High amylopectin in waxy maize synergistically affects seed germination and seedling vigour over traditional maize genotypes.

Waxy maize grains rich in amylopectin have emerged as a popular food and industrial raw materials. Here, a set of waxy inbreds having recessive waxy1 (wx1) gene derived through marker-assisted selection (MAS), and their original versions were evaluated for germination, seed vigour index-I and vigour index-II, electrical conductivity (EC) and enzymatic activities viz., dehydrogenase (DH), esterase (EST), peroxidase (POX), superoxide dismutase (SOD) and α-amylase (AMY). Waxy inbreds under study possessed average 97.8% amylopectin compared to 72.4% in original inbreds. Waxy versions showed 15.2% more test weight, 4.3% increase in germination, 22.7% higher seed vigour index-I and 28.3% higher seed vigour index-II, respectively, over the original inbreds. Further, activity of DH, EST, POX, SOD and AMY of MAS-derived waxy inbreds was more than that of original inbreds, whereas EC was less in improved inbreds compared to originals. Amylopectin exhibited strong positive correlations (r = 0.69 to 0.97**) with seed germination, vigour index-I and -II, DH, SOD, POX, EST and AMY activity. However, amylopectin showed negative correlation of - 0.82** with EC. Seed germination and seed vigour indices were also positively correlated with all enzymatic activities (r = 0.58 to 0.92**). The analysis revealed that waxy inbreds possess better seed vigour and enzymatic activities over traditional inbreds. This is the first report of synergistic effects of wx1 gene on seed germination, vigour and enzymatic activities in maize endosperm.

Biomaterials for Targeting Endoplasmic Reticulum in Cancer.

Endoplasmic reticulum (ER) is one of the most important sub-cellular organelles which controls myriads of biological functions including protein biosynthesis with proper functional folded form, protein misfolding, protein transport into Golgi body for secretion, Ca2+ homeostasis and so on. Subsequently, dysregulation in ER function leads to ER stress followed by disease pathology like cancer. Hence, targeting ER in the cancer cells emerged as one of the futuristic strategies for cancer treatment. However, the major challenge is to selectively and specifically target ER in the sub-cellular milieu in the cancer tissues, due to the lack of ER targeting chemical moieties to recognize the ER markers. To address this, in the last decade, numerous biomaterials were explored to selectively impair and image ER in cancer cells to induce ER stress. This review outlines those biomaterials which consists of carbon and silicon materials, lipid nanoparticles (liposomes and micelles), supramolecular self-assembled nanostructures, cell membrane-coated nanoparticles and metallic nanoparticles. Moreover, we also discuss the challenges and possible solutions of this promising field to usher the readers towards next-generation ER targeted cancer therapy.

Mutant crtRB1 gene negates the unfavourable effects of opaque2 gene on germination and seed vigour among shrunken2-based biofortified sweet corn genotypes.

Sweet corn is one of the most popular vegetables worldwide. However, traditional shrunken2 (sh2 )-based sweet corn varieties are poor in nutritional quality. Here, we analysed the effect of (1) ß-carotene hydroxylase1 (crtRB1 ), (2) opaque2 (o2 ) and (3) o2+crtRB1 genes on nutritional quality, germination, seed vigour and physico-biochemical traits in a set of 27 biofortified sh2 -based sweet corn inbreds. The biofortified sweet corn inbreds recorded significantly higher concentrations of proA (16.47µg g-1 ), lysine (0.36%) and tryptophan (0.09%) over original inbreds (proA: 3.14µg g-1 , lysine: 0.18%, tryptophan: 0.04%). The crtRB1 -based inbreds had the lowest electrical conductivity (EC), whereas o2 -based inbreds possessed the highest EC. The o2 +crtRB1 -based inbreds showed similar EC to the original inbreds. Interestingly, o2 -based inbreds also had the lowest germination and seed vigour compared to original inbreds, whereas crtRB1 and o2 +crtRB1 introgressed sweet corn inbreds showed similar germination and seed vigour traits to their original versions. This suggested that the negative effect of o2 on germination, seed vigour and EC is nullified by crtRB1 in the double mutant sweet corn. Overall, o2 +crtRB1 -based sweet corn inbreds were found the most desirable over crtRB1 - and o2 -based inbreds alone.

