A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer.

Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to "fix" CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution. This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.

Efficient adsorption of chloroquine phosphate by a novel sodium alginate/tannic acid double-network hydrogel in a wide pH range.

In this work, a novel double-network composite hydrogel (SA/TA), composed of sodium alginate (SA) and tannic acid (TA), was designed and fabricated by a successive cross-linking method using Ti(IV) and Ca(II) as crosslinkers. SA/TA exhibited reinforced mechanical strength and anti-swelling properties because of the double-network structure. SA/TA was used as an adsorbent for removal of a popular antiviral drug, chloroquine phosphate (CQ), in water. The adsorption performance of SA/TA was systematically investigated, to study various effects including those of TA mass content, solution pH, adsorption time, and initial CQ concentration. Adsorption was also examined in presence of inorganic and organic coexisting substances commonly found in wastewater, and under different actual water samples. Batch experimental results indicated that SA/TA could maintain higher and more stable CQ uptakes within a wide solution pH range from 3.0 to 10.0, compared to its precursor, SA hydrogel, owing to the addition of TA-Ti(IV) coordination network. The maximum experimental CQ uptake exhibited by the 1:1 (by wt) SA/TA (SA/TA2) was as high as 0.699 mmol/g at the initial pH of 9.0. A high concentration of coexisting NaCl evidently reduced the CQ uptakes of SA/TA2 due to the electrostatic shielding effect, moreover, divalent cations including Ca(II) and Mg(II) also inhibited the adsorption of CQ due to competitive adsorption. However, humic acid had little effect on this adsorption. Considering the apparent adsorption performance, the aforementioned effects of various factors and the spectroscopic characterizations, multi-interactions are suggested for adsorption including chelation, electrostatic interactions, π-π electron donor-acceptor interaction and hydrogen bonding. SA/TA showed a slight loss in adsorption capacity toward CQ and sustained physicochemical structural stability, even after six adsorption-desorption cycles. In addition to CQ, SA/TA could be efficiently used for adsorption of two other antivirus drugs, namely, hydroxychloroquine sulfate and oseltamivir phosphate. This work provides an effective strategy for the design and fabrication of novel adsorbents that can effectively adsorb antiviral drugs over a wide pH range.

Carbon nanotube supported cobalt nickel sulphide nano-catalyst for degradation of chloroquine phosphate with peroxymonosulphate.

Carbon nanotubes supported cobalt nickel sulphide nanoparticles (nano-NiCo2S4@CNTs) were successfully prepared by a hydrothermal method as heterogeneous catalyst which can be used as an activator of peroxymonosulphate (PMS) for the degradation of chloroquine phosphate (CQP). Based on characterisation techniques, the prepared catalyst has excellent surface properties and structural stability. When different concentrations of CQP were treated with 0.2 g/L nano-NiCo2S4@CNTs and 1.0 mM PMS, the highest degradation rate could reach 99.86% after 30 min. Under the interference of pH, common anions and humic acid in the water environment, the reaction system can still achieve high degradation efficiency, showing excellent anti-interference ability and practical applicability. Furthermore, in the nano-NiCo2S4@CNTs/PMS system, according to the identification results of reactive oxygen species, the free radical and non-free radical pathway are responsible for the degradation of CQP, and the PMS mechanism activation was comprehensively proposed. Twelve intermediate products were detected in the degradation process, and the possible degradation pathways of CQP were proposed. This toxicity analysis demonstrates that the intermediate products formed during CQP degradation pose lower environmental risks compared to the original pollutant. In addition, after using the catalyst four cycles, the removal efficiency of CQP remains above 80%, indicating the excellent reusability and low metal ion leaching characteristics. Therefore, the nano-NiCo2S4@CNTs synthesised in this research has broad application prospects in activating PMS for wastewater treatment.

In Situ Generated Dye@MOF/COF Heterostructure for Fluorescence Detection of Chloroquine Phosphate and Folic Acid via Different Luminescent Channels.

