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Objectives The aim of this study was to develop a new material with integrated interface design that could achieve the purpose of environmental-sensing controlled release against cariogenic bacteria. Furthermore, this material can rebalance oral flora and serve as a preventive and reparative measure of dental caries. Materials and Methods NaF@PAA@HA@polyelectrolytes@HA@PAA particles were synthesized using the method of two-solution phases precipitation followed by biocompatible polymers coating layer by layer. The structure of the particles was confirmed by transmission electron microscope. The fluoride release profile was measured by fluoride ion electrode. Antimicrobial activity against the cariogenic microorganisms was analyzed by scanning electron microscopy and energy dispersive spectrum. The efficacy experiments were conducted on tooth enamel slides to evaluated fluoride absorption and antibacterial activity of the prototype toothpaste containing microcube particles Results The structure of NaF@PAA@HA@polyelectrolytes@HA@PAA particles showed a core surrounded by tooth-adhesion polymer layers in thin fin or filament structure. The loaded concentration of fluoride in the particles' core was 148,996 ± 28,484 ppm. NaF@PAA@HA@polyelectrolytes@HA@PAA particles showed selective inhibition of cariogenic microorganisms over probiotic strains and stronger fluoride adhesion on tooth enamel. A burst release (over 80%) of fluoride from the particle-containing toothpaste was observed under cariogenic acidic environment (pH Conclusions In our study, an intelligent toothpaste was developed that selectively inhibits cariogenic bacteria by microenvironment proton-triggered fluoride release. Such novel design would accomplish a favorable flora balance for optimal long-term oral health.

Ovarian cancer (OVCA) is the most fatal gynecological cancer with late diagnosis and chemoresistance being the main obstacles of treatment success. Since there is no reliable approach to diagnosing patients at an early stage as well as predicting chemoresponsiveness, there is the urgent need to develop a diagnostic platform for such purposes. Extracellular vesicles (EVs) present as an attractive biomarker given their potential specificity and sensitivity to tumor sites. We have developed a novel sensor which utilizes cysteine functionalized gold nanoparticles to simultaneously bind to cisplatin (CDDP) and EVs affording us the advantage of predicting OVCA chemoresponsiveness, histologic subtypes, and early diagnosis using surface enhanced Raman spectroscopy. EVs were isolated and characterized from chemosensitive and resistant OVCA cells lines as well as pre-operative patient blood samples. The mechanistic role of plasma gelsolin (pGSN) in EV-mediated CDDP secretion in OVCA chemoresistance was investigated using standard cellular and molecular techniques. We determined that chemoresistant cells secrete significantly higher levels of small EVs (sEVs) and EVs containing CDDP (sEV-CDDP) compared with their sensitive counterparts. pGSN interacted with cortactin (CTTN) and both markers were significantly upregulated in chemoresistant patients’ tumors compared with the sensitive patients. Silencing pGSN decreased EV and EV-CDDP secretions in the resistant cells whereas its over-expression in sensitive cells upregulated EV and EV-CDDP secretion, suggesting the potential role of pGSN in EV-mediated CDDP export. sEV/CA125 ratio outperformed CA125 and sEV individually in predicting early stage, chemoresistance, residual disease, tumor recurrence, and patient survival. These findings highlight pGSN as a potential therapeutic target as well as providing a potential diagnostic platform to detect OVCA earlier and predict chemoresistance; an intervention that will positively impact patients’ survival.

Simultaneous targeting of both the tumor microenvironment and cancer cells by a single nanomedicine has not been reported to date. Here, we report the dual properties of zero-valent-iron nanoparticle (ZVI-NP) to induce cancer-specific cytotoxicity and anti-cancer immunity. Methods: Cancer-specific cytotoxicity induced by ZVI-NP was determined by MTT assay. Mitochondria functional assay, immunofluorescence staining, Western blot, RT-qPCR, and ChIP-qPCR assays were used to dissect the mechanism underlying ZVI-NP-induced ferroptotic cancer cell death. The therapeutic potential of ZVI-NP was evaluated in immunocompetent mice and humanized mice. Immune cell profiles of allografts and ex vivo cultured immune cells were examined by flow cytometry analysis, RT-qPCR assay, and immunofluorescence. Results: ZVI-NP caused mitochondria dysfunction, intracellular oxidative stress, and lipid peroxidation, leading to ferroptotic death of lung cancer cells. Degradation of NRF2 by GSK3/β-TrCP through AMPK/mTOR activation was enhanced in such cancer-specific ferroptosis. In addition, ZVI-NP attenuated self-renewal ability of cancer and downregulated angiogenesis-related genes. Importantly, ZVI-NP augmented anti-tumor immunity by shifting pro-tumor M2 macrophages to anti-tumor M1, decreasing the population of regulatory T cells, downregulating PD-1 and CTLA4 in CD8+ T cells to potentiate their cytolytic activity against cancer cells, while attenuating PD-L1 expression in cancer cells in vitro and in tumor-bearing immunocompetent mice. In particular, ZVI-NPs preferentially accumulated in tumor and lung tissues, leading to prominent suppression of tumor growth and metastasis. Conclusions: This dual-functional nanomedicine established an effective strategy to synergistically induce ferroptotic cancer cell death and reprogram the immunosuppressive microenvironment, which highlights the potential of ZVI-NP as an advanced integrated anti-cancer strategy.

