RESUMO
Surface-enhanced Raman scattering (SERS) has been extensively applied to detect complex analytes due to its ability to enhance the fingerprint signals of molecules around nanostructured metallic surfaces. Thus, it is essential to design SERS-active nanostructures with abundant electromagnetic hotspots in a probed volume according to the dimensions of the analytes, as the analytes must be located in their hotspots for maximum signal enhancement. Herein, we demonstrate a simple method for detecting robust SERS signals from multi-scaled bioanalytes, regardless of their dimensions in the liquid state, through a photothermally driven co-assembly with colloidal plasmonic nanoparticles as signal enhancers. Under resonant light illumination, plasmonic nanoparticles and analytes in the solution quickly assemble at the focused surface area by convective movements induced by the photothermal heating of the plasmonic nanoparticles without any surface modification. Such collective assemblies of plasmonic nanoparticles and analytes were optimized by varying the optical density and surface charge of the nanoparticles, the viscosity of the solvent, and the light illumination time to maximize the SERS signals. Using these light-induced co-assemblies, the intrinsic SERS signals of small biomolecules can be detected down to nanomolar concentrations based on their fingerprint spectra. Furthermore, large-sized biomarkers, such as viruses and exosomes, were successfully detected without labels, and the complexity of the collected spectra was statistically analyzed using t-distributed stochastic neighbor embedding combined with support vector machine (t-SNE + SVM). The proposed method is expected to provide a robust and convenient method to sensitively detect biologically and environmentally relevant analytes at multiple scales in liquid samples.
RESUMO
Solar energy is a plentiful renewable resource on Earth, with versatile applications in both domestic and industrial settings, particularly in solar steam generation (SSG). However, current SSG processes encounter challenges such as low efficiency and the requirement for extremely high concentrations of solar irradiation. Interfacial evaporation technology has emerged as a solution to these issues, offering improved solar performance compared to conventional SSG processes. Nonetheless, its implementation introduces additional complexities and costs to system construction. In this study, we present the development of hydrophilic, three-dimensional network-structured hydrogels with high porosity and swelling ratio using a facile fabrication technique. We systematically varied the mixing ratios of four key ingredients (polyethylene glycol diacrylate, PEGDA; polyethylene glycol methyl-ether acrylate, PEGMA; phosphate-buffered saline, PBS; and 2-hydroxy-2-methylpropiophenone, PI) to control the mean pore size and swelling ratio of the hydrogel. Additionally, plasmonic gold nanoparticles were incorporated into the hydrogel using a novel methodology to enhance solar light absorption and subsequent evaporation efficiency. The resulting material exhibited a remarkable solar efficiency of 77% and an evaporation rate of 1.6 kg m-2 h-1 under standard solar illumination (one sun), comparable to those of state-of-the-art SSG devices. This high efficiency can be attributed to the synergistic effects of the hydrogel's unique composition and nanoparticle concentration. These findings offer a promising avenue for the development of highly efficient solar-powered evaporation applications.
RESUMO
DNA-templated metallization has emerged as an efficient strategy for creating nanoscale-metal DNA hybrid structures with a desirable conformation and function. Despite the potential of DNA-metal hybrids, their use as combinatory therapeutic agents has rarely been examined. Herein, we present a simple approach for fabricating a multipurpose DNA superstructure that serves as an efficient photoimmunotherapy agent. Specifically, we adsorb and locally concentrate Au ions onto DNA superstructures through induced local reduction, resulting in the formation of Au nanoclusters. The mechanical and optical properties of these metallic nanoclusters can be rationally controlled by their conformations and metal ions. The resulting golden DNA superstructures (GDSs) exhibit significant photothermal effects that induce cancer cell apoptosis. When sequence-specific immunostimulatory effects of DNA are combined, GDSs provide a synergistic effect to eradicate cancer and inhibit metastasis, demonstrating potential as a combinatory therapeutic agent for tumor treatment. Altogether, the DNA superstructure-templated metal casting system offers promising materials for future biomedical applications.
Assuntos
Neoplasias , Fototerapia , Humanos , Fototerapia/métodos , DNA , Neoplasias/terapia , Imunoterapia , ÍonsRESUMO
Rapid, sensitive, inexpensive point-of-care molecular diagnostics are crucial for the efficient control of spreading viral diseases and biosecurity of global health. However, the gold standard, polymerase chain reaction (PCR) is time-consuming and expensive and needs specialized testing laboratories. Here, we report a low-cost yet fast, selective, and sensitive Plasmonic Optical Wells-Based Enhanced Rate PCR: POWER-PCR. We optimized the efficient optofluidic design of 3D plasmonic optical wells via the computational simulation of light-to-heat conversion and thermophoretic convection in a self-created plasmonic cavity. The POWER-PCR chamber with a self-passivation layer can concentrate incident light to accumulate molecules, generate rapid heat transfer and thermophoretic flow, and minimize the quenching effect on the naked Au surface. Notably, we achieved swift photothermal cycling of nucleic acid amplification in POWER-PCR on-a-chip in 4 min 24 s. The POWER-PCR will provide an excellent solution for affordable and sensitive molecular diagnostics for precision medicine and preventive global healthcare.
