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1.
Br J Cancer ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750113

ABSTRACT

BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs. RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length. CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.

2.
Anticancer Res ; 44(4): 1377-1387, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38537976

ABSTRACT

BACKGROUND/AIM: Adoptive cell therapy using antigen-specific T cells is a promising treatment modality for cancer patients. Various methods to isolate specific T cells and identify corresponding T cell receptor (TCR) sequences are known. This study aimed to identify antigen-specific TCR from T cells isolated using carboxyfluorescein succinimidyl ester (CFSE), which marks proliferating activated T cells. MATERIALS AND METHODS: CFSE stained healthy donor peripheral blood mononuclear cells (PBMCs) were treated with cytomegalovirus (CMV) or Epstein-Barr virus (EBV) peptides for seven days. Then, proliferating T cells with decreased CFSE staining were isolated and single cell VDJ sequencing was performed on isolated T cells to identify antigen-specific TCRs. RESULTS: As antigen-specific TCR candidates, ten TCR clones were selected for the CMV antigen and five for the EBV antigen. The reactivity of ten CMV TCR-transduced T cells and one EBV TCR-transduced T cell toward T2 cells pulsed with CMV or EBV peptide was confirmed via NFAT-luciferase, IFN-γ ELISA, and cytotoxicity assays. CONCLUSION: Identification of antigen-specific TCRs with CFSE staining is a valid method for the development of effective immunotherapy. The identified CMV- or EBV-specific TCRs can be used for adoptive cell therapy to treat cancer.


Subject(s)
Cytomegalovirus Infections , Epstein-Barr Virus Infections , Fluoresceins , Neoplasms , Succinimides , Humans , T-Lymphocytes , Epstein-Barr Virus Infections/therapy , Herpesvirus 4, Human , Leukocytes, Mononuclear , Cytomegalovirus , Receptors, Antigen, T-Cell
3.
Article in English | MEDLINE | ID: mdl-38242527

ABSTRACT

BACKGROUND: The utilization of short humeral stems in reverse total shoulder arthroplasty has gained attention in recent times. However, concerns regarding the risk of misalignment during implant insertion are associated with their use. METHODS: Eight fresh-frozen cadaveric shoulders were prepared for dissection and biomechanical testing. A bespoke humeral implant was fabricated to facilitate assessment of neutral, varus, and valgus alignments using a single stem, and 10° was established as the maximum permissible angle for misalignments. Shift in humerus position and changes in deltoid length attributable to misalignments relative to the neutral position were evaluated using a Microscribe 3DLx system. The impingement-free range of motion, encompassing abduction, adduction, internal rotation, and external rotation (ER), was gauged using a digital goniometer. The capacity for abduction was evaluated at maximal abduction angles under successive loading on the middle deltoid. A specialized traction system coupled with a force transducer was employed to measure anterior dislocation forces. RESULTS: Relative to the neutral alignment, valgus alignment resulted in a more distal (10.5 ± 2.4 mm) and medial (8.3 ± 2.2 mm) translation of the humeral component, whereas the varus alignment resulted in the humerus shifting more superiorly (11.2 ± 1.3 mm) and laterally (9.9 ± 0.9 mm) at 0° abduction. The valgus alignment exhibited the highest abduction angle than neutral alignment (86.2°, P < .001). Conversely, the varus alignment demonstrated significantly higher adduction (18.4 ± 7.4°, P < .001), internal rotation (68.9 ± 15.0°, P = .014), and ER (45.2 ± 10.5°, P = .002) at 0° abduction compared to the neutral alignments. Anterior dislocation forces were considerably lower (23.8 N) in the varus group compared to the neutral group at 0°ER (P = .047). Additionally, abduction capability was markedly higher in varus alignment at low deltoid loads than the neutral alignment (5N, P = .009; 7.5 N, P = .007). CONCLUSIONS: The varus position enhances rotational range of motion (ROM) but increases instability, while the valgus position does not significantly impact ROM or instability compared to the neutral position.

4.
PLoS One ; 18(8): e0289627, 2023.
Article in English | MEDLINE | ID: mdl-37540709

ABSTRACT

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. Specimens were evaluated by immunohistochemical examination of cyclooxygenase-2, endoplasmic reticulum stress markers, and autophagy markers expression using tissue microarrays. Cyclooxygenase-2 was overexpressed in 29.8% and 23.9% of cases in cohorts 1 and 2, respectively; and it was positively correlated with two out of three endoplasmic reticulum stress-associated molecules (XBP1, p = 0.025 and p = 0.003 in cohort 1 and cohort 2, respectively; PERK, p < 0.001 in both cohorts). Cyclooxygenase-2 was also positively correlated with two out of three autophagy markers (p62, p = 0.002 and p = 0.003 in cohort 1 and cohort 2, respectively; beclin1, p < 0.001 in both cohorts). Although cyclooxygenase-2 was not an independent prognostic factor for distant metastasis free survival and overall survival, its expression was associated with the expression of endoplasmic reticulum stress and autophagy molecules in triple-negative breast cancer.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Apoptosis , Autophagy , Cyclooxygenase 2/genetics , Endoplasmic Reticulum Stress , Oxidative Stress , Triple Negative Breast Neoplasms/genetics
5.
Adv Mater ; 35(40): e2300812, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37357903

ABSTRACT

Immune therapeutics holds great promise in the treatment of type 1 diabetes (T1D). Nonetheless, their progress is hampered by limited efficacy, equipoise, or issues of safety. To address this, a novel and specific nanodelivery platform for T1D that targets high endothelial venules (HEVs) presented in the pancreatic lymph nodes (PLNs) and pancreas is developed. Data indicate that the pancreata of nonobese diabetic (NOD) mice and patients with T1D are unique in their expression of newly formed HEVs. Anti-CD3 mAb is encapsulated in poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles (NPs), the surfaces of which are conjugated with MECA79 mAb that recognizes HEVs. Targeted delivery of these NPs improves accumulation of anti-CD3 mAb in both the PLNs and pancreata of NOD mice. Treatment of hyperglycemic NOD mice with MECA79-anti-CD3-NPs results in significant reversal of T1D compared to those that are untreated, treated with empty NPs, or provided free anti-CD3. This effect is associated with a significant reduction of T effector cell populations in the PLNs and a decreased production of pro-inflammatory cytokine in the mice treated with MECA79-anti-CD3-NPs. In summary, HEV-targeted therapeutics may be used as a means by which immune therapeutics can be delivered to PLNs and pancreata to suppress autoimmune diabetes effectively.


Subject(s)
Diabetes Mellitus, Type 1 , Humans , Mice , Animals , Diabetes Mellitus, Type 1/drug therapy , Mice, Inbred NOD , Pancreas
6.
Sensors (Basel) ; 23(8)2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37112347

ABSTRACT

This paper presents a benchmark analysis of NVIDIA Jetson platforms when operating deep learning-based 3D object detection frameworks. Three-dimensional (3D) object detection could be highly beneficial for the autonomous navigation of robotic platforms, such as autonomous vehicles, robots, and drones. Since the function provides one-shot inference that extracts 3D positions with depth information and the heading direction of neighboring objects, robots can generate a reliable path to navigate without collision. To enable the smooth functioning of 3D object detection, several approaches have been developed to build detectors using deep learning for fast and accurate inference. In this paper, we investigate 3D object detectors and analyze their performance on the NVIDIA Jetson series that contain an onboard graphical processing unit (GPU) for deep learning computation. Since robotic platforms often require real-time control to avoid dynamic obstacles, onboard processing with a built-in computer is an emerging trend. The Jetson series satisfies such requirements with a compact board size and suitable computational performance for autonomous navigation. However, a proper benchmark that analyzes the Jetson for a computationally expensive task, such as point cloud processing, has not yet been extensively studied. In order to examine the Jetson series for such expensive tasks, we tested the performance of all commercially available boards (i.e., Nano, TX2, NX, and AGX) with state-of-the-art 3D object detectors. We also evaluated the effect of the TensorRT library to optimize a deep learning model for faster inference and lower resource utilization on the Jetson platforms. We present benchmark results in terms of three metrics, including detection accuracy, frame per second (FPS), and resource usage with power consumption. From the experiments, we observe that all Jetson boards, on average, consume over 80% of GPU resources. Moreover, TensorRT could remarkably increase inference speed (i.e., four times faster) and reduce the central processing unit (CPU) and memory consumption in half. By analyzing such metrics in detail, we establish research foundations on edge device-based 3D object detection for the efficient operation of various robotic applications.