Chimeric Small Molecules for Detouring Drugs into Mitochondria to Engender Apoptosis in Cancer Cells.

Mitochondrion has appeared as one of the important targets for anti-cancer therapy. Subsequently, small molecule anti-cancer drugs are directed to the mitochondria for improved therapeutic efficacy. However, simultaneous imaging and impairing mitochondria by a single probe remained a major challenge. To address this, herein Chimeric Small Molecules (CSMs) encompassing drugs, fluorophore and mitochondria homing moiety were designed and synthesized through a concise strategy. Screening of the CSMs in a panel of cancer cell lines (HeLa, MCF7, A549, and HCT-116) revealed that one of the CSMs comprising Indomethacin V exhibited remarkable cervical cancer cell (HeLa) killing (IC50 =0.97 µM). This lead CSM homed into the mitochondria of HeLa cells within 1 h followed by mitochondrial damage and reactive oxygen species (ROS) generation. This novel Indomethacin V-based CSM-mediated mitochondrial damage induced programmed cell death (apoptosis). We anticipate these CSMs can be used as tools to understand the drug effects in organelle chemical biology in diseased states.

Small-Molecule Endoplasmic Reticulum Stress Inducer Triggers Apoptosis in Cancer Cells.

Endoplasmic reticulum (ER) is highly critical for the sub-cellular protein synthesis, post-translational modifications and myriads of signalling pathways to maintain cellular homeostasis. Consequently, dysregulation in the ER functions leads to the ER stress in different pathological situations including cancer. Hence, exploring small molecules to induce ER stress emerged as one of the unorthodox strategies for future cancer therapeutics. However, development of ER targeted novel small molecules remains elusive due to the dearth of ER targeting moieties. Herein we have synthesized a small library of 3-methoxy-pyrrole-enamine through a concise strategy. Screening of this library in cervical (HeLa), colon (HCT-116), breast (MCF7) and lung cancer (A549) cells identified a novel small molecule which localized into the ER of the HeLa cervical cancer cells within 3 h, induced ER stress through the increased expression of ER stress markers (CHOP, IRE1α, PERK, BiP and Cas-12) and triggered the programmed cell death (apoptosis) leading to remarkable HeLa cell killing. This novel small molecule can be explored further as a tool to understand the chemical biology of ER towards the development of ER targeted cancer therapeutics.

Dog-bone shaped gold nanoparticle-mediated chemo-photothermal therapy impairs the powerhouse to trigger apoptosis in cancer cells.

The mitochondrion has emerged as one of the uncommon targets in cancer therapeutics due to its involvement in cancer generation and progression. Consequently, nanoplatform mediated delivery of anti-cancer drugs into the mitochondria of cancer tissues demonstrated immense potential in cancer treatment. In the last couple of decades, gold nanoparticles have gained incredible attention in biomedical applications due to their easy synthesis, size-shape tenability, optical properties and outstanding photothermal ability. However, application of gold nanoparticles to target mitochondria to induce the chemo-photothermal effect in cancer has remained in its infancy. To address this, herein we have engineered dog-bone shaped gold nanoparticles (Mito-AuDB-NPs) comprising cisplatin and 10-hydroxycamptothecin as chemotherapeutic drugs along with the triphenylphosphonium (TPP) cation for mitochondria homing. Mito-AuDB-NPs exhibited a remarkable increase in temperature till 56 °C upon 18 min irradiation with 740 nm NIR LED light with a power density of 0.9 W cm-2. These Mito-AuDB-NPs successfully homed into the mitochondria of HeLa cervical cancer cells within 1 h and induced mitochondrial outer membrane permeabilization (MOMP) under the chemo-photothermal effect leading to the generation of reactive oxygen species (ROS). This Mito-AuDB-NP-mediated mitochondrial damage triggered programmed cell death (apoptosis) by decreasing the expression of anti-apoptotic Bcl-2/Bcl-xl and increasing the expression of pro-apoptotic BAX followed by caspase-3 cleavage towards extraordinary HeLa cell killing in a synergistic manner without showing toxicity towards non-cancerous RPE-1 human epithelial retinal pigment cells. We anticipate that this dog-bone shaped gold nanoparticle-mediated chemo-photothermal impairment of mitochondria in the cancer cells can open a new direction towards organelle targeted cancer therapy.

Small Molecule AIEgens for Illuminating Sub-Cellular Endoplasmic Reticulum, Mitochondria, and Lysosomes.

Organelles are the working hubs of the cells. Hence, visualizing these organelles inside the cells is highly important for understanding their roles in pathological states and development of therapeutic strategies. Herein, we report the development of a novel highly substituted oxazoles with modular scaffolds (AIE-ER, AIE-Mito, and AIE-Lyso), which can home into endoplasmic reticulum (ER), mitochondria, and lysosomes inside the cells. These oxazoles showed remarkable aggregation-induced emission (AIE) property in water and in the solid state due to dual intramolecular H-bonding, which was confirmed by pH- and temperature-dependent fluorescence studies followed by molecular dynamics (MD) simulations and density functional theory (DFT) calculations. Confocal laser scanning microscopy studies revealed that AIE-ER, AIE-Mito, and AIE-Lyso efficiently homed into ER, mitochondria and lysosomes, respectively, in the HeLa cervical cancer cells and non-cancerous human retinal pigment epithelial RPE-1 cells within 3 h without showing any toxicity to the cells with high sub-cellular photostability. To the best of our knowledge, this is the first report of highly substituted oxazole-based small molecule AIEgens for organelle imaging. We anticipate these novel AIEgens have promise to image sub-cellular organelles in different diseased states as well as understanding the inter-organelle interactions towards the development of novel therapeutics.

Mitochondria Targeted AIE Probes for Cancer Phototherapy.

In recent years, mitochondrion (powerhouse of the cells) gained lots of interest as one of the unorthodox targets for futuristic cancer therapy. As a result, novel small molecules were developed to damage and image mitochondria in cancer models. In this context, aggregation-induced emission probes (AIEgens) received immense attention due to their applications in mitochondria-targeted biosensing, imaging, and biomedical theranostics. On the other hand, phototherapy (photodynamic and photothermal) has emerged as a powerful alternative to manage cancer due to its less invasive nature. However, merging these two areas to engineer mitochondria-targeted phototherapeutic probes for cancer diagnosis and treatment has remained a major challenge. In this mini-review, we will outline the development of novel mitochondria-targeted small molecule AIEgens as imaging agents and photosensitizers for photodynamic therapy along with dual photodymanic-phototheramal therapy and chemo-photodynamic therapy. We will also highlight the current challenges in developing mitochondria-targeted photothermal therapy probes for future biomedical theranostic applications to manage cancer.

Illuminating Sub-Cellular Organelles by Small Molecule AIEgens.

Sub-cellular organelles play a critical role in a myriad biological phenomena. Consequently, organelle structures and functions are invariably highjacked in diverse diseases including metabolic disorders, aging, and cancer. Hence, illuminating organelle dynamics is crucial in understanding the diseased states as well as developing organelle-targeted next generation therapeutics. In this review, we outline the novel small molecules which show remarkable aggregation-induced emission (AIE) properties due to restriction in intramolecular motion (RIM). We outline the examples of small molecules developed to image organelles like mitochondria, endoplasmic reticulum (ER), Golgi, lysosomes, nucleus, cell membrane and lipid droplets. These AIEgens have tremendous potential for next-generation phototherapy.

Chimeric nanoparticles for targeting mitochondria in cancer cells.

