Sukanya Bhunia

Covalent organic frameworks (COFs) are an emerging class of porous organic polymers with a broad spectrum of possible applications because of their large void spaces and modular pores. Despite excellent cytocompatibility, porosity, and biodegradability of COFs, their practical implementations in nanomedicine have been limited due to low water dispersibility and poor processability into nanodimensions. There are limited reports on nanoscale covalent organic frameworks, which can exhibit excellent drug loading capacity and pH‐responsive drug release. Herein, a water‐dispersible 2D COF‐based nanocarrier is reported for pH‐responsive targeted delivery of therapeutics (doxorubicin) to cancer cells. Particularly, a hydrolytically susceptible boronate ester‐based covalent organic framework (COF‐5) is supramolecularly stabilized with an amphiphilic polymer, Pluronic F127 (PLU), to obtain COF‐PLU nanoparticles with a size of ~185 nm and a thickness of ~25 nm. A high doxorubicin loading in the COF‐based nanocarrier (>90% drug loading efficiency and ~35% drug loading capacity) and pH‐responsive drug release are observed. Furthermore, the surface modification of Dox‐loaded polymer‐stabilized COF‐5 with hyaluronic acid demonstrates selective delivery of doxorubicin to cancer cells. Our study demonstrates a facile strategy for developing a pH‐responsive COF‐based nanocarrier with excellent drug‐loading capacity for targeted delivery of therapeutics to cancer cells.

Ovarian cancer is a global silent killer in women and is the second most common cause of gynecologic cancer-related deaths. Despite significant research and advances in treatment, ovarian cancer treatment remains a challenge, as it is diagnosed in an advanced stage and has a very high rate of recurrence following initial therapy. There is a compelling need to develop effective therapeutics for the treatment of ovarian cancer. This review highlights the recent advancements in nanoparticle-based drug-delivery systems and their expanding scope of treatments and diagnostics in ovarian cancer. In this article, we provide an overview of the innate immune response elicited by external delivery carriers. The review details the ongoing progress in nanotechnology for ovarian cancer treatment, including advances in nanoimmunotherapy and the potential of nanoparticle-based formulations for combating ovarian cancer. Recent diagnostic and prognostic tools used for ovarian cancer have been elaborated. The review also underscores the role of artificial intelligence in advancing current clinical diagnosis protocols. Challenges and future perspectives of nanocarriers for ovarian cancer treatment are also discussed in detail. This review uniquely integrates the role of innate immune responses with advances in nanotechnology for ovarian cancer, providing a comprehensive and interdisciplinary perspective that has not been previously addressed.

Brain cancers and neurodegenerative diseases are on the rise, treatments for central nervous system (CNS) diseases remain limited. Despite the significant advancement in drug development technology with emerging biopharmaceuticals like gene therapy or recombinant protein, the clinical translational rate of such biopharmaceuticals to treat CNS disease is extremely poor. The blood–brain barrier (BBB), which separates the brain from blood and protects the CNS microenvironment to maintain essential neuronal functions, poses the greatest challenge for CNS drug delivery. Many strategies have been developed over the years which include local disruption of BBB via physical and chemical methods, and drug transport across BBB via transcytosis by targeting some endogenous proteins expressed on brain-capillary. Drug delivery to brain is an ever-evolving topic, although there were multiple review articles in literature, an update is warranted due to continued growth and new innovations of research on this topic. Thus, this review is an attempt to highlight the recent strategies employed to overcome challenges of CNS drug delivery while emphasizing the necessity of investing more efforts in CNS drug delivery technologies parallel to drug development.

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.

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.

Blood-brain barrier (BBB), a unique membrane barrier formed by closely stitched brain capillary endothelial cells (BCEC) with tight cellular junctions, separates brain from the circulating blood to protect it from bloodborne pathogens. BBB greatly limits the entry of chemotherapeutics to brain, and in consequence, it is a major obstacle for treating brain tumor. Advances in designing efficient nano-drug carriers are opening new avenues for overcoming this uphill systemic challenge. This book chapter describes current understanding of nanocarriers-mediated noninvasive drug targeting to brain tumor. Design principles behind the construction of the most promising recently designed receptor and transporter selective nano-drug carriers for combating brain tumors have been highlighted.

2D covalent organic frameworks (COFs) are an emerging class of crystalline porous organic polymers with a wide‐range of potential applications. However, poor processability, aqueous instability, and low water dispersibility greatly limit their practical biomedical implementation. Herein, a new class of hydrolytically stable 2D COFs for sustained delivery of drugs to direct stem cell fate is reported. Specifically, a boronate‐based COF (COF‐5) is stabilized using amphiphilic polymer Pluronic F127 (PLU) to produce COF‐PLU nanoparticles with thickness of ≈25 nm and diameter ≈200 nm. These nanoparticles are internalized via clathrin‐mediated endocytosis and have high cytocompatibility (half‐inhibitory concentration ≈1 mg mL⁻¹). Interestingly, the 2D COFs induce osteogenic differentiation in human mesenchymal stem cells, which is unique. In addition, an osteogenic agent—dexamethasone—is able to be loaded within the porous structure of COFs for sustained delivery which further enhances the osteoinductive ability. These results demonstrate for the first time the fabrication of hydrolytically stable 2D COFs for sustained delivery of dexamethasone and demonstrate its osteoinductive characteristics.

Molybdenum disulfide (MoS₂) nanostructures are layered 2D transition metal dichalcogenide with unique physical, chemical, and biological properties. These properties can further be optimized during the synthesis process by introducing atomic defects within the layered nanostructure of MoS₂. Herein, MoS₂ nanostructure with varying defect density is synthesized and highly hydrophilic MoS₂ nanostructure is shown to be obtained by increasing the atomic defects. This hydrophilic MoS₂ nanostructure is further incorporated within electrospun polyacrylonitrile (PAN) nanofibers to improve the physical and chemical properties. Uniform distribution of MoS₂ nanoassemblies is observed within the PAN nanofibers. Significant increase in electrical conductivity, thermal stability, and mechanical strength of PAN nanofibers are obtained due to MoS₂ addition. Interestingly, the addition of MoS₂ nanostructure resulted in enhanced protein adsorption as well as cytocompatibility of these hybrid PAN‐MoS₂ nanofibers due to hydrophilic characteristics of MoS₂ nanoassemblies. It is expected that these hybrid PAN‐MoS₂ nanofibers can potentially be used for a variety of biomedical applications including drug delivery, tissue engineering, and biosensing.

Covalent organic frameworks (COFs) are an emerging class of organic crystalline polymers with well‐defined 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, 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 biomedical applications of 2D COFs specifically for drug delivery, phototherapy, biosensing, bioimaging, biocatalysis, and antibacterial activity are summarized. In addition, current challenges and emerging approaches in designing 2D COFs for advanced biomedical applications are discussed.