Background: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients.Methods: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome.Results: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis‐diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer.Conclusion: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.

In this study, we demonstrated that zero-valent iron (ZVI), which is widely used to remediate environmental contamination through the production of high-energy reactive oxygen species (ROS), exhibited differential cytotoxicity in cancerous cells and nonmalignant cells. Nanoparticles (NPs) with different shells exhibited distinct potencies against cancerous cells, which depended on their iron-to-oxygen ratios. Silver-coated ZVI NPs (ZVI@Ag) had the highest potency among synthesized ZVI NPs, and they simultaneously exhibited adequate biocompatibility with nonmalignant keratinocytes. The assessment of the intracellular dynamics of iron species revealed that the uptake of ZVI@Ag was similar between cancerous cells and nonmalignant cells during the first 2 h; however, only cancerous cells rapidly converted NPs into iron ions and generated large amounts of intracellular ROS, which was followed by apoptosis and autophagy induction. The aforementioned processes were prevented in the presence of iron ion chelators or by preoxidizing NPs before administration. Neutralization of lysosomal pH effectively reduced ZVI@Ag NP-induced programmed cell death. In the xenograft mouse model, cancer growth was significantly inhibited by a single dose of systematically administered NPs without significant weight loss in animals.

Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of the actin-associated protein cytosolic gelsolin (GSN) regulates the gynecological cancer cell fate resulting in dysregulation in chemosensitivity. In this study, we report that elevated expression of plasma gelsolin (pGSN), a secreted isoform of GSN and expressed from the same GSN gene, correlates with poorer overall survival and relapse-free survival in patients with OVCA. In addition, it is highly expressed and secreted in chemoresistant OVCA cells than its chemosensitive counterparts. pGSN, secreted and transported via exosomes (Ex-pGSN), upregulates HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as confers cisplatin resistance in otherwise chemosensitive OVCA cells. These findings support our hypothesis that exosomal pGSN promotes OVCA cell survival through both autocrine and paracrine mechanisms that transform chemosensitive cells to resistant counterparts. Specifically, pGSN transported via exosomes is a determinant of chemoresistance in OVCA.

Addressing nanomedicine resistance is critical for its ultimate clinical success; despite this, advancing the therapeutic designs for cancer therapy are rarely discussed in the literature. In this study, we discovered that ferroptosis is the central mechanism governing the therapeutic efficacy and resistance of treatment with zero-valent iron nanoparticles (ZVI NPs). In ZVI-sensitive oral cancer cells, ZVI NPs-induced ferroptosis was characterized by mitochondrial lipid peroxidation and reduced levels of glutathione peroxidases (GPx) in subcellular organelles. However, resistant cells could attenuate ZVI-induced oxidative stress and GPx reduction. They also showed stronger mitochondrial respiration ability, thus resisting ZVI NPs-induced mitochondrial membrane potential loss. Transcriptome comparison and quantitative polymerase chain reaction (qPCR) analysis revealed that ZVI-resistant cancer cells expressed a gene set related to enhanced NADPH supply, higher detoxification capacity of reactive oxygen species, and decreased sensitivity to ferroptosis inducers (FINs). Finally, we discovered that certain FINs were able to sensitize ZVI-resistant cancer cells to become treatable without compromising healthy non-malignant cells. These findings suggest that ferroptosis can serve as a druggable target for anti-cancer nanomedicine and therapeutic resistance modulation using ZVI NPs.

