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Research interest in nanoscale biomaterials has continued to grow in the past few decades, driving the need to form families of nanomaterials grouped by similar physical or chemical properties. Nanotubes have occupied a unique space in this field, primarily due to their high versatility in a wide range of biomedical applications. Although similar in morphology, members of this nanomaterial family widely differ in synthesis methods, mechanical and physiochemical properties, and therapeutic applications. As this field continues to develop, it is important to provide insight into novel biomaterial developments and their overall impact on current technology and therapeutics. In this review, we aim to characterize and compare two members of the nanotube family: carbon nanotubes (CNTs) and janus-base nanotubes (JBNts). While CNTs have been extensively studied for decades, JBNts provide a fresh perspective on many therapeutic modalities bound by the limitations of carbon-based nanomaterials. Herein, we characterize the morphology, synthesis, and applications of CNTs and JBNts to provide a comprehensive comparison between these nanomaterial technologies.

The blood-brain barrier (BBB) is the most specialized biological barrier in the body. This configuration of specialized cells protects the brain from invasion of molecules and particles through formation of tight junctions. To learn more about transport to the brain, in vitro modeling of the BBB is continuously advanced. The types of models and cells selected vary with the goal of each individual study, but the same validation methods, quantification of tight junctions, and permeability assays are often used. With Transwells and microfluidic devices, more information regarding formation of the BBB has been observed. Disease models have been developed to examine the effects on BBB integrity. The goal of modeling is not only to understand normal BBB physiology, but also to create treatments for diseases. This review will highlight several recent studies to show the diversity in model selection and the many applications of BBB models in in vitro research.

To realize RNA interference (RNAi) therapeutics, it is necessary to deliver therapeutic RNAs (such as small interfering RNA or siRNA) into cell cytoplasm. A major challenge of RNAi therapeutics is the endosomal entrapment of the delivered siRNA. In this study, we developed a family of delivery vehicles called Janus base nanopieces (NPs). They are rod-shaped nanoparticles formed by bundles of Janus base nanotubes (JBNTs) with RNA cargoes incorporated inside via charge interactions. JBNTs are formed by noncovalent interactions of small molecules consisting of a base component mimicking DNA bases and an amino acid side chain. NPs presented many advantages over conventional delivery materials. NPs efficiently entered cells via macropinocytosis similar to lipid nanoparticles while presenting much better endosomal escape ability than lipid nanoparticles; NPs escaped from endosomes via a “proton sponge” effect similar to cationic polymers while presenting significant lower cytotoxicity compared to polymers and lipids due to their noncovalent structures and DNA-mimicking chemistry. In a proof-of-concept experiment, we have shown that NPs are promising candidates for antiviral delivery applications, which may be used for conditions such as COVID-19 in the future.

Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as proteins, peptides, and nucleic acids. Among them, proteins have shown a series of advantages and potential in various therapeutic applications, such as introducing therapeutic proteins due to genetic defects, or used as nanocarriers for anticancer agents to decelerate tumor growth or control metastasis. This review discusses the existing nanoparticle delivery systems, introducing design strategies, advantages of using each system, and possible limitations. Moreover, we will examine the intracellular delivery of different protein therapeutics, such as antibodies, antigens, and gene editing proteins into the host cells to achieve anticancer effects and cancer vaccines. Finally, we explore the current applications of protein delivery in anticancer treatments.

Abstract RNA delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for RNA delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with small RNAs to form nano-rod delivery vehicles (termed as “Nanopieces”). Nanopieces have a diameter of ∼20nm (smallest delivery vehicles after cargo loading) and a length of ∼100nm. They present a novel breakthrough in ECM penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration.