A sensitive sandwich-type electrochemical immunosensor using nitrogen-doped graphene/metal-organic framework-derived CuMnCoOx and Au/MXene for the detection of breast cancer biomarker.

In terms of cancer-related deaths among women, breast cancer (BC) is the most common. Clinically, human epidermal growth receptor 2 (HER2) is one of the most commonly used diagnostic biomarkers for facilitating BC cell proliferation and malignant growth. In this study, a disposable gold electrode (DGE) modified with gold nanoparticle-decorated Ti3C2Tx (Au/MXene) was utilized as a sensing platform to immobilize the capturing antibody (Ab1/Au/MXene). Subsequently, nitrogen-doped graphene (NG) with a metal-organic framework (MOF)-derived copper-manganese-cobalt oxide, tagged as NG/CuMnCoOx, was used as a probe to label the detection antibody (Ab2). A sandwich-type immunosensor (NG/CuMnCoOx/Ab2/HER2-ECD /Ab1/Au/MXene/DGE) was developed to quantify HER2-ECD. NG/CuMnCoOx enhances the conductivity, electrocatalytic active sites, and surface area to immobilize Ab2. In addition, Au/MXene facilitates electron transport and captures more Ab1 on its surface. Under optimal conditions, the resultant immunosensor displayed an excellent linear range of 0.0001 to 50.0 ng. mL-1. The detection limit was 0.757 pg·mL-1 with excellent selectivity, appreciable reproducibility, and high stability. Moreover, the applicability for determining HER2-ECD in human serum samples indicates its ability to monitor tumor markers clinically.

Low-False-Alarm-Rate Timing and Duration Estimation of Noisy Frequency Agile Signal by Image Homogeneous Detection and Morphological Signature Matching Schemes.

Frequency hopping spread spectrum (FHSS) applies widely to communication and radar systems to ensure communication information and channel signal quality by tuning frequency within a wide frequency range in a random sequence. An efficient signal processing scheme to resolve the timing and duration signature from an FHSS signal provides crucial information for signal detection and radio band management purposes. In this research, hopping time was first identified by a two-dimensional temporal correlation function (TCF). The timing information was shown at TCF phase discontinuities. To enhance and resolve the timing signature of TCF in a noisy environment, three stages of signature enhancement and morphological matching processes were applied: first, computing the TCF of the FHSS signal and enhancing discontinuities via wavelet transform; second, a dual-diagonal edge finding scheme to extract the timing pattern signature and eliminate mismatching distortion morphologically; finally, Hough transform resolved the agile frequency timing from purified line segments. A grand-scale Monte Carlo simulation of the FHSS signals with additive white Gaussian noise was carried out in the research. The results demonstrated reliable hopping time estimation obtained in SNR at 0 dB and above, with a minimal false detection rate of 1.79%, while the prior related research had an unattended false detection rate of up to 35.29% in such a noisy environment.

Ultrasound Stimulation Potentiates Management of Diabetic Hyperglycemia.

OBJECTIVE: Glucose homeostasis is the only way to manage diabetic progression as all medications used do not cure diabetes. This study was aimed at verifying the feasibility of lowering glucose with non-invasive ultrasonic stimulation. METHODS: The ultrasonic device was homemade and controlled via a mobile application on the smartphone. Diabetes was induced in Sprague-Dawley rats through high-fat diets followed by streptozotocin injection. The treated acupoint CV12 was at the middle of the xiphoid and umbilicus of the diabetic rats. Parameters of ultrasonic stimulation were an operating frequency of 1 MHz, pulse repetition frequency of 15 Hz, duty cycle of 10% and sonication time of 30 min for a single treatment. DISCUSSION: The diabetic rats exhibited a significant decrease of 11.5% ± 3.6% in blood glucose in 5 min of ultrasonic stimulation (p < 0.001). After the single treatment on the first day, third day and fifth day in the first week, the treated diabetic rats had a significantly small area under the curve of the glucose tolerance test (p < 0.05) compared with the untreated diabetic rats in the sixth week. Hematological analyses indicated that the serum concentrations of ß-endorphin were significantly increased by 58% ± 71.9% (p < 0.05) and the insulin level was increased by 56% ± 88.2% (p = 0.15) without statistical significance after a single treatment. CONCLUSION: Therefore, non-invasive ultrasound stimulation at an appropriate dose can produce a hypoglycemic effect and improve glucose tolerance for glucose homeostasis and may play a role as adjuvant therapy with diabetic medications in the future.