Mitochondrial dysfunction is implicated in myriad diseases, including cancer. Subsequently, targeting mitochondrial DNA (mt-DNA) in cancer cells has emerged as an unorthodox strategy for anti-cancer therapy. However, approaches targeting only one component of the mitochondrial "central dogma" can be evaded by cancer cells through various mechanisms. To address this, herein, we have engineered mitochondria-targeting cholesterol-based chimeric nanoparticles (mt-CNPs) consisting of cisplatin, camptothecin, and tigecycline, which can simultaneously impair mt-DNA, mitochondrial topoisomerase I (mt-Top1), and mitochondrial ribosomes. mt-CNPs were characterized as being positively charged, spherical in shape, and 187 nm in diameter. Confocal microscopy confirmed that mt-CNPs efficiently localized into the mitochondria of A549 lung cancer cells within 6 h, followed by mitochondrial morphology damage and the subsequent generation of reactive oxygen species (ROS). mt-CNPs showed remarkable cancer-cell killing abilities compared to free-drug combinations in A549 (lung), HeLa (cervical), and MCF7 (breast) cancer cells. These mitochondria-targeting lipidic chimeric nanoparticles could be explored further to impair multiple targets in mitochondria, helping researchers to gain an understanding of mitochondrial translational and transcriptional machinery and to develop new strategies for cancer therapy.

Characterization of crtRB1- and vte4-based biofortified sweet corn inbreds for seed vigour and physico-biochemical traits.

Sweet corn possessing recessive shrunken2 (sh2) gene is popular worldwide. Traditional sweet corn is poor in vitamin A and vitamin E. Plant breeders during the selection of sweet corn genotypes mainly emphasize on plant architecture and yield. Seed germination and seedling vigour play important role for early establishment in field, thereby increasing yield and income. Here, we analysed a set of 15 sh2-based biofortified sweet corn inbreds with crtRB1 (ß-carotene hydroxylase1) and vte4 (γ-tocopherol methyltransferase) genes and three traditional sh2-based sweet corn inbreds for nutritional quality, seed vigour and various physico-biochemical traits. The newly developed inbreds possessed significantly higher provitamin A (proA: 15.60 µg/g) and vitamin E [α-tocopherol (α-T): 20.42 µg/g] than the traditional sweet corn inbreds (proA: 2.51 µg/g, α-T: 11.16 µg/g). The biofortified sweet corn inbreds showed wide variation for germination (80.67-87.33%), vigour index-I (2097.17-2925.28 cm), vigour index-II (134.27-216.19 mg) and electrical conductivity (10.19-13.21 µS cm-1 g-1). Wide variation was also observed for dehydrogenase (1.29-1.59 OD g-1 ml-1), super oxide dismutase (4.01-9.82 g-1), peroxidase (11.66-16.47 µM min-1 g-1), esterase (22.98-34.76 nM min-1 g-1) and α-amylase (5.91-8.15 OD g-1 ml-1). Enrichment of proA and vitamin E in sweet corn did not affect seed vigour and physico-biochemical traits. Correlation analysis revealed that electrical conductivity and α-amylase activity was the reliable indicator for assessing seed germination and vigour. The study identified superior biofortified sweet corn genotypes that would contribute to better vigour and establishment in field. This is the first report of analysis of biofortified sweet corn genotypes for seed vigour and physico-biochemical traits.

Small molecule NSAID derivatives for impairing powerhouse in cancer cells.

Mitochondrion emerged as an important therapeutic target for anti-cancer strategy due to its involvement in cancer progression and development. However, progress of novel small molecules for selective targeting of mitochondria in cancer cells remained a major challenge. To address this, herein, through a concise synthetic strategy, we have synthesized a small molecule library of indomethacin and ibuprofen (non-steroidal anti-inflammatory drugs, NSAIDs) derivatives having triarylphosphonium moiety for mitochondria localization. Two of the library members were identified to induce mitochondrial damage through outer membrane permeabilization (MOMP) followed by generation of reactive oxygen species (ROS) leading to the remarkable MCF7 breast cancer cell death through apoptosis. These novel mitochondria targeted NSAID derivatives could open a new direction in understanding mitochondrial biology towards anti-cancer therapeutics in future.

γ-Resorcyclic Acid-Based AIEgens for Illuminating Endoplasmic Reticulum.