7.
Bioeng Transl Med ; 8(1): e10273, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36684105

ABSTRACT

Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer-melanoma, breast cancer, and lung cancer-with CLC-PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC-PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC-based drug-conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients.

8.
Nephrol Dial Transplant ; 38(6): 1385-1396, 2023 05 31.
Article in English | MEDLINE | ID: mdl-35945647

ABSTRACT

Kidney diseases represent a major public health problem, affecting millions of people worldwide. Moreover, the treatment of kidney diseases is burdened by the problematic effects of conventional drug delivery, such as systemic drug toxicity, rapid drug clearance, and the absence of precise targeting of the kidney. Although the use of nanotechnology in medicine is in its early stage and lacks robust translational studies, nanomedicines have already shown great promise as novel drug-delivery systems for the treatment of kidney disease. On the basis of our current knowledge of renal anatomy and physiology, pathophysiology of kidney diseases, and physicochemical characteristics of nanoparticles, an expansive repertoire and wide use of nanomedicines could be developed for kidney diseases in the near future. Some limitations have slowed the transition of these agents from preclinical studies to clinical trials, however. In this review, we summarize the current knowledge on renal drug-delivery systems and recent advances in renal cell targeting; we also demonstrate their important potential as future paradigm-shifting therapies for kidney diseases.


Subject(s)
Kidney Diseases , Humans , Kidney Diseases/drug therapy , Drug Delivery Systems , Nanomedicine , Pharmaceutical Preparations , Kidney
9.
J Clin Invest ; 132(24)2022 12 15.
Article in English | MEDLINE | ID: mdl-36519543

ABSTRACT

The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance.


Subject(s)
CD40 Ligand , Graft Survival , Mice , Animals , Mice, Inbred BALB C , Mice, Inbred C57BL , Lymph Nodes , Sirolimus/pharmacology
10.
Article in English | MEDLINE | ID: mdl-36078697

ABSTRACT

Education using humanoid robots can have a positive impact in many fields, including in medical or physical training. This study investigated the effects of robot interactions with respect to facial expressions, gestures, voices and their combinations on the education of the elderly regarding information and communications technology (ICT) from functional and emotional perspectives. In this study, the robot's interaction methods were divided into four categories: (1) voice, (2) voice and expression, (3) voice and gesture, and (4) voice and expression and gesture. An experiment involving an educational application with a humanoid robot was conducted with a total of 15 elderly people over the age of 60. The effect of the humanoid robot's interaction method on education was identified by means of subjective survey evaluation and practice performance data analysis, including error rate, task success rate, and number of retrainings. Through the experiment, functional and emotional aspects of effects were measured. The results showed that performance and perceived effectiveness were not significantly affected by the type of robot interaction, but the degree to which the robot felt like it had emotions, the degree to which the robot felt like a human, and the degree to which the robot was friendly were significantly different according to the interaction type employed by the humanoid robot. The best effect was achieved when voice and gesture were used together during tutoring. Recognizing that ICT education using humanoid robots increases interest and participation in education, such robots are concluded to be a suitable method for performing ICT education. In addition, when designing robotic interactions, the use of the robot's voice and gestures together is expected to lead to greater anthropomorphism, resulting in a stronger relationship with humanoid robots.


Subject(s)
Robotics , Aged , Emotions , Facial Expression , Humans , Robotics/methods
11.
Sci Adv ; 8(24): eabo4271, 2022 06 17.
Article in English | MEDLINE | ID: mdl-35704572

ABSTRACT

Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD+, is up-regulated in CD8+ T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8+ T cell-targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.