Metal-organic framework (MOF) and covalent-organic framework (COF) hybrid materials can combine the unique properties of MOF and COF components, and their applications in fluorescence sensing have attracted more and more attention. Herein, ZIF-90 is grown on 3D-COF by a simple in situ growing method in which the 7-amino-4-methylcoumarin (AMC) is encapsulated in ZIF-90 to construct a fluorescent sensor. Chloroquine phosphate (CQP) can coordinate with Zn2+ to decompose the ZIF-90 and release AMC. At 365 nm excitation, the ratiometric fluorescence signal AMC/3D-COF (I430/I598) increases linearly with CQP in a linear range of 4 × 10-5 to 4 × 10-4 M in urine. Under 340 nm excitation, quantitative analysis of CQP in the serum (3 × 10-6 to 4 × 10-5 M) is based on the fluorescence intensity of Zn-CQP/3D-COF (I384/I598). In addition, AMC@ZIF-90/3D-COF (1) exhibits high anti-interference and selectivity in sensing of FA with a "turn off" mode, with a correlation range of 1 × 10-5 to 1 × 10-3 M. The fluorescence color changes triggered by CQP under different excitation conditions, and the different fluorescence responses caused by CQP make it a highly secure anticounterfeiting platform. The synthesized dye@MOF/COF hybrids not only provide a new way to integrate multiple emission to design fluorescent probes for differentiation detection but also offer ideas for the design of anticounterfeiting platforms.

PLM-101 is a novel and potent FLT3/RET inhibitor with less adverse effects in the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.

Mechanistic investigation of direct photodegradation of chloroquine phosphate under simulated sunlight.

Chloroquine phosphate (CQ) is an antiviral drug for Coronavirus Disease 2019 and an old drug for treatment of malaria, which has been detected in natural waters. Despite its prevalence, the environmental fate of CQ remains unclear. In this study, the direct photodegradation of CQ under simulated sunlight was investigated. The effect of various parameters such as pH, initial concentration and environmental matrix were examined. The photodegradation quantum yield of CQ (4.5 × 10-5-0.025) increased with the increasing pH value in the range of 6.0-10.0. The electron spin resonance (ESR) spectrometry and quenching experiments verified that the direct photodegradation of CQ was primarily associated with excited triplet states of CQ (3CQ*). The common ions had negligible effect and humic substances exhibited a negative effect on CQ photodegradation. The photoproducts were identified using high-resolution mass spectrometry and the photodegradation pathway of CQ was proposed. The direct photodegradation of CQ involved the cleavage of the C-Cl bond and substitution of the hydroxyl group, followed by further oxidation to yield carboxylic products. The photodegradation processes were further confirmed by the density functional theory (DFT) computation for the energy barrier of CQ dichlorination. The findings contribute to the assessment of the ecological risk associated with the overuse of Coronavirus drugs during global public health emergencies.

Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway.

Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients. In THP-1 and MV-4-11 cell lines, knockdown of autophagy-regulated genes ATG5 or MAP1LC3B significantly enhanced AML cell sensitivity to the chemotherapy drugs cytarabine, daunorubicin, and idarubicin. In silico screening, we found that chloroquine phosphate mimicked autophagy inactivation. We showed that chloroquine phosphate dose-dependently down-regulated the autophagy pathway in MV-4-11 cells. Furthermore, chloroquine phosphate exerted a synergistic antitumor effect with the chemotherapy drugs in vitro and in vivo. These results highlight autophagy activation as a drug resistance mechanism and the combination therapy of chloroquine phosphate and chemotherapy drugs can enhance anti-AML efficacy.

High-efficient degradation of chloroquine phosphate by oxygen doping MoS2 co-catalytic Fenton reaction.

To degrade the antiviral and antimalarial drug chloroquine phosphate (CQP), an oxygen doping MoS2 nanoflower (O-MoS2-230) co-catalyst was prepared by a hydrothermal method to construct an O-MoS2-230 co-catalytic Fenton system (O-MoS2-230/Fenton) without pH adjustment (initial pH 5.4). Remarkable CQP degradation efficiency (99.5 %) could be achieved in 10 min under suitable conditions ([co-catalyst] = 0.2 g L-1, [Fe2+]0 = 70 µM, [H2O2]0 = 0.4 mM) with a reaction rate constant of 0.24 min-1, which was 4.8 times that of MoS2 co-catalytic Fenton system (MoS2/Fenton). Compared to MoS2/Fenton, the system had 1.5 times more Fe2+ (28.4 µM) and showed a 24.0 % increase in H2O2 activation efficiency, reaching 50.0 %. The electron paramagnetic resonance (EPR) determinations and active species trapping experimental data revealed that •OH and 1O2 were responsible for CQP degradation. The combination of experiments and density functional theory (DFT) calculation demonstrates that O doping in MoS2 modifies the surface charge distribution, leading to an increase in its conductivity, thus accelerating the Fe3+/Fe2+ cycle and promoting reactive oxygen species (ROS) generation. Furthermore, O-MoS2-230/Fenton system exhibited excellent stability. This work reveals the degradation mechanism of accelerated Fe3+/Fe2+ cycle and abundant ROS in the O-MoS2-230/Fenton system and provides a promising technology for antibiotic pollutant degradation.