Assuntos
Temperatura Alta , Testes Imediatos , Simulação por Computador , Reação em Cadeia da PolimeraseRESUMO
Nanoplastics and microplastics (MPs) can significantly affect marine ecosystems and pose potential risks to human health. Although adverse effects stemming from direct exposure to MPs have been demonstrated at the cellular level in animal models, the potential toxicity of these materials in the human body remains uncertain. In this study, we investigated the three-dimensional (3D) behavior of dermal-derived cells exposed to MPs using artificially manufactured spherical primary polystyrene (PS) particles. To explore these effects, we used cellular spheroids as a 3D cell culture model, examined the size-dependent penetration of PS-MPs, and observed morphological alterations in the spheroids. Furthermore, we assessed changes in physiological activities, including reactive oxygen species, adenosine triphosphate, and lactate dehydrogenase, to elucidate the potential intra- and extracellular toxic reactions to PS-MPs. Additionally, our examination of cell-cell junctions and the extracellular matrix (ECM), along with analysis of the regulators involved in their decreased integrity, revealed negatively influenced changes in expression. This exposure study using spheroid models provides new insights into the potential toxicity of short-term exposure to MPs under conditions that closely resemble in vivo systems.
Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Humanos , Microplásticos/toxicidade , Plásticos/toxicidade , Ecossistema , Adesão Celular , Poliestirenos/toxicidade , Fibroblastos , Poluentes Químicos da Água/análiseRESUMO
Polymerase chain reaction (PCR) in small fluidic systems not only improves speed and sensitivity of deoxyribonucleic acid (DNA) amplification but also achieves high-throughput quantitative analyses. However, air bubble trapping and growth during PCR has been considered as a critical problem since it causes the failure of DNA amplification. Here we report bubble-free diatom PCR by exploiting a hierarchically porous silica structure of single-celled algae. We show that femtoliters of PCR solution can be spontaneously loaded into the diatom interior without air bubble trapping due to the surface hydrophilicity and pore structure of the diatom. We discover that a large pressure gradient between air bubbles and nanopores rapidly removes residual air bubbles through the periodically arrayed nanopores during thermal cycling. We demonstrate the DNA amplification by diatom PCR without air bubble trapping and growth. Finally, we successfully detect DNA fragments of SARS-CoV-2 with as low as 10 copies/µl by devising a microfluidic device integrated with diatoms assembly. We believe that our work can be applied to many PCR applications for innovative molecular diagnostics and provides new opportunities for naturally abundant diatoms to create innovative biomaterials in real-world applications.
Assuntos
Técnicas Biossensoriais , COVID-19 , Diatomáceas , Humanos , Diatomáceas/genética , Diatomáceas/química , SARS-CoV-2/genética , Reação em Cadeia da Polimerase , DNA/genética , Teste para COVID-19RESUMO
BACKGROUND: Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. RESULTS: In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. CONCLUSION: This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery.
Assuntos
Ouro , Nanopartículas Metálicas , Nanogéis , Alginatos , Sistemas de Liberação de MedicamentosRESUMO
While breathing, alveoli are exposed to external irritants, which contribute to the pathogenesis of lung disease. Therefore, in situ monitoring of alveolar responses to stimuli of toxicants under in vivo environments is important to understand lung disease. For this purpose, 3D cell cultures are recently employed for examining cellular responses of pulmonary systems exposed to irritants; however, most of them have used ex situ assays requiring cell lysis and fluorescent labeling. Here, an alveoli-like multifunctional scaffold is demonstrated for optical and electrochemical monitoring of cellular responses of pneumocytes. Porous foam with dimensions like the alveoli structure is used as a backbone for the scaffold, wherein electroactive metal-organic framework crystals, optically active gold nanoparticles, and biocompatible hyaluronic acid are integrated. The fabricated multifunctional scaffold allows for label-free detection and real-time monitoring of oxidative stress released in pneumocytes under toxic-conditions via redox-active amperometry and nanospectroscopy. Moreover, cellular behavior can be statistically classified based on fingerprint Raman signals collected from the cells on the scaffold. The developed scaffold is expected to serve as a promising platform to investigate cellular responses and disease pathogenesis, owing to its versatility in monitoring electrical and optical signals from cells in situ in the 3D microenvironments.
