurrent by a factor of 10. We modified the optimized photoelectrode with DNA probes to create a photoelectrochemical DNA detector. The TiO2–DHB–CHIT photoelectrodes offered the required stability and signal magnitude to distinguish between complementary and noncomplementary DNA sequences, paving the route toward photoelectrochemical DNA sensing.