Anti-tuberculosis drugs used in a directly observed treatment short course (DOTS) schedule alter endocrine patterns and reduce the ovarian reserve and oocyte quality in the mouse.

CONTEXT: Tuberculosis is one of the major infectious diseases, with people of reproductive age group having a high risk of infection. AIMS: The present study was designed to understand the consequences of anti-tuberculosis drugs (ATDs) used in DOTS (directly observed treatment short course) schedule on ovarian function. METHODS: Adult female Swiss albino mice were orally administered with combinations of ATDs used in the DOTS schedule every day for 4weeks. At 2weeks after the cessation of ATDs administration, the endocrine changes and ovarian function were assessed in mice. KEY RESULTS: Administration of ATDs to mice resulted in a prolonged estrous cycle, reduced ovarian follicle reserve, alteration in FSH, LH, and progesterone level, and decreased the number of ovulated oocytes. Further, the degree of fragmentation, degeneration, abnormal distribution of cytoplasmic organelles, abnormal spindle organisation, and chromosomal misalignment were higher in oocytes that were ovulated following superovulation. Blastocysts derived from ATDs treated mice had significantly lower total cell numbers and greater DNA damage. A marginal increase in the number of resorbed fetuses was observed in all the ATDs treated groups except in the multidrug resistance treatment group. Male progeny of ATDs treated mice had decreased sperm count and lower progressive motility, while female progeny exhibited a non-significant reduction in the number of oocytes ovulated. CONCLUSIONS: Theresults of this study suggest that ATDs can have significant adverse effects on the ovarian reserve, cytoplasmic organisation of oocytes, and can potentially cause transgenerational changes. IMPLICATIONS: The findings of the present study indicate ovarian toxicity of ATDs and warrant further research in the direction of identifying alternate drugs with minimal toxicity, and strategies to mitigate the ovarian toxicity induced by these drugs.

Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy.

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.

Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea.

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1, are translationally regulated by SMED-PABPC2. Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration.

Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photothermal Chemotherapy.

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-AuI Cl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.

Palladium-Loaded Cucurbit[7]uril-Modified Iron Oxide Nanoparticles for C-C Cross-Coupling Reactions.

Cucurbit[7]uril modified iron oxide nanoparticles (CB[7]NPs) were loaded with palladium to form nano-catalysts (Pd@CB[7]NPs) that, with microwave heating, catalysed Suzuki-Miyaura, Sonogashira, and Mizoroki-Heck cross-coupling reactions. Reactions were run in environmentally benign 1:1 ethanol/water solvent under convenient aerobic conditions. In a preliminary screening, conversions and yields were uniformly high with turn over frequencies (TOF) ranging from 64 to 7360 h-1 . The nano-catalysts could be recovered with a magnet and reused several times (6 times for Suzuki-Miayura reaction) without loss of activity.

Supplementing zinc oxide nanoparticles to cryopreservation medium minimizes the freeze-thaw-induced damage to spermatozoa.

The sperm DNA integrity post cryopreservation of human semen samples is one of the serious concerns in human infertility treatment. In the present study, the beneficial effects of zinc oxide nanoparticles in preserving the functional ability of spermatozoa was explored. Ejaculates of normozoospermic men cryopreserved along with Zinc oxide nanoparticles (ZnONPs) exhibited non-significantly higher percentage of total and progressive motility in frozen-thawed samples compared to control. The sperm chromatin damage and malondialdehyde (MDA) level was significantly lower in ZnONPs group (P < 0.01 and P < 0.05 respectively) and the spermatozoa's ability to undergo acrosome reaction was also unaltered. Fluorescence microscopy and High resolution transmission electron microscopy analysis demonstrated that the ZnONPs do not penetrate the membrane of spermatozoa but stay around the spermatozoa. In conclusion, the presence of ZnONPs during cryopreservation appears to be beneficial to the spermatozoa as they withstand freeze-thaw process competently better than control, without any adverse effect shown.

Peptide-functionalized graphene oxide quantum dots as colorectal cancer theranostics.