Assuntos
Pneumopatias , Nanopartículas Metálicas , Humanos , Células Epiteliais Alveolares , Ouro , IrritantesRESUMO
Obtaining single-molecular-level fingerprints of biomolecules and electron-transfer dynamic imaging in living cells are critically demanded in postgenomic life sciences and medicine. However, the possible solution called plasmonic resonance energy transfer (PRET) spectroscopy remains challenging due to the fixed scattering spectrum of a plasmonic nanoparticle and limited multiplexing. Here, multiplexed metasurfaces-driven PRET hyperspectral imaging, to probe biological light-matter interactions, is reported. Pixelated metasurfaces with engineered scattering spectra are first designed over the entire visible range by the precision nanoengineering of gap plasmon and grating effects of metasurface clusters. Pixelated metasurfaces are created and their full dark-field coloration is optically characterized with visible color palettes and high-resolution color printings of the art pieces. Furthermore, three different biomolecules (i.e., chlorophyll a, chlorophyll b, and cytochrome c) are applied on metasurfaces for color palettes to obtain selective molecular fingerprint imaging due to the unique biological light-matter interactions with application-specific biomedical metasurfaces. This metasurface-driven PRET hyperspectral imaging will open up a new path for multiplexed real-time molecular sensing and imaging methods.
Assuntos
Citocromos c , Imageamento Hiperespectral , Clorofila A , Transporte de Elétrons , Transferência de EnergiaRESUMO
The Fabry-Perot (FP) resonator is an intuitive and versatile optical structure owing to its uniqueness in light-matter interactions, yielding resonance with a wide range of wavelengths as it couples with photonic materials encapsulated in a dielectric cavity. Leveraging the FP resonator for molecular detection, a simple geometry of the metal-dielectric-metal structure is demonstrated to allow tuning of the enhancement factors (EFs) of surface-enhanced Raman scattering (SERS). The optimum near-field EF from randomly dispersed gold nano-gaps and dynamic modulation of the far-field SERS EF by varying the optical resonance of the FP etalon are systematically investigated by performing computational and experimental analyses. The proposed strategy of combining plasmonic nanostructures with FP etalons clearly reveals wavelength matching of FP resonance to excitation and scattering wavelengths plays a key role in determining the magnitude of the SERS EF. Finally, the optimum near-field generating optical structure with controlled dielectric cavity is suggested for a tunable SERS platform, and its dynamic SERS switching performance is confirmed by demonstrating information encryption through liquid immersion.
RESUMO
Conventional antibiotic-based treatment of bacterial infections remains one of the most difficult challenges in medicine because of the threat of multidrug resistance caused by indiscriminate abuse. To solve these problems, it is essential to develop an effective antibacterial agent that can be used at a small dose while minimizing the occurrence of multiple resistance. Metal-organic frameworks (MOFs), which are hyper-porous hybrid materials containing metal ions linked by organic ligands, have recently attracted attention because of their strong antibacterial activity through metal-ion release, unlike conventional antibiotics. In this study, we developed a photoactive MOF-derived cobalt-silver bimetallic nanocomposite (Ag@CoMOF) by simply depositing silver nanoparticles on a cobalt-based MOF through nanoscale galvanic replacement. The nanocomposite structure continuously releases antibacterial metal ions (i.e., Ag and Co ions) in the aqueous phase and exhibits a strong photothermal conversion effect of Ag nanoparticles, accompanied by a rapid temperature increase of 25-80 °C under near-infrared (NIR) irradiation. Using this MOF-based bimetallic nanocomposite, superior antibacterial activities were achieved by 22.1-fold for Escherichia coli and 18.3-fold for Bacillus subtilis enhanced inhibition of bacterial growth in a liquid culture environment compared with the generally used chemical antibiotics. In addition, we confirmed the synergistic enhancement of the antibacterial ability of the bimetallic nanocomposite induced by NIR-triggered photothermal heating and bacterial membrane disruption even when using a small amount of the nanocomposites. We envision that this novel antibacterial agent using MOF-based nanostructures will replace traditional antibiotics to circumvent multidrug resistance and present a new approach to antibiotic development.