Application of aminobenzoic acid electrodeposited screen-printed carbon electrode in the beta-amyloid electrochemical impedance spectroscopy immunoassay.

Alzheimer's disease (AD) is one of the important neurodegenerative diseases, in the modern aging society, it has become an issue people need to work on. Of the pathogenic factor which leads to AD, beta-amyloid (Aß) is the most important one. It can form the senile plaque which aggregates in the neuron and interrupts the signal transmission. This research is based on the electrochemical system and screen-printed carbon electrode (SPCE) incorporated with pretreatment, electrodeposition, electrochemical impedance spectroscopy (EIS), antibody, and blocking agent. This immunosensor is applied to detect the different concentrations of Aß. The standard curve between electrical impedance and concentration of Aß is calculated. The specificity of the immunosensor is tested. This survey optimizes the electrodeposition condition for 4-aminobenzoic acid (4-ABA) and the parameter for antibody and blocking agents. This study fabricates a more dense, uniform, and stable film of 4-ABA. This sensor presents a range of detection from 1 fg/ml to 100 pg/ml and a limit of detection to 3.84 fg/ml. This sensor can identify the isoform of Aß. This research shortens the fabricating time to 3.5 h. This study fabricates a label-free and low-cost immunosensor for Aß with a short fabricating time, high stability, wide range of detection, low limit of detection, and good specificity. The impedance of the carbon printed electrodes is very high and is always measured by its current but this study provides a fabrication technique for high-efficiency carbon printed electrodes for electrochemical impedance spectroscopy sensing.

Using convolutional neural network to analyze brain MRI images for predicting functional outcomes of stroke.

Nowadays, the physicians usually predict functional outcomes of stroke based on clinical experiences and big data, so we wish to develop a model to accurately identify imaging features for predicting functional outcomes of stroke patients. Using magnetic resonance imaging of ischemic and hemorrhagic stroke patients, we developed and trained a VGG-16 convolutional neural network (CNN) to predict functional outcomes after 28-day hospitalization. A total of 44 individuals (24 men and 20 women) were recruited from Taoyuan General Hospital and China Medical University Hsinchu Hospital to enroll in the study. Based on "modified Rankin Scale (mRS)" and "National Institutes of Health Stroke Scale (NIHSS)" assessments, men, women, and mixed men and women were trained separately to evaluate the differences of the results, and we have shown that VGG-16 demonstrated high accuracy in predicting the functional outcomes of stroke patients. The new deep-learning approach has provided an automated decision support system for personalized recommendations and treatments, assisting the physicians to predict functional outcomes of stroke patients in clinical practice.

Rapid Drug-Screening Platform Using Field-Effect Transistor-Based Biosensors: A Study of Extracellular Drug Effects on Transmembrane Potentials.

Ion channel-modulating drugs play an important role in treating cardiovascular diseases. Facing the demands for continuous monitoring of drug effectiveness, the conventional techniques have become limited when investigating a long-term cellular physiology. To address the challenge, we propose a drug-screening platform using the stretch-out electrical double layer (EDL)-gated field-effect transistor-based biosensors (BioFETs). In this work, BioFETs were utilized to amplify electrophysiological signals from the mammalian cardiomyocytes (H9c2). The stretch-out configuration avoided a chemical corrosion on FETs and prolonged the lifetime of a BioFET system. A physical model is presented to elucidate the signal response to a drug effect on a cell. Fibronectin and gelatin were coated on sensors and served as the adhesive layers where H9c2 cells attached. BioFETs demonstrated an ability to qualitatively distinguish a depolarization and a polarization of the cytomembranes. The signal responses to the changes of transmembrane potentials were monitored in real-time, and they were highly correlated. The effects of nifedipine and calcium ions on cellular electrophysiology were examined and discussed. Due to the capability of a rapid detection, a prolonged lifetime, and an excellent sensitivity to an electrical change, a stretch-out EDL-gated BioFET can be a drug-screening platform for ion channel modulators.