Toxicity Evaluation and Effect-Based Identification of Chlorine Disinfection Products of the Anti-COVID-19 Drug Chloroquine Phosphate.

Antiviral transformation products (TPs) generated during wastewater treatment are an environmental concern, as their discharge, in considerable amounts, into natural waters during a pandemic can pose possible risks to the aquatic environment. Identification of the hazardous TPs generated from antivirals during wastewater treatment is important. Herein, chloroquine phosphate (CQP), which was widely used during the coronavirus disease-19 (COVID-19) pandemic, was selected for research. We investigated the TPs generated from CQP during water chlorination. Zebrafish (Danio rerio) embryos were used to assess the developmental toxicity of CQP after water chlorination, and hazardous TPs were estimated using effect-directed analysis (EDA). Principal component analysis revealed that the developmental toxicity induced by chlorinated samples could be relevant to the formation of some halogenated TPs. Fractionation of the hazardous chlorinated sample, along with the bioassay and chemical analysis, identified halogenated TP387 as the main hazardous TP contributing to the developmental toxicity induced by chlorinated samples. TP387 could also be formed in real wastewater during chlorination in environmentally relevant conditions. This study provides a scientific basis for the further assessment of environmental risks of CQP after water chlorination and describes a method for identifying unknown hazardous TPs generated from pharmaceuticals during wastewater treatment.

Copper Nanoparticles and Reduced Graphene Oxide as an Electrode Modifier for the Development of an Electrochemical Sensing Platform for Chloroquine Phosphate Determination.

This study describes the use of copper nanoparticles (CuNPs) and reduced graphene oxide (rGO) as an electrode modifier for the determination of chloroquine phosphate (CQP). The synthetized rGO-CuNPs composite was morphologically characterized using scanning electron microscopy and electrochemically characterized using cyclic voltammetry. The parameters were optimized and the developed electrochemical sensor was applied in the determination of CQP using square-wave voltammetry (SWV). The analytical range for the determination of CQP was 0.5 to 110 µmol L-1 (one of the highest linear ranges for CQP considering electrochemical sensors), with limits of detection and quantification of 0.23 and 0.78 µmol L-1, respectively. Finally, the glassy carbon (GC) electrode modified with rGO-CuNPs was used for quantification of CQP in tap water; a study was carried out with interferents using SWV and obtained great results. The use of rGO-CuNP material as an electrode modifier was thus shown to be a good alternative for the development of low-cost devices for CQP analysis.

Treatment of condylomata acuminata caused by low-risk human papillomavirus with chloroquine phosphate gel.

Objective: To observe the stability and therapeutic effect of chloroquine phosphate gel on human condylomata acuminata (CA) caused by low-risk human papillomavirus (HPV). Methods: The appearance, viscosity, pH, chloroquine concentration, deethylchloroquine concentration and content uniformity of chloroquine phosphate gel were examined for 24 months, the gel met the quality standards throughout the 24-month observation. A nude mouse model harboring CA xenografts was used to observe the therapeutic effect of this gel on CA in vivo. Results: After 14 days of gel administration, compared with the control group, the treatment group had significantly smaller warts and significantly reduced DNA copy numbers of HPV6 and HPV11 in the wart tissues. Immunohistochemistry analysis of p53 protein expression in the wart tissues of the treatment group was significantly increased. Conclusion: Chloroquine phosphate gel was stable and effective against CA, possibly through the promotion of p53 protein expression to induce apoptosis, leading to the involution of warts.

Removal Performance and Mechanism of Emerging Pollutant Chloroquine Phosphate from Water by Iron and Magnesium Co-Modified Rape Straw Biochar.