Assuntos
Nanopartículas Metálicas , Nanocompostos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Cobalto/farmacologia , Nanocompostos/química , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coliRESUMO
The treatment for hepatocellular carcinoma (HCC), a severe cancer with a very high mortality rate, begins with the surgical resection of the primary tumor. For metastasis or for tumors that cannot be resected, sorafenib, a multi-tyrosine protein kinase inhibitor, is usually the drug of choice. However, typically, neither resection nor sorafenib provides a cure. The drug discovery strategy for HCC therapy is shifting from monotherapies to combination regimens that combine an immuno-oncology agent with an angiogenesis inhibitor. Herbal formulas can be included in the combinations used for this personalized medicine approach. In this study, we evaluated the HCC anticancer efficacy of the new herbal formula, HO-1089. Treatment with HO-1089 inhibited HCC tumor growth by inducing DNA damage-mediated apoptosis and by arresting HCC cell replication during the G2/M phase. HO-1089 also attenuated the migratory capacity of HCC cells via the inhibition of the expression of EMT-related proteins. Biological pathways involved in metabolism and the mitotic cell cycle were suppressed in HO-1089-treated HCC cells. HO-1089 attenuated expression of the G2/M phase regulatory protein, PLK1 (polo-like kinase 1), in HCC cells. HCC xenograft mouse models revealed that the daily oral administration of HO-1089 retarded tumor growth without systemic toxicity in vivo. The use of HO-1197, a novel herbal formula derived from HO-1089, resulted in statistically significant improved anticancer efficacy relative to HO-1089 in HCC. These results suggest that HO-1089 is a safe and potent integrated natural medicine for HCC therapy.
RESUMO
Emerging as substantial concerns in the ecosystem, submicron plastics have attracted much attention for their considerable hazards. However, their effect and even amount in the environment remain unclear. Establishing a substantive analytic platform is essential to expand the understanding of nanoplastics. However, the issues of diffusion and detection limit that arise from ultradiluted concentration and extremely small scales of nanoplastics leave significant technical hurdles to analyze the nanoplastic pollutants. In this study, we obtain effective Raman signals in real time from underwater nanoplastics with ultralow concentrations via AC electro-osmotic flows and dielectrophoretic tweezing. This enables the field-induced active collection of nanoplastics toward the optical sensing area from remote areas in a rapid manner, integrating conventional technical skills of preconcentration, separation, and identification in a single process. A step further, synergetic combination with plasmonic nanorods, accomplishes the highest on-site detection performance so far.
RESUMO
ARS-interacting multifunctional proteins 2 (AIMP2) is known to be a powerful tumour suppressor. However, the target AIMP2-DX2, AIMP2-lacking exon 2, is often detected in many cancer patients and cells. The predominant approach for targeting AIMP-DX2 has been attempted via small molecule mediated inhibition, but due to the lack of satisfactory activity against AIMP2-DX2, new therapeutic strategies are needed to develop a novel drug for AIMP2-DX2. Here, we report the use of the PROTAC strategy that combines small-molecule AIMP2-DX2 inhibitors with selective E3-ligase ligands with optimised linkers. Consequently, candidate compound 45 was found to be a degrader of AIMP2-DX2. Together, these findings demonstrate that our PROTAC technology targeting AIMP2-DX2 would be a potential new strategy for future lung cancer treatment.
Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , ProteóliseRESUMO
Plasmonic nanocavities have been used as a novel platform for studying strong light-matter coupling, opening access to quantum chemistry, material science, and enhanced sensing. However, the biomolecular study of cavity quantum electrodynamics (QED) is lacking. Here, we report the quantum electrodynamic behavior of chlorophyll-a in a plasmonic nanocavity. We construct an extreme plasmonic nanocavity using Au nanocages with various linker molecules and Au mirrors to obtain a strong coupling regime. Plasmon resonance energy transfer (PRET)-based hyperspectral imaging is applied to study the electrodynamic behaviors of chlorophyll-a in the nanocavity. Furthermore, we observe the energy level splitting of chlorophyll-a, similar to the cavity QED effects due to the light-matter interactions in the cavity. Our study will provide insight for further studies in quantum biological electron or energy transfer, electrodynamics, the electron transport chain of mitochondria, and energy harvesting, sensing, and conversion in both biological and biophysical systems.
Assuntos
Clorofila , Elétrons , Biofísica , Transferência de Energia , MitocôndriasRESUMO
11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Although 11ßHSD1 has been implicated in numerous metabolic syndromes, such as obesity and diabetes, the functional roles of 11ßHSD1 during progression of nonalcoholic steatohepatitis (NASH) and consequent fibrosis have not been fully elucidated. We found that pharmacological and genetic inhibition of 11ßHSD1 resulted in reprogramming of hepatic stellate cell (HSC) activation via inhibition of p-SMAD3, α-SMA, Snail, and Col1A1 in a fibrotic environment and in multicellular hepatic spheroids (MCHSs). We also determined that 11ßHSD1 contributes to the maintenance of NF-κB signaling through modulation of TNF, TLR7, ITGB3, and TWIST, as well as regulating PPARα signaling and extracellular matrix accumulation in activated HSCs during advanced fibrogenesis in MCHSs. Of great interest, the 11ßHSD1 inhibitor J2H-1702 significantly attenuated hepatic lipid accumulation and ameliorated liver fibrosis in diet- and toxicity-induced NASH mouse models. Together, our data indicate that J2H-1702 is a promising new clinical candidate for the treatment of NASH.