Subject(s)
Lupus Erythematosus, Systemic , Virus Diseases , Animals , CD8-Positive T-Lymphocytes/metabolism , Humans , Lupus Erythematosus, Systemic/metabolism , Mice , Mitochondria , Mitophagy , Virus Diseases/metabolism
12.
Nano Today ; 362021 Feb.
Article in English | MEDLINE | ID: mdl-33391389

ABSTRACT

Cancer patients with malignant involvement of tumor-draining lymph nodes (TDLNs) and distant metastases have the poorest prognosis. A drug delivery platform that targets the primary tumor, TDLNs, and metastatic niches simultaneously, remains to be developed. Here, we generated a novel monoclonal antibody (MHA112) against peripheral node addressin (PNAd), a family of glycoproteins expressed on high endothelial venules (HEVs), which are present constitutively in the lymph nodes (LNs) and formed ectopically in the tumor stroma. MHA112 was endocytosed by PNAd-expressing cells, where it passed through the lysosomes. MHA112 conjugated antineoplastic drug Paclitaxel (Taxol) (MHA112-Taxol) delivered Taxol effectively to the HEV-containing tumors, TDLNs, and metastatic lesions. MHA112-Taxol treatment significantly reduced primary tumor size as well as metastatic lesions in a number of mouse and human tumor xenografts tested. These data, for the first time, indicate that human metastatic lesions contain HEVs and provide a platform that permits simultaneous targeted delivery of antineoplastic drugs to the three key sites of primary tumor, TDLNs, and metastases.

13.
Nano Today ; 352020 Dec.
Article in English | MEDLINE | ID: mdl-33244320

ABSTRACT

Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.

14.
Article in English | MEDLINE | ID: mdl-31906363

ABSTRACT

The number of people who complain of sleep disturbances is steadily increasing. An understanding of sleep-related factors is required to address sleep problems. This survey study investigated the sleep habits and sleeping symptoms relating to the comfort and support characteristics of pillows and the relationship between sleep quality and pillow design factors. The study utilized data from 332 participating Korean adults aged 20-76 years (mean age ± SD: males, 40.4 ± 15.2; females, 42.9 ± 15.4). We developed a questionnaire that evaluated sleep habits (sleep duration, bedtime, wake-up time and sleeping position); sleeping symptoms (snoring or coughing, breathing and sleepiness during waking hours) based on the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) questionnaire; and pillow-related factors (support, comfort, fatigue, height and shape) from existing pillow studies. The average sleep duration was 6.8 h, with more than half (52%) of participants sleeping in the supine position. The overall score for sleep quality was considered poor (4.84 points on a seven-point Likert scale), with some degree of sleepiness during waking hours (4.4 points on a seven-point Likert scale). Females went to bed earlier than males and were more likely to sleep in the lateral position compared to males. The number of toss and turn or waking events during sleep increased with age, and older individuals went to sleep earlier and woke up earlier. Among the symptoms of fatigue, pain, discomfort with changing position, snoring, coughing and breathing discomfort, participants reported their highest levels of discomfort due to sleepiness after waking, and they experienced the least head pain. Participants who used a regular-type pillow had poorer satisfaction on multiple comfort and support factors (support, comfort, height suitability, shape suitability) compared with those who used a functional-type pillow. Less head fatigue, less neck fatigue and less shoulder pain had significant effects on sleep quality. To reduce neck fatigue and shoulder pain, designers should consider the height for neck support in the lateral position. To reduce neck fatigue, it is desirable to use materials like latex or memory foam that provide neck support, which can improve sleep quality. The findings of this study contribute to a better understanding of sleep habits and characteristics of pillow comfort and provide practical guidelines for better pillow designs.


