Covalent organic frameworks (COFs) are an emerging class of organic crystalline polymers with welldefined molecular geometry and tunable porosity. COFs are formed via reversible condensation of lightweight molecular building blocks which dictate its geometry in two or three dimensions. Among COFs, two-dimensional COFs (2D COFs) have garnered special attention due to their unique structure composed of two-dimensionally extended organic sheets stacked in layers generating periodic columnar π-arrays, functional pore space and their ease of synthesis. These unique features in combination with their low density, high crystallinity, large surface area, and biodegradability have made them an excellent candidate for a plethora of applications ranging from energy to biomedical sciences. In this article, the evolution of 2D COFs is briefly discussed in terms of different types of chemical linkages, synthetic strategies of bulk and nanoscale 2D COFs, and their tunability from a biomedical perspective. Next, the recent advances of these 2D nanomaterials in biomedicine and biotechnology are summarized emphasizing the principles and strategies involved. In addition, current challenges and emerging approaches of 2D COFs for the advanced biomedical applications are discussed.

Despite the significant advances in neurology, the cure for neurodegenerative conditions remains a formidable task to date. Among various factors arising from the complex etiology of neurodegenerative diseases, neuroinflammation and oxidative stress play a major role in pathogenesis. To this end, some phytocannabinoids isolated from Cannabis sativa (widely known as marijuana) have attracted significant attention as potential neurotherapeutics. The profound effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has led to the discovery of the endocannabinoid system as a molecular target in the central nervous system (CNS). Cannabidiol (CBD), the major non-psychoactive component of cannabis, has recently emerged as a potential prototype for neuroprotective drug development due to its antioxidant and anti-inflammatory properties and its well-tolerated pharmacological behavior. This review briefly discusses the role of inflammation and oxidative stress in neurodegeneration and demonstrates the neuroprotective effect of cannabidiol, highlighting its general mechanism of action and disease-specific pathways in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Furthermore, we have summarized the preclinical and clinical findings on the therapeutic promise of CBD in PD and AD, shed light on the importance of determining its therapeutic window, and provide insights into identifying promising new research directions.

Despite significant progress in neurosurgery and radiation therapy during the past decade, overall survivability (OS) of glioblastoma patients continues to be less than 2 years. The scope of systemic chemotherapy is greatly limited by poor drug transport across the blood brain barrier (BBB) and, thereby, suboptimal drug accumulation in glioma tissue. To this end, use of large amino acid transporter-1 (LAT1) overexpressed both on brain capillary endothelial cells (BCECs) and glioma cells has begun. Prior reports on the use of LAT1 mediated delivery of model drugs showed their brain accumulations. However, in depth in vivo glioblastoma regression studies aimed at examining the therapeutic potential of LAT1 mediated delivery of potent chemotherapeutics to brain tumor tissues have not yet been undertaken. Herein, we report on the development of a nanometric (100-135 nm) promising LAT1 selective liposomal drug carrier prepared from a novel l-3,4-dihydroxyphenylalanine (l-DOPA) functionalized amphiphile (Amphi-DOPA). In vitro studies using Rh-PE labeled liposomes of Amphi-DOPA both in untreated glioma (GL261) cells and in GL261cells preincubated with LAT1 antibody revealed LAT1 mediated cellular uptake. Intravenously administered NIR-dye labeled liposomes of Amphi-DOPA in glioblastoma-bearing mice showed preferential accumulation of the dye in brain tissue. Notably iv administration of WP1066-loaded liposomes of Amphi-DOPA enhanced the overall survivability of C57BL/6J mice bearing orthotopically established mouse glioblastoma by ∼60% compared to that for the untreated mouse group. Furthermore, we show that the OS of established glioblastoma-bearing mice can be significantly enhanced (by >300% compared to that for the untreated mouse group) when the presently described LAT1 mediated targeted chemotherapy with WP1066-loaded liposomes of Amphi-DOPA is combined with in vivo DC-targeted DNA vaccination using a survivin (a glioblastoma antigen) encoded DNA vaccine. The present findings open a new door for LAT1 mediated systemic chemotherapy of glioblastoma.

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Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mechanical properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mechanical deformation. The chemically cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high conductivity, compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mechanical, electronic, and biological characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.

Limited tumor tissue penetration is one of the key impeding factors retarding successful in vivo exploitations of anti-angiogenic cancer therapy. Herein we report on the design of a cell penetrating peptide-decorated lipid nano-assembly which, upon systemic administration, induces significant mouse tumor growth inhibition via enhanced tumor infiltration of encapsulated anti-angiogenic siRNA.

Two‐dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well‐defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Despite significant recent progress in the area of translational genomics of neuroblastoma, the overall survival rates for children with high-risk NB continue to be not more than 5 years due to tumor relapse and/or drug-resistant tumors. Herein we report on the development of a neuroblastoma targeting nanometric (130-150 nm) circulation stable liposomal system prepared from a novel nipecotic acid-derived cationic amphiphile (NACA). The size ranges of liposomes (130-150 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The findings in the gel electrophoresis assay revealed that siRNAs encapsulated within the liposomes of NACA (with 90% entrapment efficiency) are protected from attack by RNase. Cellular uptake experiments using FAM-siRNA loaded liposomes of NACA showed the liposomal entry in human neuroblastoma cells (IMR-32) to be mediated via the GABA receptor. CDC20siRNA-loaded liposomes of NACA caused significantly higher CDC20 gene silencing efficiency in IMR-32 cells compared to CDC20 gene knockdown efficiency mediated by CDC20siRNA-loaded control non-targeting liposomes (NTL). The findings in the annexin-V binding based flow cytometric apoptosis assay and MTT-based cellular cytotoxicity assay support the notion that pronounced (80%) neuroblastoma cell death upon treatment with CDC20siRNA & PTX co-loaded liposomes of NACA presumably originates from enhanced apoptosis of cells. Importantly, intravenously administered CDC20siRNA & PTX co-loaded liposomes of NACA significantly inhibited growth of xenografted human neuroblastoma in athymic nude mice. The presently disclosed strategy of co-delivering potent anticancer siRNA and small molecule chemotherapeutics using liposomes of NACA opens a new door for combating the dreaded disease of neuroblastoma.