Assuntos
11-beta-Hidroxiesteroide Desidrogenases , Células Estreladas do Fígado , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células de Kupffer , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genéticaRESUMO
Hepatocellular carcinoma (HCC) is one of the most malignant human cancers, with a high mortality rate worldwide. Within an HCC tumor, cancer stem cells (CSCs) are responsible for tumor maintenance and progression and may contribute to resistance to standard HCC treatments. Previously, we characterized CD133+ cells as CSCs in primary HCC and identified chromenopyrimidinone (CPO) as a novel therapeutic for the effective treatment of CD133+ HCC. However, the biological function and molecular mechanism of CD133 remain unclear. Epigenetic alterations of CSCs have impacts on tumor initiation, progression, and therapeutic response. Here, we found that pharmacological and genetic depletion of CD133 in HCC attenuated the activity of DNA methyltransferases via control of DNMT3B stabilization. Genes were ranked by degree of promoter hypo/hyper methylation and significantly differential expression to create an "epigenetically activated by CPO" ranked genes list. Through this epigenetic analysis, we found that CPO treatment altered DNA methylation-mediated oncogenic signaling in HCCs. Specifically, CPO treatment inhibited Adenylyl cyclase-associated protein 1 (CAP1) expression, thereby reducing FAK/ERK activity and EMT-related proteins in HCC. Moreover, CPO improved the efficacy of sorafenib by inhibiting CAP1 expression and FAK/ERK activation in sorafenib-resistant HCC. These novel mechanistic insights may ultimately open up avenues for strategies targeting DNA methylation in liver cancer stem cells and provides novel therapeutic function of CPO for the effective treatment of sorafenib-resistant HCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Pirimidinonas/farmacologia , Adenilil Ciclases/metabolismo , Adenilil Ciclases/farmacologia , Adenilil Ciclases/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Oligopeptídeos , Sorafenibe/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêuticoRESUMO
New therapeutic concepts are critically needed for carbapenem-resistant Pseudomonas aeruginosa, an opportunistic pathogen particularly recalcitrant to antibiotics. The screening of around 230,000 small molecules yielded a very low hit rate of 0.002% after triaging for known antibiotics. The only novel hit that stood out was the antimetabolite oxythiamine. Oxythiamine is a known transketolase inhibitor in eukaryotic cells, but its antibacterial potency has not been reported. Metabolic and transcriptomic analyses indicated that oxythiamine is intracellularly converted to oxythiamine pyrophosphate and subsequently inhibits several vitamin-B1-dependent enzymes, sensitizing the bacteria to several antibiotic and non-antibiotic drugs such as tetracyclines, 5-fluorouracil, and auranofin. The positive interaction between 5-fluorouracil and oxythiamine was confirmed in a murine ocular infection model, indicating relevance during infection. Together, this study revealed a system-level significance of thiamine metabolism perturbation that sensitizes P. aeruginosa to multiple small molecules, a property that could inform on the development of a rational drug combination.
Assuntos
Oxitiamina , Tiamina Pirofosfato , Animais , Antibacterianos/farmacologia , Fluoruracila , Camundongos , Oxitiamina/metabolismo , Oxitiamina/farmacologia , Pseudomonas aeruginosa/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Tiamina/metabolismo , Tiamina/farmacologia , Tiamina Pirofosfato/análise , Tiamina Pirofosfato/metabolismoRESUMO
Aminoacyl-tRNA synthetase (ARS) interacting multifunctional protein2 (AIMP2) plays a vital role in protein synthesis. However, a splicing variant in which the second of the four exons of AIMP2 is deleted, inhibits the tumor suppression activity of AIMP2. Herein, we describe our discovery of series of potent AIMP2-DX2 inhibitors that are targeting lung cancer. Optimization of series using ligand-based drug design strategy led to discovery of compound 35, a potent AIMP2-DX2 inhibitor that is the most efficacious in H460 and A549 cells. This benzodioxane series may represent good starting points for further lead optimization of the identification potential drug candidates for the AIMP2-DX2 targeted treatment of lung cancer.