Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration.

Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.

Diosgenin loaded cellulose nanoonion impedes different stages of protein aggregation induced cell death via alleviating mitochondrial dysfunction and upregulation of autophagy.

Protein aggregation is a multifaceted phenomenon prevalent in the progression of neurodegenerative diseases, yielding aggregates of diverse sizes. Recently, increased attention has been directed towards early protein aggregates due to their pronounced toxicity, largely stemming from inflammation mediated by reactive oxygen species (ROS). This study advocates for a therapeutic approach focusing on inflammation control rather than mere ROS inhibition in the context of neurodegenerative disorders. Here, we introduced Camellia sinensis cellulose nanoonion (CS-CNO) as an innovative, biocompatible nanocarrier for encapsulating the phytosteroid diosgenin (DGN@CS-CNO). The resulting nano-assembly, manifesting as spherical entities with dimensions averaging ~180-220 nm, exhibits a remarkable capacity for the gradual and sustained release of approximately 39-44 % of DGN over a 60-hour time frame. DGN@CS-CNO displays a striking ability to inhibit or disassemble various phases of hen egg white lysozyme (HEWL) protein aggregates, including the early (HEWLEA) and late (HEWLLA) stages. In vitro experiments employing HEK293 cells underscore the potential of DGN@CS-CNO in mitigating cell death provoked by protein aggregation. This effect is achieved by ameliorating ROS-mediated inflammation and countering mitochondrial dysfunction, as evidenced by alterations in TNFα, TLR4, and MT-CO1 protein expression. Western blot analyses reveal that the gradual and sustained release of DGN from DGN@CS-CNO induces autophagy, a pivotal process in dismantling intracellular amyloid deposits. In summary, this study not only illuminates a path forward but also presents a compelling case for the utilization of phytosteroid as a formidable strategy against neuroinflammation incited by protein aggregation.

Erythrocyte Membrane Cloaked Cytokine Functionalized Gold Nanoparticles Create Localized Controlled Inflammation for Rapid In Vitro Wound Healing.

Due to impaired wound healing, millions of acute and chronic wound cases with increased morbidity have been recorded in the developed countries. The primary reason has been attributed to uncontrolled inflammation at the wound site, which makes healing impossible for years. The use of red blood cell (RBC) ghosts or erythrocyte membranes for different theranostic applications has gained significant attention in recent years due to their biocompatibility and biomimicking properties. Our study builds upon this concept by presenting a new approach for creating an improved and controlled inflammatory response by employing RBC ghost encapsulated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) modified AuNPs (gold nanoparticles) for accelerating the wound healing at early postinjury stage (∼48 h). The results suggested that the developed GTNFα-IL6@AuNPs created a controlled and time dependent TNF-α response and showed increased reactive oxygen species generation at ∼12 h. Further, proper M1/M2 functional transition of macrophages was observed in macrophages at different time intervals. The expression results suggested that the levels of wound healing biomarkers like transforming growth factor-ß (1.8-fold) and collagen (2.4-fold) increased while matrix metalloproteinase (3-8-fold) levels declined at later stages, which possibly increased the cell migration rate of NP treated cells to ∼90%. Hence, we are here reducing the timeline of the inflammatory phase of wound healing by actually creating a controlled inflammatory response at an early postinjury stage and further assisting in regaining the ability of cells for wound remodelation and repair. We intend that this new approach has the potential to improve the current treatment strategies for wound healing and skin repair under both in vitro and in vivo conditions.

A review on nanotechnological perspective of "the amyloid cascade hypothesis" for neurodegenerative diseases.

Neurodegenerative diseases (NDs) are characterized by progressive degeneration of neurons which deteriorates the brain functions. An early detection of the onset of NDs is utmost important, as it will provide the fast treatment strategies to prevent further progression of the disease. Conventionally, accurate diagnosis of the brain related disorders is difficult in their early phase. To solve this problem, nanotechnology based neurofunctional imaging and biomarker detection techniques have been developed which allows high specificity and sensitivity towards screening and diagnosis of NDs. Another challenge to treat the brain related disorders is to overcome the complex integrity of blood-brain-barrier (BBB) for the delivery of theranostic agents. Fortunately, utilization of nanomaterials has been pursued as promising strategy to address this challenge. Herein, we critically highlighted the recent improvements in the field of neurodiagnostic and therapeutic approaches involving innovative strategies for diagnosis, and inhibition of protein aggregates. We have provided particular emphasis on the use of nanotechnology which can push forward the blooming research growth in this field to win the battle against devastating NDs.