Endoplasmic reticulum (ER) has emerged as one of the interesting sub-cellular organelles due to its role in myriads of biological phenomena. Subsequently, visualization of the structure-function and dynamics of ER remained a major challenge to understand its involvement in different diseased states including cancer. To illuminate the ER, herein we have designed and synthesized γ-resorcyclic acid-based small molecules, which showed remarkable aggregation-induced emission (AIE) property in water. This AIE property was originated from the dual intramolecular H-bonding leading to the self-assembled 2D aggregation confirmed by pH- and temperature-dependent fluorescence quenching studies as well as scanning electron microscopy. These small molecules illuminated the sub-cellular ER in HeLa cervical cancer cells as well as non-cancerous RPE-1 human retinal epithelial cells within 1 h. These novel small molecules have the potential to light up ER chemical biology in diseased states.

Sugar metabolism during pre- and post-fertilization events in plants under high temperature stress.

High temperature challenges global crop production by limiting the growth and development of the reproductive structures and seed. It impairs the developmental stages of male and female gametogenesis, pollination, fertilization, endosperm formation and embryo development. Among these, the male reproductive processes are highly prone to abnormalities under high temperature at various stages of development. The disruption of source-sink balance is the main constraint for satisfactory growth of the reproductive structures which is disturbed at the level of sucrose import and utilization within the tissue. Seed development after fertilization is affected by modulation in the activity of enzymes involved in starch metabolism. In addition, the alteration in the seed-filling rate and its duration affects the seed weight and quality. The present review critically discusses the role of sugar metabolism in influencing the various stages of gamete and seed development under high temperature stress. It also highlights the interaction of the sugars with hormones that mediate the transport of sugars to sink tissues. The role of transcription factors for the regulation of sugar availability under high temperature has also been discussed. Further, the omics-based systematic investigation has been suggested to understand the synergistic or antagonistic interactions between sugars, hormones and reactive oxygen species at various points of sucrose flow from source to sink under high temperature stress.

Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells.

The endoplasmic reticulum (ER) is one of the crucial sub-cellular organelles controlling myriads of functions including protein biosynthesis, folding, misfolding and unfolding. As a result, dysregulation of these pathways in the ER is implicated in cancer development and progression. Subsequently, targeting the ER in cancer cells emerged as an interesting unorthodox strategy in next-generation anticancer therapy. However, development of small molecules to selectively target the ER for cancer therapy remained elusive and unexplored. To address this, herein, we have developed a novel small molecule library of sulfonylhydrazide-hydrazones through a short and concise chemical synthetic strategy. We identified a fluorescent small molecule that localized into the endoplasmic reticulum (ER) of HeLa cells, induced ER stress followed by triggering autophagy which was subsequently inhibited by chloroquine (autophagy inhibitor) to initiate apoptosis. This small molecule showed remarkable cancer cell killing efficacy in different cancer cells as mono and combination therapy with chloroquine, thus opening a new direction to illuminate ER-biology towards the development of novel anticancer therapeutics.

Nanoparticle-Mediated Routing of Antibiotics into Mitochondria in Cancer Cells.

In recent years, antibiotics have emerged as alternative medicines in cancer therapy due to their capability of mitochondrial dysfunction in cancer cells. However, antibiotics render collateral damage in noncancerous cells by targeting mitochondrial transcription and translational machinery. To address this, herein, we have engineered three different mitochondria-targeted cationic antibiotic (tigecycline)-loaded nanoparticles from cholesterol conjugates. Dynamic light scattering and electron microscopy confirmed the spherical morphology and a less than 200 nm hydrodynamic diameter for these nanoparticles. The triphenylphosphine-coated tigecycline-loaded nanoparticle (Mito-TPP-Tig-NP) was shown to be homed into the mitochondria of A549 lung cancer cells compared to the other cationic nanoparticles. These Mito-TPP-Tig-NPs indeed triggered mitochondrial morphology damage and generation of reactive oxygen species (ROS). All the mitochondria-targeted tigecycline-loaded nanoparticles showed improved cancer cell killing ability in A549 and HeLa cervical cancer cells compared to free tigecycline. Moreover, Mito-TPP-Tig-NPs showed much less toxicity toward noncancerous human embryonic kidney cells (HEK293) compared to free tigecycline. These antibiotic-loaded mitochondria-targeted nanoparticles can open up an avenue toward anticancer therapy.