A self-driving, thermal-diffusion-based bioassay for the detection of microorganisms in a liquid medium is presented in this paper. In the bioassay, each particle functions as an individual sensing probe. Thus, the representative Brownian velocity of microparticles can be obtained by analyzing the velocity histogram of each particle. The ensemble average was used to enhance peak Brownian velocity. Relative error was reduced to 0.5% when the number of counted particles exceeded 60. The experimentally measured and theoretically derived Brownian velocities and diameters of the particles were in good agreement. The relative standard deviations of the temporal stability and reproducibility of the bioassay were maintained below 1.2%. A calibration curve was constructed and used to distinguish two mixed colloidal suspensions to provide proof that the bioassay can be used in practical applications. The particles were functionalized with antibodies to enable the real biological application of the bioassay in the capture and detection of motile Pseudomonas aeruginosa and nonmotile Staphylococcus aureus. The diffusivity values of both bacterial growth media decreased as bacterial concentration increased. Given that the viscosity of the growth media varied as bacteria proliferated, additional bacteria-free reference particles were added to the medium to provide dynamic background information. The diffusion-based bioassay presented here is easy to use, robust, and highly reliable. In contrast to most existing biosensors, it does not require an external power source and is thus ideal for use in resource-limited areas.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 μg/ml and ∼1 μl, estimated total analyte consumption < 4 pg) within 21 minutes. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.

Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.

The development of a single agent with multifunctionality for the rapid detection and inhibition of the spread of pathogenic microorganisms is of great importance for environmental hygiene as well as water and food safety. For this purpose, we integrate plasmonic nano-Au, near-infrared (NIR)-activated Fe

Real-time quantitative PCR device was emerging to be an essential platform in precision medicine and other genetic testing applications. The traditional heating method is extremely energy and time-consuming. Novel photothermal conversion based mechanism was reported recently that speed up the system to an unprecedented speed and energy efficiency and sensing of the temperature change became a challenging task. In general, the temperature of the reagent in the tubes was determined according to transform equations from the temperature of the heating block. However, the true temperature in each reagent was difficult to be accurately estimated. In this study, we proposed a new optical method to heat the reagent and integrated the thermocouple, metal tape, and thermal conducting rubber to serve as a composite temperature sensor (CTS) for measuring the radiant temperature from the tube. In addition, the temperature of the reagent was also detected by a thermocouple in the reagent. The relationship between the two temperature measurements was compared. The results showed that the CTS with copper tape was more sensitive and stable than that of other groups. A suitable dimension was determined to be 4 x 3 mm for the copper tape with a 1 mm thickness of the thermal conducting rubber. The mathematical correlation between the two measurements was evaluated and turned out to be 96.2 %. In the future, the CTS outside the tube could be applied to estimate the actual temperature of the reagent in the tube in further PCR applications.

The development of a single agent with multifunctionality for the rapid detection and inhibition of the spread of pathogenic microorganisms is of great importance for environmental hygiene as well as water and food safety. For this purpose, we integrate plasmonic nano-Au, near-infrared (NIR)-activated Fe3O4 nanoclusters, and NIR-absorbing polydopamine to form a leukocyte-like Fe3O4@Au nanostructure to treat microorganisms. Through high-temperature reduction of HAuCl4 with L-dopamine, Au atoms are spontaneously generated along with Fe3O4 nanoclusters via a site-selected atom deposition process between the Au(111) and Fe3O4(222) lattice planes. Combining the magnetic properties of Fe3O4 and the optical functionality of gold nanoparticles, the Fe3O4@Au nanohybrid exhibits effective photothermal conversion and magnetism-guided aggregation to improve the molecular surface-enhanced Raman scattering (SERS) signal, achieving a limit of detection on the micromolar to nanomolar level for methylene blue (MB) and 4-aminothiophenol (4-ATP). After magnetism-assisted adsorption, we adopt Escherichia coli (E. coli) as a model analyte and demonstrate label-free SERS sensing of bacterial cell molecular structures based on optical fingerprints and recyclable photothermal ablation of bacterial pathogens (Gram-positive, Gram-negative, and anaerobic bacteria).

Quantitative polymerase chain reaction (qPCR) is the most important quantitative sensing technique for pathogens, especially for emerging pandemics such as the coronavirus outbreak this year. The qPCR chip and device were investigated to meet the unmet needs of ultrafast inspection time, high accuracy, and small system volume. Therein, the fluorescence intensity was the most important signal in qPCR quantification of DNA amplifications, which is essential not only in the confirmative diagnosis of positive or negative infection, but also in the assessment of viral load for therapeutic and quarantine decision making. As the target DNAs got amplified, the interaction of fluorescence dye and double strand DNA will generate fluorescence signal proportional to amplified DNA in the intensity when excited by certain wavelength. A miniature spectro-detector was employed to receive the fluorescence scattering for digital output of the intensity in the qPCR chip in this study, and the optical simulation and actual experimental design and results according to the optical simulation results were performed to study the effect of the stray light shutter (SLS) in the improvement of the signal in fluorescence detection. The analysis results showed that the signal-to-noise ratio (SNR) of the fluorescence can be enhanced significantly for five times of the control using the SLS with a shape of extended component aperture, where the protruding structure was positioned away from the center. The experimental results showed that fluorescence intensity can be enhanced by 15.50% and 9.86% when adding the above shape of SLS in resin- and in glass-based chip, respectively. The results also demonstrated that the optical setup had good stability and repeatability in fluorescence detection, and variation was less than 1.00%. Our results can provide important reference to the development of qPCR chip to obtain the high SNR fluorescence signal in DNA quantification process.