Carbon nanosphere based bifunctional oxidoreductase nano-catalytic agent to mitigate hypoxia in cancer cells.

Developing metal-free carbon nanozyme for tumor hypoxia is difficult. In biomedical applications, especially in the case of biomolecular detection, extensive research has been done on nanozymes with enzyme-mimicking catalytic activity. However, there are considerably fewer investigations on targeted nano-catalytic tumor therapy. Nano catalytic medicine-enabled chemotherapy is a safe and promising treatment strategy that involves the conversion of excess H2O2 into O2 in a tumor environment. Here we have synthesized carbon nanosphere (CNS) using the Camellia sinensis plant (CS-CNS). Further surface functionalization was achieved via nitrilotriacetic acid conjugation (NTA@CS-CNS). A stability study of synthesized nanozyme in the presence of various cations, anions, and 5 different pH range suggested the robustness of carbon based nanoassembly. The catalytic in vitro study shows that NTA@CS-CNS mimics peroxidase and catalase using TMB and H2O2 as substrates. NTA@CS-CNS showed Km and Vmax values of ~ 193.2 µM and 0.43 µM/s, ~ 413 µM and 1.42 µM/s, and ~ 378 µM and 1.63 µM/s, respectively when H2O2 and TMB was used for CAT and POD activity. Results showed that NTA@CS-CNS in combination with SFN and laser irradiation reduces hypoxia. Hence, our study could pave the path for the development of different non-toxic nano catalytic therapy for tumors in cancerous cells.

Protein-Cloaked Nanoparticles for Enhanced Cellular Association and Controlled Pathophysiology via Immunosurveillance Escape.

Weak interactions play an important role in soft corona (SC) formation and thus help in evaluating the biological fate of the nanoparticles (NPs). Preadsorption of specific proteins on the NP surface, leading to SC formation, has been found to help NPs in evading immunosurveillance. However, the role of different preadsorbed biomolecules in determining the NP pathophysiology and cellular association, upon their re-exposure to in vivo conditions, still remains elusive. Here, differently charged gold NPs were precoated with two different blood components, viz. red blood cells and human serum albumin protein, and these were then re-exposed to human serum. Cloaking NPs with protein improved the NP colloidal stability and other physico-chemical properties along with increased cellular association. Detailed proteomic analysis suggested that protein-camouflaged NPs showed a decrease in immune-responsive proteins compared to their bare counterparts. Further, it was also observed that the secondary protein signature on the NP surface was governed by primary protein coating; however, the event was more or less NP charge-independent. This study will pave the path for future strategies to make NPs invincible to the immunosurveillance system of the body.

The curious cases of nanoparticle induced amyloidosis during protein corona formation and anti-amyloidogenic nanomaterials: Paradox or prejudice?

Protein corona (PC) formation remains a major hurdle in the successful delivery of nanomedicines to the target sites. Interacting proteins have been reported to undergo structural changes on the nanoparticle (NP) surface which invariably impacts their biological activities. Such structural changes are the result of opening of more binding sites of proteins to adsorb on the NP surface. The process of conversion of α-helix proteins to their ß-sheet enriched counterpart is termed as amyloidosis and in case of PC formation, NPs apparently play the crucial role of being the nucleation centres where this process takes place. Conversely, increasing numbers of artificial nano-chaperones are being used to treat the protein misfolding disorders. Anti-amyloidogenic nanomaterials (NM) have been gaining utmost importance in inhibiting Aß42 (hallmark peptide for Alzheimer's disease) and Hen egg white lysozyme (HEWL, model protein for systemic amyloidosis) aggregation. Interestingly, in this process, NPs inhibit protein ß-sheet enrichment. These two seemingly opposite roles of NPs, propelling confirmatory change onto the smorgasbord of adsorbed native proteins and the ability of NPs in inhibiting amyloidosis creates a paradox, which has not been discussed earlier. Here, we highlight the key points from both the facets of the NP behaviour with respect to their physicochemical properties and the nature of proteins they adsorb onto them to unravel the mystery. BRIEF: Protein corona formation remains a major hurdle in achieving the desired efficacy of nanomedicine. Proteins when interact with nanoparticle (NP) surface, undergo both structural and biological changes. Again, NPs are known to exhibit anti-amyloidogenic behaviour where these play the crucial role of preventing any change in their native structure. Such seemingly different roles of NPs need sincere inquisition.