Colorectal cancer (CRC) accounts for approximately 10% of all new cancer cases worldwide with significant morbidity and mortality. The current imaging techniques are lacking diagnostic precision while traditional chemotherapeutic strategies are limited by their adverse side effects and poor response in advanced stages. Targeted nanoparticles (NPs) can specifically bind to surface antigens on cancer cells and provide effective delivery of diagnostic and chemotherapeutic agent. Placenta-specific protein 1 (PLAC-1) is overexpressed in CRC and can be used as a target for detection and treatment of the disease. The aim of this work was to develop a targeted nanotheranostic agent for early diagnosis and inhibition of the malignant progression and metastasis of CRC. Graphene oxide quantum dots (QD) were covalently labeled with a peptide (GILGFVFTL) having high affinity to PLAC-1. The covalent coupling between the QD and the peptide was confirmed using a series of physicochemical and morphological characterization techniques. Confocal microscopy was used to evaluate the uptake of QD and QD-P in HCT-29, HT-116 and LS-180 CRC cell lines. Selective targeting of antigen PLAC-1 overexpressed on HT-29 and HCT-116 cells was measured by immunofluorescence. Cell proliferation, cell invasion and extent of PLAC-1 expression in CRC cells after treatment with QD and QD-P were determined. The prepared QD-P showed a significant increase in targeting and specific uptake in cells expressing the antigen PLAC-1 compared to non-functionalized QD. Treatment with QD-P also increased the cell cytotoxicity, reduced the invasiveness of HT-29 and HCT-116 cells by 38% and 62%, respectively, and downregulated the expression of PLAC-1 by 53% and 33%, respectively. These results highlight the potential use of QD-P as a theranostic agent for the detection and treatment of CRC cells expressing the antigen PLAC-1.

pH-Responsive Upconversion Mesoporous Silica Nanospheres for Combined Multimodal Diagnostic Imaging and Targeted Photodynamic and Photothermal Cancer Therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have gained considerable attention as potential alternatives to conventional cancer treatments. However, these approaches remain limited by low solubility, poor stability, and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome the aforementioned limitations, we engineered biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium, and gadolinium) and the PTA bismuth selenide (NaYF4:Yb/Er/Gd,Bi2Se3) enveloped in a mesoporous silica shell that encapsulates a PS, chlorin e6 (Ce6), within its pores. NaYF4:Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites Ce6 to generate cytotoxic reactive oxygen species (ROS), while Bi2Se3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging of the nanospheres. The mesoporous silica shell is coated with DPPC/cholesterol/DSPE-PEG to retain the encapsulated Ce6 and prevent serum protein adsorption and macrophage recognition that hinder tumor targeting. Finally, the coat is conjugated to the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into malignant cells in the mildly acidic microenvironment of tumors. The nanospheres facilitated tumor magnetic resonance and thermal and fluorescence imaging and exhibited potent NIR laser light-induced anticancer effects in vitro and in vivo via combined ROS production and localized hyperthermia, with negligible toxicity to healthy tissue, hence markedly extending survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.

pH-responsive upconversion mesoporous silica nanospheres for combined multimodal diagnostic imaging and targeted photodynamic and photothermal cancer therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have garnered considerable interest as non-invasive cancer treatment modalities. However, these approaches remain limited by low solubility, poor stability and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome these limitations, we have designed biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium and gadolinium) and bismuth selenide (NaYF 4 :Yb/Er/Gd,Bi 2 Se 3 ) within a mesoporous silica shell that encapsulates a PS, Chlorin e6 (Ce6), in its pores. NaYF 4 :Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites the Ce6 to generate cytotoxic reactive oxygen species (ROS), while the PTA Bi 2 Se 3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging (MRI) of the nanospheres. The mesoporous silica shell is coated with lipid/polyethylene glycol (DPPC/cholesterol/DSPE-PEG) to ensure retention of the encapsulated Ce6 and minimize interactions with serum proteins and macrophages that impede tumor targeting. Finally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into cancer cells within the mildly acidic tumor microenvironment. Following uptake by cancer cells in vitro , NIR laser irradiation of the nanospheres caused substantial cytotoxicity due to ROS production and hyperthermia. The nanospheres facilitated tumor MRI and thermal imaging, and exhibited potent NIR laser light-induced antitumor effects in vivo via combined PDT and PTT, with no observable toxicity to healthy tissue, thereby substantially prolonging survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.

Light-driven self-assembly of spiropyran-functionalized covalent organic framework.

Controlling the number of molecular switches and their relative positioning within porous materials is critical to their functionality and properties. The proximity of many molecular switches to one another can hinder or completely suppress their response. Herein, a synthetic strategy involving mixed linkers is used to control the distribution of spiropyran-functionalized linkers in a covalent organic framework (COF). The COF contains a spiropyran in each pore which exhibits excellent reversible photoswitching behavior to its merocyanine form in the solid state in response to UV/Vis light. The spiro-COF possesses an urchin-shaped morphology and exhibits a morphological transition to 2D nanosheets and vesicles in solution upon UV light irradiation. The merocyanine-equipped COFs are extremely stable and possess a more ordered structure with enhanced photoluminescence. This approach to modulating structural isomerization in the solid state is used to develop inkless printing media, while the photomediated polarity change is used for water harvesting applications.

Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice.

Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.

Ultra-low level optical detection of mercuric ions using biogenic gold nanotriangles.