Spatial targeting of Bcl-2 on endoplasmic reticulum and mitochondria in cancer cells by lipid nanoparticles.

The presence of the same proteins at different sub-cellular locations with completely different functions adds to the complexity of signalling pathways in cancer. Subsequently, it becomes indispensable to understand the diverse critical roles of these proteins based on their spatial distribution for the development of improved cancer therapeutics. To address this, in this work, we report the development of endoplasmic reticulum (ER) and mitochondria targeted nanoscale particles to spatially impair anti-apoptotic Bcl-2 protein in these organelles in HeLa cervical cancer cells. Confocal microscopy and gel electrophoresis confirmed that these nanoparticles selectively home into ER and mitochondria and inhibited Bcl-2 localized there. Interestingly, Bcl-2 inhibition in ER induced ER stress leading to autophagy, whereas inhibition of Bcl-2 in mitochondria leads to mitochondrial damage and programmed cell death (apoptosis) in HeLa cells. These nanoscale platforms can be further explored as chemical biology tools to decipher the location-function relationship of proteins towards next generation cancer therapeutics.

Mitochondrial Impairment by Cyanine-Based Small Molecules Induces Apoptosis in Cancer Cells.

Mitochondrion, the powerhouse of the cells, has emerged as one of the unorthodox targets in anticancer therapy due to its involvement in several cellular functions. However, the development of small molecules for selective mitochondrial damage in cancer cells remained limited and less explored. To address this, in our work, we have synthesized a natural product inspired cyanine-based 3-methoxy pyrrole small molecule library by a concise strategy. This strategy involves Vilsmeier and Pd(0) catalyzed Suzuki cross-coupling reactions as key steps. The screening of the library members in HeLa cervical cancer cells revealed two new molecules that localized into subcellular mitochondria and damaged them. These small molecules perturbed antiapoptotic (Bcl-2/Bcl-xl) and pro-apoptotic (Bax) proteins to produce reactive oxygen species (ROS). Molecular docking studies showed that both molecules bind more tightly with the BH3 domain of Bcl-2 proteins compared to obatoclax (a pan-Bcl-2 inhibitor). These novel small molecules arrested the cell cycle in the G0/G1 phase, cleaved caspase-3/9, and finally prompted late apoptosis. This small molecule-mediated mitochondrial damage induced remarkably high cervical cancer cell death. These unique small molecules can be further explored as chemical biology tools and next-generation organelle-targeted anticancer therapy.

Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer.

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients' prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

Inducing endoplasmic reticulum stress in cancer cells using graphene oxide-based nanoparticles.

The endoplasmic reticulum is one of the vital organelles primarily involved in protein synthesis, folding, and transport and lipid biosynthesis. However, in cancer cells its functions are dysregulated leading to ER stress. ER stress is now found to be closely associated with hallmarks of cancer and has subsequently emerged as an alluring target in cancer therapy. However, specific targeting of the ER in a cancer cell milieu remains a challenge. To address this, in this report we have engineered ER-targeted self-assembled 3D spherical graphene oxide nanoparticles (ER-GO-NPs) encompassing dual ER stress inducers, doxorubicin and cisplatin. DLS, FESEM and AFM techniques revealed that the nanoparticles were spherical in shape with a sub 200 nm diameter. Confocal microscopy confirmed the specific homing of these ER-GO-NPs into the subcellular ER within 3 h. A combination of gel electrophoresis, confocal microscopy and flow cytometry studies revealed that these ER-GO-NPs induced ER stress mediated apoptosis in HeLa cells. Interestingly, the nanoparticles also activated autophagy which was inhibited through the cocktail treatment with ER-GO-NPs and chloroquine (CQ). At the same time these ER-GO-NPs were found to be efficient in prompting ER stress associated apoptosis in breast, lung and drug resistant triple negative breast cancer cell lines as well. We envision that these ER specific self-assembled graphene oxide nanoparticles can serve as a platform to exploit ER stress and its associated unfolded protein response (UPR) as a target resulting in promising therapeutic outcomes in cancer therapy.