Flexible Optogenetic Transducer Device for Remote Neuron Modulation Using Highly Upconversion-Efficient Dendrite-Like Gold Inverse Opaline Structure.

A remote optogenetic device for analyzing freely moving animals has attracted extensive attention in optogenetic engineering. In particular, for peripheral nerve regions, a flexible device is needed to endure the continuous bending movements of these areas. Here, a remote optogenetic optical transducer device made from a gold inverse opaline skeleton grown with a dendrite-like gold nanostructure (D-GIOF) and chemically grafted with upconversion nanoparticles (UCNPs) is developed. This implantable D-GIOF-based transducer device can achieve synergistic interaction of the photonic crystal effect and localized surface plasmon resonance, resulting in considerable UCNP conversion efficiency with a negligible thermal effect under low-intensity 980 nm near-infrared (NIR) light excitation. Furthermore, the D-GIOF-based transducer device exhibits remarkable emission power retention (≈100%) under different bending states, indicating its potential for realizing peripheral nerve stimulation. Finally, the D-GIOF-based transducer device successfully stimulates neuronal activities of the sciatic nerve in mice. This study demonstrates the potential of the implantable device to promote remote NIR stimulation for modulation of neural activity in peripheral nerve regions and provides proof of concept for its in vivo application in optogenetic engineering.

High-Sensitivity and Trace-Amount Specimen Electrochemical Sensors for Exploring the Levels of ß-Amyloid in Human Blood and Tears.

As the occurrence of Alzheimer's disease (AD) has increased, the detection and treatment of AD have become global social issues. Effective early detection and wide-range screening of AD allow patients to gain early control and delay brain degeneration. For these reasons, we choose electrochemical sensors to complete the detection task. Although bio-electrochemical technology for antibody and antigen sensing is not a new technology, considering the scarcity of tear samples for dementia and since the existing AD detection techniques are highly invasive and expensive for subjects, we have to use the traditional detection techniques for the early screening of Alzheimer's disease via trace-amount specimens. An AD-related protein in the eye is thought to be an important biomarker for early detection. To carry out detection using tear samples as a test specimens, a tear collection device was developed in this study that extracted 10 µL of tear fluid from a tear Schirmer strip. In this research, we distinguished healthy people in different age groups and detect Aß in both tear and blood samples. We developed a biosensor, which could detect Aß in tear specimen from 1 to 100 pg/mL. Also, this biosensor is inexpensive, disposable, and easy to use. In our result, the concentration of Aß in tears was approximately 10 times more than that in blood. This study demonstrates the feasibility and prospects of future screening for AD-associated biomarkers by a dynamic comparison between blood and tears.

Highly sensitive FET sensors for cadmium detection in one drop of human serum with a hand-held device and investigation of the sensing mechanism.

As the heavy metal contamination is becoming worse, monitoring the heavy metal content in water or human body gets more and more important. In this research, a cadmium ion-selective field effect transistor (Cd-ISFET) for rapidly detecting cadmium ions has been developed and the mechanism of the sensor is also investigated in depth. Our Cd-ISFET sensor exhibits high sensitivity beyond the ideal Nernst sensitivity, wide dynamic range, low detection limit (∼10-11M), which is comparable with inductively coupled plasma mass spectrometry, and easy operation enabling people to detect cadmium ion by themselves. From the analysis of electrical measurement results, this Cd-ISFET is preferred to operate at the bias with the maximum transconductance of the FET to enhance the sensor signal. The AC impedance measurement is carried out to directly investigate the mechanism of an ion-selective membrane (ISM). From impedance results, the real part of the total impedance, which is the resistance, was shown to dominate the sensor signal. The potential drop across the ISM is caused by the heavy metal ion in the membrane, which is employed to the gate of the FET via an extended gate electrode. Cadmium ion detection in one drop of human serum with this sensor was demonstrated. This cost-effective and highly sensitive sensor is promising and can be used by anyone and anywhere to prevent people from cadmium poisoning.

Enhancement of Neurite Outgrowth by Warming Biomaterial Ultrasound Treatment.