Mercury is a serious environmental pollutant known to have detrimental health effects in all life forms. Here, we report the use of biologically synthesized aqueous gold nanotriangles for sensitive and selective optical detection of femto-molar levels of mercury ions by exploiting the high amalgamation tendency of mercury metal towards gold. Aqueous chloroaurate ions were reduced using lemongrass (Cymbopogon flexuosus) leaf extract at room temperature to form gold nanotriangles. Mercuric (Hg(2+)) ions were reduced in the presence of these triangles to facilitate amalgamation and the optical properties were monitored. We observe a significant change in the longitudinal plasmon absorption band of the nanotriangles even at femto-molar concentrations of mercuric ions. High-resolution transmission electron microscopy confirms changes in particle morphology at such low concentrations. This protocol shows no sensitivity to other environmentally relevant metal ions, including Pb(2+), Zn(2+), Cd(2+), Fe(2+), Ni(2+), Sr(2+), Ca(2+), Mn(2+), and Cu(2+), confirming further that change in the optical properties of gold nanotriangles in the presence of reduced mercuric ions is solely due to the strong amalgamation tendency of mercury metal.

Antimicrobial activity of zirconia (ZrO2) nanoparticles and zirconium complexes.

The antimicrobial activities of zirconia (ZrO2) nanoparticles and zirconium mixed ligand complexes were studied on bacterial strains of E. coli, S. aureus and fungal strain of A. niger. The nanoparticles of zirconia and Zr(IV) complexes with different amino acids as ligands were synthesized by hydrothermal method. X-ray diffraction (XRD) and HRTEM confirmed the crystalline nature and morphology of the synthesized products. The antimicrobial studies revealed that the zirconia exhibits activity only against the E. coli, whereas, the Zr(IV) complexes exhibits activity against both the bacteria: gram -ve E. coli and gram +ve S. aureus as well as fungal strains. The Zr(IV) complexes are found to possess significant antifungal activity against A. niger. The results are indicative of crystal plane-dependent antimicrobial activity of zirconia nanoparticles and complexes. The observed difference in the antibacterial activity of ZrO2 crystals and Zr(IV) complexes may be ascribed to the atomic arrangements of different exposed surfaces. On the basis of the study, it could be speculated that the ZrO2 nanoparticles with the same surface areas but with different shapes i.e., different active facets will show different antimicrobial activity.

Comparative study of leaching of silver nanoparticles from fabric and effective effluent treatment.

Nano silver (Ag(n)) is employed as an active antimicrobial agent, but the environmental impact of Ag(n) released from commercial products is unknown. The quantity of nanomaterial released from consumer products during use should be determined to assess the environmental risks of advancement of nanotechnology. This work investigated the amount of silver released from three different types of fabric into water during washing. Three different types of fabric were loaded with chemically synthesized Ag nanoparticles and washed repeatedly under simulated washing conditions. Variable leaching rates among fabric types suggest that the manufacturing process may control the release of silver reaching the waste water treatment plants. In an attempt to recover the Ag(n) for reutilization and to save it from polluting water, the effluents from the wash were efficiently treated with bacterial strains. This treatment was based on biosorption and was very efficient for the elimination of silver nanoparticles in the wash water. The process ensured the recovery of the Ag(n) leached into the effluent for reutilization, thus preventing environmental repercussions.

Synthesis of Self-Assembled Single Atomic Layer Gold Crystals-Goldene.

We report, for the first time, a technique to synthesize free-standing, one-atom thick 2D gold crystals (namely, goldene) and self-assembled 2D periodic arrays of goldene. High-resolution transmission electron microscopy (HRTEM) imaging of goldene revealed herringbone and honeycomb lattices, which are primarily gold surface features due to its reconstruction. Imaging of these surface-only features by a nonsurface characterization technique such as HRTEM is an unequivocal proof of the absence of three-dimensionality in goldene. Atomic force microscopy confirmed 1-2 Šthickness of goldene. High-resolution X-ray photoelectron spectroscopy (HR-XPS), selective area electron diffraction, and energy-dispersive X-ray spectroscopy confirmed the chemical identity of goldene. We discovered the phenomenon of electric field-induced self-assembly of goldene supracrystals with a herringbone structure and developed an electric field printing (e-print) technique for goldene arrays. Goldene showed a semiconductor response with a knee voltage of ∼3.2 V, and I/V spectroscopy revealed periodic room temperature Coulomb blockade oscillations. These observations are consistent with the theoretical calculations reported in the literature predicting enhanced Coulombic interactions between gold valence electrons and the nucleus in stable 2D gold. Goldene exhibited multiple, intense, and well-resolved optical absorption peaks and several fine bands across the UV-vis region, and we calculated its optical band gap to be 3.59 eV. Magnetic force microscopy measurements of goldene periodic arrays showed a ∼5 mV peak amplitude confirming its ferromagnetism. Optical and magnetic properties of goldene are consistent with those reported in the literature for 2D planar gold clusters with less than 12 atoms.