Subject(s)
Bedding and Linens , Sleep , Surveys and Questionnaires , Adult , Aged , Bedding and Linens/standards , Cough , Fatigue , Female , Head , Headache , Humans , Male , Middle Aged , Neck , Republic of Korea , Shoulder Pain , Sleep Wake Disorders , Snoring , Young Adult
15.
ACS Nano ; 13(11): 12393-12407, 2019 11 26.
Article in English | MEDLINE | ID: mdl-31518498

ABSTRACT

Inflammation occurring within the transplanted organ from the time of harvest is an important stimulus of early alloimmune reactivity and promotes chronic allograft rejection. Chronic immune-mediated injury remains the primary obstacle to the long-term success of organ transplantation. However, organ transplantation represents a rare clinical setting in which the organ is accessible ex vivo, providing an opportunity to use nanotechnology to deliver therapeutics directly to the graft. This approach facilitates the directed delivery of immunosuppressive agents (ISA) to target local pathogenic immune responses prior to the transplantation. Here, we have developed a system of direct delivery and sustained release of mycophenolate mofetil (MMF) to treat the donor organ prior to transplantation. Perfusion of a donor mouse heart with MMF-loaded PEG-PLGA nanoparticles (MMF-NPs) prior to transplantation abrogated cardiac transplant vasculopathy by suppressing intragraft pro-inflammatory cytokines and chemokines. Our findings demonstrate that ex vivo delivery of an ISA to donor organs using a nanocarrier can serve as a clinically feasible approach to reduce transplant immunity.


Subject(s)
Drug Delivery Systems/methods , Nanomedicine/methods , Transplants , Animals , Female , Graft Rejection/physiopathology , Graft Rejection/prevention & control , Heart Transplantation , Human Umbilical Vein Endothelial Cells , Humans , Inflammation/physiopathology , Inflammation/prevention & control , Male , Mice , Mice, Inbred C57BL , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/pharmacokinetics , Mycophenolic Acid/pharmacology , Nanoparticles/chemistry , Preoperative Care , Transplants/blood supply , Transplants/metabolism , Transplants/physiopathology
16.
J Mater Chem B ; 6(20): 3235-3239, 2018.
Article in English | MEDLINE | ID: mdl-30420913

ABSTRACT

Smart gold nanoparticle-stabilized microbubbles (SAuMBs) composed of a gas-filled core and shell including smart gold nanoparticles (SAuNPs) which can be aggregated in tumors were applied as ultrasound-mediated cancer theranostics. The gas core in the microstructure enabled the detection of tumors using ultrasound and facilitated the delivery of SAuNPs by sonoporation. The SAuNPs spontaneously aggregated in tumors, which allowed photoacoustic (PA) monitoring and photothermal treatment (PTT) of tumors.

17.
Adv Healthc Mater ; 7(14): e1800252, 2018 07.
Article in English | MEDLINE | ID: mdl-29862653

ABSTRACT

Adding value to the intrinsic properties of quantum dots (QDs), a strategy to conjugate dyes on the surface of QDs offers new opportunities, since the coupling between QD and dyes can be designed to allow Förster resonance energy transfer (FRET) and/or electron transfer (eT). These processes are accompanied by the change of QD and/or dye fluorescence and subsequent photochemical reactions (e.g., generation of 1 O2 ). Based on the change of fluorescence signals by the interaction with biomolecules, QD-dye conjugates are exploited as biosensors for the detection of pH, O2 , nicotinamide adenine dinucleotide (phosphate), ions, proteases, glutathione, and microRNA. QD-dye conjugates also can be modulated by the irradiation of external light; this concept is demonstrated for fluorescence super-resolution imaging as photoactivatable or photoswitchable probes. When QDs are conjugated with photosensitizing dyes, the QD-dye conjugates can generate 1 O2 in a repetitive manner for better cancer treatment, and can also be available for approaches using two-photon excitation or bioluminescence resonance energy transfer mechanisms for deep tissue imaging. Here, the recent advances in QD-dye conjugates, where FRET or eT produces fluorescence readouts or photochemical reactions, are reviewed. Various QD-dye conjugate systems and their biosensing/imaging and photodynamic therapeutics are summarized.