Ultrasound is a method for enhancing neurite outgrowth because of its thermal effect. In order to reach the working temperature to enhance neurite outgrowth, long-time treatment by ultrasound is necessary, while acknowledging that the treatment poses a high risk of damaging nerve cells. To overcome this problem, we developed a method that shortens the ultrasonic treatment time with a warming biomaterial. In this study, we used Fe3O4 nanoparticle-embedded polycaprolactone (PCL) as a sonosensitized biomaterial, which has an excellent heating rate due to its high acoustic attenuation. With this material, the ultrasonic treatment time for enhancing neurite outgrowth could be effectively shortened. Ultrasonic treatment could also increase neuronal function combined with the warming biomaterial, with more promoter neuronal function than only ultrasound. Moreover, the risk of overexposure can be avoided by the use of the warming biomaterial by reducing the ultrasonic treatment time, providing better effectiveness.

Progress in Polymeric Nano-Medicines for Theranostic Cancer Treatment.

Cancer is a life-threatening disease killing millions of people globally. Among various medical treatments, nano-medicines are gaining importance continuously. Many nanocarriers have been developed for treatment, but polymerically-based ones are acquiring importance due to their targeting capabilities, biodegradability, biocompatibility, capacity for drug loading and long blood circulation time. The present article describes progress in polymeric nano-medicines for theranostic cancer treatment, which includes cancer diagnosis and treatment in a single dosage form. The article covers the applications of natural and synthetic polymers in cancer diagnosis and treatment. Efforts were also made to discuss the merits and demerits of such polymers; the status of approved nano-medicines; and future perspectives.

Improving the reproducibility, accuracy, and stability of an electrochemical biosensor platform for point-of-care use.

Electrochemical biosensors possess numerous desirable qualities for target detection, such as portability and ease of use, and are often considered for point-of-care (POC) development. Label-free affinity electrochemical biosensors constructed with semiconductor manufacturing technology (SMT)-produced electrodes and a streptavidin biomediator currently display the highest reproducibility, accuracy, and stability in modern biosensors. However, such biosensors still do not meet POC guidelines regarding these three characteristics. The purpose of this research was to resolve the limitations in reproducibility and accuracy caused by problems with production of the biosensors, with the aim of developing a platform capable of producing devices that exceed POC standards. SMT production settings were optimized and bioreceptor immobilization was improved through the use of a unique linker, producing a biosensor with exceptional reproducibility, impressive accuracy, and high stability. Importantly, the three characteristics of the sensors produced using the proposed platform all meet POC standards set by the Clinical and Laboratory Standards Institute (CLSI). This suggests possible approval of the biosensors for POC development. Furthermore, the detection range of the platform was demonstrated by constructing biosensors capable of detecting common POC targets, including circulating tumor cells (CTCs), DNA/RNA, and curcumin, and the devices were optimized for POC use. Overall, the platform developed in this study shows high potential for production of POC biosensors.

Label-Free Impedimetric Immunosensors Modulated by Protein A/Bovine Serum Albumin Layer for Ultrasensitive Detection of Salbutamol.

The sensing properties of immunosensors are determined not only by the amount of immobilized antibodies but also by the number of effective antigen-binding sites of the immobilized antibody. Protein A (PA) exhibits a high degree of affinity with the Fc part of IgG antibody to feasibly produce oriented antibody immobilization. This work proposes a simple method to control the PA surface density on gold nanostructure (AuNS)-deposited screen-printed carbon electrodes (SPCEs) by mixing concentration-varied PA and bovine serum albumin (BSA), and to explore the effect of PA density on the affinity attachment of anti-salbutamol (SAL) antibodies by electrochemical impedance spectroscopy. A concentration of 100 µg/mL PA and 100 µg/mL BSA can obtain a saturated coverage on the 3-mercaptoproponic acid (MPA)/AuNS/SPCEs and exhibit a 50% PA density to adsorb the amount of anti-SAL, more than other concentration-varied PA/BSA-modified electrodes. Compared with the randomly immobilized anti-SAL/MPA/AuNS/SPCEs and the anti-SAL/PA(100 µg/mL):BSA(0 µg/mL)/MPA/AuNS/SPCE, the anti-SAL/PA(100 µg/mL): BSA(100 µg/mL)/MPA/AuNS/SPCE-based immunosensors have better sensing properties for SAL detection, with an extremely low detection limit of 0.2 fg/mL and high reproducibility (<2.5% relative standard deviation). The mixture of PA(100 µg/mL):BSA(100 µg/mL) for the modification of AuNS/SPCEs has great promise for forming an optimal protein layer for the oriented adsorption of IgG antibodies to construct ultrasensitive SAL immunosensors.