Dar-Bin Shieh is Deputy Minister of The Ministry of Science and Technology (MOST), Taiwan, which supports and promotes innovations in science and technology. Before assuming his current position, Shieh previously occupied roles including; distinguished professor in the College of Medicine at National Cheng Kung University (NCKU); attending physician at NCKU Medical Center; Director of University Development at NCKU; and Founding Chair of the International Institute of Macromolecular Analysis and Nanomedicine Innovations (iMANI). Shieh and the MOST believe that science and technology should be developed for people, responding to society's needs, with a view to promoting the local economy and improving quality of life. The MOST is working towards a long-term national science and technology development roadmap that can assist with national development. The MOST is a proponent of the importance and value of international collaboration and has restructured its funding system to further encourage these collaborations. It also encourages cross-disciplinary collaboration, with a view to sparking innovation. Talent cultivation and recruitment are key challenges in scientific advancement and the MOST has initiated two talent recruitment programmes, including the Einstein and the Columbus programmes, to help encourage, foster and develop scientific talent in Taiwan.

Clostridioides difficile, a spore-forming bacterium, is a nosocomial infectious pathogen which can be found in animals as well. Although various antibiotics and disinfectants were developed, C. difficile infection (CDI) remains a serious health problem. C. difficile spores have complex structures and dormant characteristics that contribute to their resistance to harsh environments, successful transmission and recurrence. C. difficile spores can germinate quickly after being exposed to bile acid and co-germinant in a suitable environment. The vegetative cells produce endospores, and the mature spores are released from the hosts for dissemination of the pathogen. Therefore, concurrent elimination of C. difficile vegetative cells and inhibition of spore germination is essential for effective control of CDI. This review focused on the molecular pathogenesis of CDI and new trends in targeting both spores and vegetative cells of this pathogen, as well as the potential contribution of nanotechnologies for the effective management of CDI.

Professor Dar-Bin Shieh, Deputy Minister at the Taiwan Ministry of Science and Technology, shares with us details of the efforts undertaken at the Ministry to promote and support scientific and technological research and development in Taiwan, including his response to the COVID-19 pandemic.

Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.

Few studies have investigated the effects of iron oxide nanoparticles (NPs) on analgesia. We developed inflammatory pain models via complete Freund's adjuvant injection over the hind paw in CD1 mice. Various doses of magnetite (Fe3O4) NPs were injected into the paw. Analgesia behavior was checked with von Frey microfilament and thermal irradiation measurements. Paw skin tissues were harvested at the maximal analgesia time point. The presence of activated white cells (CD68, myeloperoxidase) and free radical (reactive oxygen species, ROS) production was also checked. Western blotting was used to identify the changes of ROS production enzymes. Fe3O4 NPs demonstrated a dose-related analgesia effect with significant reduction in inflammatory cells, pro-inflammatory markers, and ROS production in the lesion paw. ROS production enzyme expression also declined. The results indicate that local Fe3O4 NP administration induced significant analgesia via attenuation of inflammatory cell infiltration and pro-inflammatory signaling as well as scavenging of microenvironment free radicals in a mouse inflammatory pain model.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by defects in the leukocyte NADP oxidase. We previously reported that sarcoplasmic/endoplasmic reticulum calcium pump (SERCA) inhibitors could be used to rescue mutant H338Y-gp91phox protein of a particular type of CGD with a CybbC1024T mutation, leading to endoplasmic reticulum (ER) retention of the mutant protein. In this study, we developed a novel mouse model with the CybbC1024T mutation on a Cybb knockout background and investigated the therapeutic effects of ER-targeted delivery of the SERCA inhibitor, curcumin, with poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs). We found that PLGA encapsulation improved the efficacy of curcumin as a SERCA inhibitor to induce ER calcium release. ER-targeting curcumin-loaded PLGA NPs reduced and delayed extracellular calcium entry and protected the cells from mitochondrial damage and apoptosis. In vivo studies showed that ER-targeting curcumin-loaded PLGA NPs treatment enhanced neutrophil gp91phox expression, ROS production and peritoneal bacterial clearance ability of the CybbC1024T transgenic Cybb−/− mice. Our findings indicate that ER-targeted delivery of curcumin not only rescues ER-retained H338Y-gp91phox protein, and hence leukocyte function, but also enhances the bioavailability and reduces cytotoxicity. Modulation of ER function by using organelle-targeted NPs may be a promising strategy to improve the therapeutic potential of curcumin as a treatment for CGD.