Subject(s)
Biosensing Techniques/methods , Quantum Dots , Fluorescence Resonance Energy Transfer , Glutathione/chemistry , Humans , Hydrogen-Ion Concentration , NAD/chemistry
18.
J Am Chem Soc ; 139(22): 7603-7615, 2017 06 07.
Article in English | MEDLINE | ID: mdl-28493679

ABSTRACT

Photoswitching or modulation of quantum dots (QDs) can be promising for many fields that include display, memory, and super-resolution imaging. However, such modulations have mostly relied on photomodulations of conjugated molecules in QD vicinity, which typically require high power of high energy photons at UV. We report a visible light-induced facile modulation route for QD-dye conjugates. QD crystal violets conjugates (QD-CVs) were prepared and the crystal violet (CV) molecules on QD quenched the fluorescence efficiently. The fluorescence of QD-CVs showed a single cycle of emission burst as they go through three stages of (i) initially quenched "off" to (ii) photoactivated "on" as the result of chemical change of CVs induced by photoelectrons from QD and (iii) back to photodarkened "off" by radical-associated reactions. Multicolor on-demand photopatterning was demonstrated using QD-CV solid films. QD-CVs were introduced into cells, and excitation with visible light yielded photomodulation from "off" to "on" and "off" by nearly ten fold. Individual photoluminescence dynamics of QD-CVs was investigated using fluorescence correlation spectroscopy and single QD emission analysis, which revealed temporally stochastic photoactivations and photodarkenings. Exploiting the stochastic fluorescence burst of QD-CVs, simultaneous multicolor super-resolution localizations were demonstrated.

19.
J Nanosci Nanotechnol ; 15(10): 7699-705, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26726397

ABSTRACT

High-efficiency Si solar cells have attracted great attention from researchers, scientists, photovoltaic (PV) industry engineers for the past few decades. With thin wafers, surface passivation becomes necessary to increase the solar cells efficiency by overcoming several induced effects due to associated crystal defects and impurities of c-Si. This paper discusses suitable passivation schemes and optimization techniques to achieve high efficiency at low cost. SiNx film was optimized with higher transmittance and reduced recombination for using as an effective antireflection and passivation layer to attain higher solar cell efficiencies. The higher band gap increased the transmittance with reduced defect states that persisted at 1.68 and 1.80 eV in SiNx films. The thermal stability of SiN (Si-rich)/SiN (N-rich) stacks was also studied. Si-rich SiN with a refractive index of 2.7 was used as a passivation layer and N-rich SiN with a refractive index of 2.1 was used for thermal stability. An implied Voc of 720 mV with a stable lifetime of 1.5 ms was obtained for the stack layer after firing. Si-N and Si-H bonding concentration was analyzed by FTIR for the correlation of thermally stable passivation mechanism. The passivation property of spin coated Al2O3 films was also investigated. An effective surface recombination velocity of 55 cm/s with a high density of negative fixed charges (Qf) on the order of 9 x 10(11) cm(-2) was detected in Al2O3 films.

20.
Nanomedicine (Lond) ; 9(13): 2003-22, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25343350

ABSTRACT

Gold nanoparticles (AuNPs) are attractive photothermal agents for cancer therapy because they show efficient local heating upon excitation of surface plasmon oscillations. The strong absorption, efficient heat conversion, high photostability, inherent low toxicity and well-defined surface chemistry of AuNPs contribute to the growing interest in their photothermal therapy (PTT) applications. The facile tunability of gold nanostructures enables engineering of AuNPs for superior near-infrared photothermal efficacy and target selectivity, which guarantee efficient and deep tissue-penetrating PTT with mitigated concerns regarding side effects by nonspecific distributions. This article discusses the current research findings with representative near-infrared-active AuNPs, which include nanoshell, nanorod, nanocage, nanostar, nanopopcorn and nanoparticle assembly systems. AuNPs successfully demonstrate potential for use in PTT, but several hurdles to clinical applications remain, including long-term toxicity and a need for sophisticated control over biodistribution and clearance. Future research directions are discussed, especially regarding the clinical translation of AuNP photosensitizers.


Subject(s)
Gold/therapeutic use , Metal Nanoparticles/therapeutic use , Neoplasms/therapy , Phototherapy , Humans , Nanoshells/therapeutic use , Neoplasms/pathology , Photosensitizing Agents/therapeutic use , Surface Plasmon Resonance , Tissue Distribution
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