Correction: Study of near-infrared light-induced excitation of upconversion nanoparticles as a vector for non-viral DNA delivery.

[This corrects the article DOI: 10.1039/D0RA05385F.].

Study of near-infrared light-induced excitation of upconversion nanoparticles as a vector for non-viral DNA delivery.

Clinical requirements have necessitated the development of biomedical nanomaterials that can be implanted into tissues or bodies. Physiological regulation can be achieved in these nanomaterials through external light. The combination of nanomaterials with infrared optics can be termed optogenetics. The low autofluorescence of upconversion nanoparticles (UCNPs) has several applications in the biological field. For optogenetics applications, UCNPs with high fluorescence performance and photostability can solve the penetration depth problem. NaYF4:Yb,Tm nanocrystals with controllable sizes, shapes, and compositions were synthesized using a rapid coprecipitation method in organic solvent. UCNPs using single crystal nanoparticles provide higher chemical stability than those using amorphous phase. However, because UCNPs are usually capped with hydrophobic ligands, it is particularly important to prepare biocompatible UCNPs with specific molecular recognition capabilities. Surface modification and subsequent functionalization are essential for the application of inorganic nanomaterials in the biological environment and are arousing increasing research interest. Due to the high biocompatibility and high loading of materials, mesoporous silica and amine groups were selected as the best candidates. Expression of plasmid DNA in vivo and transfection efficiency were determined by fluorescence microscopy and flow cytometry. The MTT assay was used to evaluate the particle biocompatibility; the results showed that UCNP@mSiO2 has great biocompatibility. Additionally, at neutral pH, the cell surface is negatively charged. Therefore, the surface is functionalized with amino groups and can be electrostatically bound to DNA. Finally, UCNP@mSiO2-NH2 as a vector was applied in live cells by loading DNA; according to the results, DNA-UCNPs were successfully transfected in the primary cells, and NaYF4:Yb,Tm@mSiO2-NH2-DNA were observed to have good transfection efficiency by flow cytometry. It is expected that this work will provide a different method from the traditional adenovirus method and improve the immune response and side effects caused by adenovirus.

The Effects of Different Dynamic Culture Systems on Cell Proliferation and Osteogenic Differentiation in Human Mesenchymal Stem Cells.

The culture environment plays an important role for stem cells' cultivation. Static or dynamic culture preserve differential potentials to affect human mesenchymal stem cells' (hMSCs) proliferation and differentiation. In this study, hMSCs were seeded on fiber disks and cultured in a bidirectional-flow bioreactor or spinner-flask bioreactor with a supplement of osteogenic medium. The hMSCs' proliferation, osteogenic differentiation, and extracellular matrix deposition of mineralization were demonstrated. The results showed that the spinner flask improved cell viability at the first two weeks while the bidirectional-flow reactor increased the cell proliferation of hMSCs through the four-week culture period. Despite the flow reactor having a higher cell number, a lower lactose/glucose ratio was noted, revealing that the bidirectional-flow bioreactor provides better oxygen accessibility to the cultured cells/disk construct. The changes of calcium ions in the medium, the depositions of Ca2+ in the cells/disk constructs, and alkaline phosphate/osteocalcin activities showed the static culture of hMSCs caused cells to mineralize faster than the other two bioreactors but without cell proliferation. Otherwise, cells were distributed uniformly with abundant extracellular matrix productions using the flow reactor. This reveals that the static and dynamic cultivations regulated the osteogenic process differently in hMSCs. The bidirectional-flow bioreactor can be used in the mass production and cultivation of hMSCs for applications in bone regenerative medicine.