Chloroquine phosphate (CQP) is effective in treating coronavirus disease 2019 (COVID-19); thus, its usage is rapidly increasing, which may pose a potential hazard to the environment and living organisms. However, there are limited findings on the removal of CQP in water. Herein, iron and magnesium co-modified rape straw biochar (Fe/Mg-RSB) was prepared to remove CQP from the aqueous solution. The results showed that Fe and Mg co-modification enhanced the adsorption efficiency of rape straw biochar (RSB) for CQP with the maximum adsorption capacity of 42.93 mg/g (at 308 K), which was about two times higher than that of RSB. The adsorption kinetics and isotherms analysis, as well as the physicochemical characterization analysis, demonstrated that the adsorption of CQP onto Fe/Mg-RSB was caused by the synergistic effect of pore filling, π-π interaction, hydrogen bonding, surface complexation, and electrostatic interaction. In addition, although solution pH and ionic strength affected the adsorption performance of CQP, Fe/Mg-RSB still had a high adsorption capability for CQP. Column adsorption experiments revealed that the Yoon-Nelson model better described the dynamic adsorption behavior of Fe/Mg-RSB. Furthermore, Fe/Mg-RSB had the potential for repeated use. Therefore, Fe and Mg co-modified biochar could be used for the remediation of CQP from contaminated water.

Electrochemical Determination of Chloroquine Phosphate in Real Samples Using a Diresorcinate-1,10-phenanthrolinecobalt(II)-Modified Glassy Carbon Electrode.

Chloroquine phosphate (CQP) is used for malaria treatment. As it is facing increasing resistance, it needs continuous monitoring using sensitive and specific detection methods. In this work, a voltammetric sensor was prepared by electropolymerization of a diresorcinate-1,10-phenanthrolinecobalt(II) complex on a glassy carbon electrode (poly(DHRPCo)/GCE) which was followingly characterized. Compared with a bare GCE, CQP showed single well shaped irreversible oxidative peak at the poly(DHRPCo)/GCE. The peak current showed excellent linearity with CQP concentration in the range of 0.005-300.0 µm with a detection limit of 0.39 nm. The response of CQP at poly(DHRPCo)/GCE was not influenced by the presence of amoxicillin, ciprofloxacillin and paracetamol in addition to its high stability and reproducibility. It was applied for detection of CQP in various real samples, including three brands of tablets, human blood serum, and urine samples. The detected amount in tablets were in the range 98.4-103.2 % of their labeled value. Spike recovery results in human blood serum, urine, and tablet samples were 99.35-100.28 %, 99.03-100.32 %, and 98.40-100.41 %, respectively. Interference recovery results with less than 4.60 % error, the lower limit of detection and the wider dynamic range than most of the previously reported methods validate the potential applicability of the proposed method for CQP determination in various real samples with complex matrices.

Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability - A Randomized Controlled Trial.

PURPOSE: To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability. METHODS: Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups: 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow-up was performed at postoperative 1, 3 and 6 months. RESULTS: At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). CONCLUSION: Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.

Insight into core -shell microporous zinc silicate adsorbent to eliminate antibiotics in aquatic environment under the COVID-19 pandemic.

Under the new crown pneumonia (COVID-19) epidemic, the intensive use of therapeutic drugs has caused certain hidden danger to the safety of the water environment. Therefore, the core-shell microporous zinc silicate (SiO2@ZSO) was successfully prepared and used for the adsorption of chloroquine phosphate (CQ), tetracycline (TC) and ciprofloxacin (CIP) for eliminating the threat of COVID-19. The adsorption efficiencies of 20 mg L-1 of CQ, TC and CIP by SiO2@ZSO were all up to 60% after 5 min. The adsorption capacity of SiO2@ZSO for CQ, TC and CIP can reach 49.01 mg g-1, 56.06 mg g-1 and 104.77 mg g-1, respectively. The adsorption process is primarily physical adsorption, which is heterogeneous, spontaneous and preferential. Moreover, the effects of temperature, pH, salinity, and reusability on the adsorption of CQ, TC, and CIP on SiO2@ZSO were investigated. The adsorption mechanism mainly involves electrostatic attraction, partitioning and hydrogen bonding, which is insightful through the changes of the elements and functional groups before and after adsorption. This work provides a solution to the problems faced by the treatment of pharmaceuticals wastewater under the COVID-19 epidemic.

Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters.

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel C-N bond linked conjugated microporous polymers (CMPs) (BPT-DMB-CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent C-N bond linked in the internal framework of BPT-DMB-CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich N-H bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g-1), BPT-DMB-CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g-1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT-DMB-CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π - π, C - H···π interactions and size-matching effect in the CQP adsorption system on BPT-DMB-CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT-DMB-CMP. BPT-DMB-CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

Role of trace TEMPO as electron shuttle in enhancing chloroquine phosphate elimination in UV-LED-driven persulfate activation process.

Chloroquine Phosphate (CP) is an antiviral drug used for treatment of COVID-19. It is released into wastewater and eventually contaminates natural water. This study reports an effective homogeneous catalysis way for CP degradation by the 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) enhanced persulfate (PDS) activation under UVB-LEDs irradiation at 305 nm. TEMPO at a low concentration (0.1 µM) enhanced CP degradation in UV305/PDS process in deionized water at different pHs, in different anions and different molecular weight dissolved organic matter solutions and in real surface water. The enhancement was verified to be attributed to the electron shuttle role of TEMPO, which promoted the yield of SO4 •- by enhancing electron donating capacity of the reacting system. The degradation products of CP and their acute toxicities suggested that UV305/PDS/TEMPO process has better performance on CP detoxification than UV305/PDS process. This study provides a new way to tackle the challenge of pharmaceutical pollutions in homogeneous photocatalysis process for natural water and sewage restoration.

[Degradation of Chloroquine Phosphate by UV-activated Persulfate].

The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO4-·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of CQP and major free radicals to explore its mechanism of influence. The results showed that the degradation efficiency of CQP could reach 91.3% after 10 min under UV/PS, which was significantly higher than that under UV, sunlight, or PS alone. At pH=6.9, the second-order rate reaction constants of CQP with HO· and SO4-· were 8.9×109 L·(mol·s)-1and 1.4×1010 L·(mol·s)-1, respectively, and the main active species was SO4-·. The degradation rate of CQP increased with increasing concentrations of PS and decreased with the addition of HCO3- and Cl-. The removal efficiency of CQP was inhibited under stronger alkaline conditions. N-de-ethylation, cleavage of the C-N bond, and hydrogen abstraction were proposed as the principal pathways of CQP degradation based on LC-MS analysis. The mineralization rate of CQP could be improved by increasing PS concentration and pH values. This study could be helpful for the treatment of anti-COVID-19 pharmaceutical wastewater.

Targeted Lipid Nanoparticles Encapsulating Dihydroartemisinin and Chloroquine Phosphate for Suppressing the Proliferation and Liver Metastasis of Colorectal Cancer.

Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro, attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo. Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.

Quadruple isotope dilution gas chromatography-mass spectrometry after simultaneous derivatization and spraying based fine droplet formation liquid phase microextraction method for the accurate and sensitive quantification of chloroquine phosphate in human serum, urine and saliva samples at trace levels.

This study presents an accurate and precise analytical strategy for the determination of chloroquine phosphate at trace levels in human body fluids (urine, serum, and saliva). Simultaneous derivatization-spraying based fine droplet formation-liquid phase microextraction (SD-SFDF-LPME) method was used to derivatize and preconcentrate the analyte prior to gas chromatography-mass spectrometry (GC-MS) measurements. Acetic anhydride was employed as derivatizing agent in this study. After optimizing the SD-SFDF-LPME method, the limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.16 and 0.53 mg/kg, respectively. Quadruple isotope dilution (ID4) was coupled to the SD-SFDF-LPME method in order to alleviate matrix effects and promote accuracy/precision of the method. Chloroquine acetamide-d3 was firstly synthesized in our research laboratory and used as the isotopic analogue of the analyte in the ID4 experiments. Superior percent recovery results (99.4% - 101.0%) with low standard deviation values were obtained for the spiked samples. This validated the developed SD-SFDF-LPME-ID4-GC-MS method as highly accurate and precise for the determination of chloroquine phosphate at trace levels. In addition, the isotopic analogue of the analyte was obtained via the acetamide derivative of the analyte, which is an alternative to obtain isotopic analogues of organic compounds that are not accessible or commercially available.