Fluorescence turn on amine detection in a cationic covalent organic framework.

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and have shown great potential for various applications. When functionalized with suitable emission sites, guest uptake via the ionic moieties of iCOFs can cause a significant change in luminescence, making them excellent candidates for chemosensors. In here, we present a luminescence sensor in the form of an ionic covalent organic framework (TGH+•PD) composed of guanidinium and phenanthroline moieties for the detection of ammonia and primary aliphatic amines. TGH+•PD exhibits strong emission enhancement in the presence of selective primary amines due to the suppression of intramolecular charge transfer (ICT) with an ultra-low detection limit of 1.2 × 10‒7 M for ammonia. The presence of ionic moieties makes TGH+•PD highly dispersible in water, while deprotonation of the guanidinium moiety by amines restricts its ICT process and signals their presence by enhanced fluorescence emission. The presence of ordered pore walls introduces size selectivity among analyte molecules, and the iCOF has been successfully used to monitor meat products that release biogenic amine vapors upon decomposition due to improper storage.

Magnetite/CdTe magnetic-fluorescent composite nanosystem for magnetic separation and bio-imaging.

A new synthesis protocol is described to obtain a CdTe decorated magnetite bifunctional nanosystem via dodecylamine (DDA) as cross linker. High resolution transmission electron microscopy (HRTEM), energy-dispersive x-ray spectroscopy (EDAX), vibrating sample magnetometry (VSM), Fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectroscopy (DRS) and fluorescence microscopy are used to characterize the constitution, size, composition and physical properties of these superparamagnetic-fluorescent nanoparticles. These CdTe decorated magnetite nanoparticles were then functionalized with anti-epidermal growth factor receptor (EGFR) antibody to specifically target cells expressing this receptor. The EGFR is a transmembrane glycoprotein and is expressed on tumor cells from different tissue origins including human leukemic cell line Molt-4 cells. The magnetite-CdTe composite nanosystem is shown to perform excellently for specific selection, magnetic separation and fluorescent detection of EGFR positive Molt-4 cells from a mixed population. Flow cytometry and confocal laser scanning microscopy results show that this composite nanosystem has great potential in antibody functionalized magnetic separation and imaging of cells using cell surface receptor antibody.

Fabrication of Al-matrix composites reinforced with amino functionalized boron nitride nanotubes.

Amino functionalized boron nitride nanotubes were used as the reinforcement material for the fabrication of Al-matrix composites using powder metallurgy process. It was found that the mechanical properties of these composites were improved significantly as compared to pure Al composites fabricated under similar conditions. The microhardness of these composites was found to improve by five times and compressive strength by 300% as compared to pure Al composites under similar processing conditions. The enhanced mechanical properties of these composites can be attributed to the proper dispersion of boron nitride nanotubes (BNNTs) in Al matrix and the formation of a strong interfacial bonding between BNNTs and Al matrix under the processing conditions. High-resolution transmission electron microscopy studies revealed the formation of transition layer of AlB2 which might lead to a better load transfer from Al matrix to the BNNTs. Further, these composites are believed to withstand high temperatures as compared to Al matrix composites reinforced with carbon nanotubes and, therefore, can be used for applications where lightweight and high strength materials are desired with stability at elevated temperatures.

Ultrasound-Triggered Liposomes Encapsulating Quantum Dots as Safe Fluorescent Markers for Colorectal Cancer.

Quantum dots (QDs) are a promising tool to detect and monitor tumors. However, their small size allows them to accumulate in large quantities inside the healthy cells (in addition to the tumor cells), which increases their toxicity. In this study, we synthesized stealth liposomes encapsulating hydrophilic graphene quantum dots and triggered their release with ultrasound with the goal of developing a safer and well-controlled modality to deliver fluorescent markers to tumors. Our results confirmed the successful encapsulation of the QDs inside the core of the liposomes and showed no effect on the size or stability of the prepared liposomes. Our results also showed that low-frequency ultrasound is an effective method to release QDs encapsulated inside the liposomes in a spatially and temporally controlled manner to ensure the effective delivery of QDs to tumors while reducing their systemic toxicity.

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function.

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimer's disease and type II diabetes, identified a tripyridylamide, ADH-6, that abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53's transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment effectively shrinks xenografts harboring mutant p53, while exhibiting no toxicity to healthy tissue, thereby substantially prolonging survival. This study demonstrates the successful application of a bona fide small-molecule amyloid inhibitor as a potent anticancer agent.