Cross-section and feasibility study on the non-invasive evaluation of muscle hemodynamic responses in Duchenne muscular dystrophy by using a near-infrared diffuse optical technique.

Duchenne muscular dystrophy (DMD) is an X-linked debilitating muscular disease that may decrease nitric oxide (NO) production and lead to functional muscular ischemia. Currently, the 6-minute walk test (6-MWT) and the North Star Ambulatory Assessment (NSAA) are the primary outcome measures in clinical trials, but they are severely limited by the subjective consciousness and mood of patients, and can only be used in older and ambulatory boys. This study proposed using functional near-infrared spectroscopy (fNIRS) to evaluate the dynamic changes in muscle hemodynamic responses (gastrocnemius and forearm muscle) during a 6-MWT and a venous occlusion test (VOT), respectively. Muscle oxygenation of the forearm was evaluated non-invasively before, during and after VOT in all participants (included 30 DMD patients and 30 age-matched healthy controls), while dynamic muscle oxygenation of gastrocnemius muscle during 6-MWT was determined in ambulatory participants (n = 18) and healthy controls (n = 30). The results reveal that impaired muscle oxygenation was observed during 6-MWT in DMD patients that may explain why the DMD patients walked shorter distances than healthy controls. Moreover, the results of VOT implied that worsening muscle function was associated with a lower supply of muscle oxygenation and may provide useful information on the relationship between muscular oxygen consumption and supply for the clinical diagnosis of DMD. Therefore, the method of fNIRS with VOT possesses great potential in future evaluations of DMD patients that implies a good feasibility for clinical application such as for monitoring disease severity of DMD.

A feasibility study on non-invasive oxidative metabolism detection and acoustic assessment of human vocal cords by using optical technique.

Voice disorder such as vocal fatigue is a common and complex multifaceted clinical problem that presents a significant impact on quality of life. In this study, the functional near-infrared diffuse optical technique (fNIRS-DOT) was proposed as a novel approach for human vocal cords oxidative metabolism detection and acoustic assessment simultaneously to provide a multidimensional assessment of voice disorder. A totally of 60 healthy subjects included 30 male and 30 female adults of age-matched were recruited and performed a vocal loading task to trigger a mild inflammation of the vocal cords in this study. In the results of oxidative metabolism, the vocal cords expressed hypoxia after vocal loading task in both male and female groups that could provide relevant information on the relationship between tissue oxygen consumption and supply for vocal cords diagnosis. Additionally, the results of optical acoustic assessment revealed the worse/changes voice quality after vocal loading task. Therefore, integration of non-invasive oxidative metabolism detection and acoustic assessment by using optical technique could provide more relevant information for diagnosis of voice disorders. The multi-functional vocal cords detection system could provide a good feasibility for clinical applications such as diagnosis and therapeutic monitoring of voice disorder.

Dielectrophoresis System for Testing Antimicrobial Susceptibility of Gram-Negative Bacteria to ß-Lactam Antibiotics.

Gram-negative bacteria (GNBs) are common pathogens causing severe sepsis. Rapid evaluation of drug susceptibility would guide effective antibiotic treatment and promote life-saving. A total of 78 clinical isolates of 13 Gram-negative species collected between April 2013 and November 2013 from two medical centers in Tainan were tested. Bacterial morphology changes in different concentrations of antibiotics were observed under the electric field of a quadruple electrode array using light microscopy. The minimal inhibitory concentrations (MICs) of four antimicrobial agents, namely, cefazolin, ceftazidime, cefepime, and doripenem, were determined by the dielectrophoretic antimicrobial susceptibility testing (dAST) and by the conventional broth dilution testing (BDT). The antibiotics at the concentration of 1× MIC induced obvious morphological changes in susceptible GNBs, including cell elongation, cell swelling, or lysis, at 90 min. In contrast, resistant strains remained unchanged. The MIC results measured by dAST were in good agreement with those of BDT (essential agreement 95.6%). The category agreement rate was 89.2%, and the very major errors rate for dAST was 2.9%. In conclusion, dAST could accurately determine drug susceptibility within 90 min. Comprehensive tests by dAST for more drugs against more GNB species are possible in the future.

Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.

Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment.