π-π+ Interaction Promoting the Absorption of Electroactive Chiral Selectors into the Cavity of Conductive Covalent Organic Framework for Enantioselective Sensing of Electrochemically Silent Molecules.

To date, achieving enantioselective electroanalysis for electrochemically silent chiral molecules is still highly desired. Here, an ionic covalent organic framework (COF) consisting of the pyridinium cation was derived from the tripyridinium Zincke salt and 1,4-phenylenediamine in a one-pot reaction. The electrochemical measurements revealed that the ionic backbone contributed to the electron transfer with a low charge transfer resistance. Besides, the π-π+ interaction between the pyridinium cation and ferrocenyl unit can promote the absorption of electroactive chiral ferrocenyl reagents into the hole of COF, so as to afford the electrochemical signals by themselves, replacing the testing enantiomers. As a result, the electroactive complex used as an electrochemical platform was highly effective at enantiomerically recognizing amino alcohols (prolinol, valinol, leucinol, and alaninol) and amino acids (methionine, serine, and penicillamine), giving the ratios of current intensity between l- and d-enantiomers in the range of 1.46-1.72. Moreover, the density functional theory calculations determined the possible intermolecular interactions between the testing enantiomers and chiral selector: namely, hydrogen bonds and electrostatic attractions. Overall, the present work offers an effective strategy to enlarge the electrochemical scope for chiral recognition based on electroactive chiral COFs.

Postsynthetic Modification Strategy for Constructing Electrochemiluminescence-Active Chiral Covalent Organic Frameworks Performing Efficient Enantioselective Sensing.

Electrochemiluminescence (ECL), integrating the characteristics of electrochemistry and fluorescence, has the advantages of high sensitivity and low background. However, only a few studies have been reported for enantioselective sensing based on the ECL-active platform because of the huge challenges in constructing tunable chiral ECL luminophores. Here, we developed a facile strategy to design and prepare ECL-active chiral covalent organic frameworks (COFs) Ph-triPy+-(R)-Ru(II) for enantioselective sensing. In such an artificial structure, the ionic skeleton of COFs was beneficial to the electron transfer on the working electrode surface and the chiral Ru-ligand was used as the chiral ECL-active luminophore. It was found that Ph-triPy+-(R)-Ru(II) coupled with sodium persulfate (Na2S2O8) as the coreactant exhibited obvious ECL signals. More importantly, a clear difference toward l- and d-enantiomers was observed in the response of the ECL intensity, resulting in a uniform recognition law. That is, for amino alcohols, d-enantiomers (1 mM) measured by Ph-triPy+-(R)-Ru(II) showed a higher ECL intensity compared with l-enantiomers. Differently, amino acids (1 mM) gave an inverse recognition phenomenon. The ECL intensity ratios between l- and d-enantiomers (1 mM) are in the range of 1.25-1.94 for serine, aspartic acid, glutamic acid, valine, leucine, leucinol, and valinol. What is more interesting is that the ECL intensity was closely related to the concentration of l-amino alcohols and d-amino acids, whereas their inverse configurations remained unchanged. In a word, the present concept demonstrates a feasible direction toward chiral ECL-active COFs and their potential for efficient enantioselective sensing.

A Liquid-Liquid Interfacial Strategy for Construction of Electroactive Chiral Covalent-Organic Frameworks with the Aim to Enlarge the Testing Scope of Chiral Electroanalysis.

Although electroactive chiral covalent-organic frameworks (CCOFs) are considered an ideal platform for chiral electroanalysis, they are rarely reported due to the difficult selection of suitable precursors. Here, a facile strategy of liquid-liquid interfacial polymerization was carried out to synthesize the target electroactive CCOFs Ph-Py+-(S,S)-DPEA·PF6- and Ph-Py+-(R,R)-DPEA·PF6-. That is, a trivalent Zincke salt (4,4',4″-(benzene-1,3,5-triyl)tris(1-(2,4-dinitrophenyl)pyridin-1-ium)) trichloride (Ph-Py+-NO2) and enantiopure 1,2-diphenylethylenediamine (DPEA) were dissolved in water and chloroform, respectively. The Zincke reaction occurs at the interface, resulting in uniform porosity. As expected, the cyclic voltammetry and differential pulse voltammetry measurements showed that the tripyridinium units of the CCOFs afforded obvious electrochemical responses. When Ph-Py+-(S,S)-DPEA·PF6- was modified onto the surface of a glassy carbon electrode as a chiral sensor, the molecules, which included tryptophan, aspartic acid, serine, tyrosine, glutamic acid, mandelic acid, and malic acid, were enantioselectively recognized in the response of the peak current. Very importantly, the discriminative electrochemical signals were derived from Ph-Py+-(S,S)-DPEA·PF6-. The best peak current ratios between l- and d-enantiomers were in the range of 1.31-2.68. Besides, a good linear relationship between peak currents and enantiomeric excess (ee) values was established, which was successfully harnessed to determine the ee values for unknown samples. In a word, the current work provides new insight and potential of electroactive CCOFs for enantioselective sensing in a broad range.

Multi-omics analysis to identify susceptibility genes for colorectal cancer.

Most genetic variants for colorectal cancer (CRC) identified in genome-wide association studies (GWAS) are located in intergenic regions, implying pathogenic dysregulations of gene expression. However, comprehensive assessments of target genes in CRC remain to be explored. We conducted a multi-omics analysis using transcriptome and/or DNA methylation data from the Genotype-Tissue Expression, The Cancer Genome Atlas and the Colonomics projects. We identified 116 putative target genes for 45 GWAS-identified variants. Using summary-data-based Mendelian randomization approach (SMR), we demonstrated that the CRC susceptibility for 29 out of the 45 CRC variants may be mediated by cis-effects on gene regulation. At a cutoff of the Bonferroni-corrected PSMR < 0.05, we determined 66 putative susceptibility genes, including 39 genes that have not been previously reported. We further performed in vitro assays for two selected genes, DIP2B and SFMBT1, and provide functional evidence that they play a vital role in colorectal carcinogenesis via disrupting cell behavior, including migration, invasion and epithelial-mesenchymal transition. Our study reveals a large number of putative novel susceptibility genes and provides additional insight into the underlying mechanisms for CRC genetic risk loci.

Recent advances of optically active helical polymers as adsorbents and chiral stationary phases for chiral resolution.

Chiral resolution is very important and still a big challenge due to different biological activity and same physicochemical property of one pair (R)- and (S)-isomer. There is no doubt that chiral selectors are essentially needed for chiral resolution, which can stereoselectively interact with a pair of isomers. To date, a large amount of optically active helical polymers as chiral selectors have been synthesized via two strategies. First, the target helical polymers are derived from natural polysaccharide such as cellulose and amylose. Second, they can be synthesized by polymerization of chiral monomers. Alternatively, an achiral polymer is prepared first followed by static or dynamic chiral induction. Furthermore, a part of them is harnessed as chiral stationary phases for chromatographic chiral separation and as chiral adsorbents for enantioselective adsorption/crystallization, resulting in good enantioseparation efficiency. In summary, the present review will focus on recent progress of the polymers with optical activity for chiral resolution, especially the literature published in the past 10 years. In addition, development prospects and future challenges of optically active helical polymers will be discussed in detail.

Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis.

BACKGROUND: Pharmacological modulation of cannabinoid 2 receptor (CB2R) is a promising therapeutic strategy for pulmonary fibrosis (PF). Thus, to develop CB2R selective ligands with new chemical space has attracted much research interests. This work aims to discover a novel CB2R agonist from an in-house library, and to evaluate its therapeutic effects on PF model, as well as to disclose the pharmacological mechanism. METHODS: Virtual screening was used to identify the candidate ligand for CB2R from a newly established in-house library. Both in vivo experiments on PF rat model and in vitro experiments on cells were performed to investigate the therapeutic effects of the lead compound and underlying mechanism. RESULTS: A "natural product-like" pyrano[2,3-b]pyridine derivative, YX-2102 was identified that bound to CB2R with high affinity. Intraperitoneal YX-2102 injections significantly ameliorated lung injury, inflammation and fibrosis in a rat model of PF induced by bleomycin (BLM). On one hand, YX-2102 inhibited inflammatory response at least partially through modulating macrophages polarization thereby exerting protective effects. Whereas, on the other hand, YX-2102 significantly upregulated CB2R expression in alveolar epithelial cells in vivo. Its pretreatment inhibited lung alveolar epithelial-to-mesenchymal transition (EMT) in vitro and PF model induced by transforming growth factor beta-1 (TGF-ß1) via a CB2 receptor-dependent pathway. Further studies suggested that the Nrf2-Smad7 pathway might be involved in. CONCLUSION: These findings suggest that CB2R is a potential target for PF treatment and YX-2102 is a promising CB2R agonist with new chemical space.

Chiral Ru-Based Covalent Organic Frameworks as An Electrochemiluminescence-Active Platform for the Enantioselective Sensing of Amino Acids.

Although several studies related with the electrochemiluminescence (ECL) technique have been reported for chiral discrimination, it still has to face some limitations, namely, complex synthetic pathways and a relatively low recognition efficiency. Herein, this study introduces a facile strategy for the synthesis of ECL-active chiral covalent organic frameworks (COFs) employed as a chiral recognition platform. In this artificial structure, ruthenium(II) coordinated with the dipyridyl unit of the COF and enantiopure cyclohexane-1,2-diamine was harnessed as the ECL-active unit, which gave strong ECL emission in the presence of the coreactant reagent (K2S2O8). When the as-prepared COF was used as a chiral ECL-active platform, clear discrimination was observed in the response of the ECL intensity toward l- and d-enantiomers of amino acids, including tryptophan, leucine, methionine, threonine, and histidine. The biggest ratio of the ECL intensity between different configurations was up to 1.75. More importantly, a good linear relationship between the enantiomeric composition and the ECL intensity was established, which was successfully employed to determine the unknown enantiomeric compositions of the real samples. In brief, we believe that the proposed ECL-based chiral platform provides an important reference for the determination of the configuration and enantiomeric compositions.

Comparison of Two Representative Methods for Differentiation of Human Induced Pluripotent Stem Cells into Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are adult pluripotent stem cells which have been widely used in regenerative medicine. As somatic tissue-derived MSCs are restricted by limited donation, quality variations, and biosafety, the past 10 years have seen a great rise in efforts to generate MSCs from human induced pluripotent stem cells (hiPSCs). Past and recent efforts in the differentiation of hiPSCs into MSCs have been centered around two culture methodologies: (1) the formation of embryoid bodies (EBs) and (2) the use of monolayer culture. This protocol describes these two representative methods in deriving MSC from hiPSCs. Each method presents its advantages and disadvantages, including time, cost, cell proliferation ability, the expression of MSC markers, and their capability of differentiation in vitro. This protocol demonstrates that both methods can derive mature and functional MSCs from hiPSCs. The monolayer method is characterized by lower cost, simpler operation, and easier osteogenic differentiation, while the EB method is characterized by lower time consumption.

TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy.

Background: Cisplatin is a widely used anti-tumor agent but its use is frequently limited by nephrotoxicity. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel which is generally viewed as a sensor of oxidative stress, and increasing evidence supports its link with autophagy, a critical process for organelle homeostasis. Methods: Cisplatin-induced cell injury and mitochondrial damage were both assessed in WT and Trpm2-knockout mice and primary cells. RNA sequencing, immunofluorescence staining, immunoblotting and flowcytometry were applied to interpret the mechanism of TRPM2 in cisplatin nephrotoxicity. Results: Knockout of TRPM2 exacerbates renal dysfunction, tubular injury and cell apoptosis in a model of acute kidney injury (AKI) induced by treatment with cisplatin. Cisplatin-caused tubular mitochondrial damage is aggravated in TRPM2-deficient mice and cells and, conversely, alleviated by treatment with Mito-TEMPO, a mitochondrial ROS scavenger. TRPM2 deficiency hinders cisplatin-induced autophagy via blockage of Ca2+ influx and subsequent up-regulation of AKT-mTOR signaling. Consistently, cisplatin-induced tubular mitochondrial damage, cell apoptosis and renal dysfunction in TRPM2-deficient mice are mitigated by treatment with a mTOR inhibitor. Conclusion: Our results suggest that the TRPM2 channel plays a protective role in cisplatin-induced AKI via modulating the Ca2+-AKT-mTOR signaling pathway and autophagy, providing novel insights into the pathogenesis of kidney injury.

A protocol for the generation of patient-specific iPSC lines from peripheral blood mononuclear cells.

The current procedure thoroughly explains how to reprogram induced pluripotent stem cells (iPSCs) from the patient's peripheral blood mononuclear cells (PBMCs), a less invasive source; e.g., somatic cells. We describe how to isolate PBMCs and reprogram them into iPSCs by electroporation. Furthermore, we provide an alternative approach to generating iPSC using Geltrex or Matrigel matrix to replace MEF-feeder. The challenge of this process is the relatively lower cell survival rates of PBMCs due to the damage of electroporation. For complete details on the use and execution of this protocol, please refer to Hu et al. (2021).

A Real-Time Strategy for Chiroptical Sensing and Enantiomeric Excess Determination of Primary Amines via an Acid-Base Reaction.

Two achiral aromatic carboxylic acids that included the 1,8-naphthalimide group and an imidazolium cation were synthesized and exploited as chiroptical sensors. These compounds showed the real-time discrimination and enantiomeric excess determination of chiral amines and amino alcohols via an acid-base interaction, especially for UV-silent chiral compounds.

An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury.

Acute kidney injury (AKI) is common in hospital patients. Delayed diagnosis and treatment of AKI due to the lack of efficient early diagnosis is an important cause of its high mortality. While fluorescence imaging seems promising to non-intrusively interrogate AKI-related biomarkers, the low kidney contrast of many fluorophores conferred by their relatively low abundance of distribution in the kidney limits their application for AKI detection. Herein, we discovered a near-infrared fluorophore with inherent kidney-targeting ability. Based on this fluorophore, a fluorogenic probe (KNP-1) was developed by targeting peroxynitrite (ONOO-), which is upregulated at the early onset of AKI. KNP-1 exhibits desirable kidney distribution after intravenous administration and is fluorescent only after activation by ONOO-. These properties lead to excellent kidney contrast imaging results. KNP-1 is capable of detecting both nephrotoxin-induced and ischemia-reperfusion injury-induced AKI in live mice. Temporally resolved imaging of AKI-disease model mice with KNP-1 suggests a gradual increase in renal ONOO- levels with disease progression. Notably, the upregulation of ONOO- can be observed at least 24 h earlier than the clinically popular sCr and BUN methods. Blocking ONOO- generation also proves beneficial. These results highlight the applicability of this inherently tissue targeting-based strategy for designing probes with desirable imaging contrast; potentiate ONOO- as a biomarker and target for AKI early diagnosis and medical intervention; and imply the clinical relevance of KNP-1 for AKI early detection.

Gastric environment-stable oral nanocarriers for in situ colorectal cancer therapy.

Colorectal cancer (CRC) is a prevalent and fatal cancer. Oral administration provided the potential for in situ treatment of the colorectal cancer. However, drugs couldn't be well-absorbed mainly due to its degradation in the gastric area and poor intestinal permeability. In this study, we synthesized deoxycholic acid and hydroxybutyl decorated chitosan nanoparticles (DAHBC NPs) as oral curcumin (CUR) delivery system for colorectal cancer treatment. DAHBC with lower critical solution temperature (LCST) below 37 °C (27-33 °C) was obtained. DAHBC NPs were correspondingly stable in simulated gastric conditions (pH 1.2, 37 °C), due to the offset of size change between pH-responsive expansion and thermo-responsive shrinkage. In simulated intestinal tract (pH 7.0-7.4, 37 °C), DAHBC NPs exhibited burst release of CUR owing to the onefold effect of thermo-responsive shrinkage. DAHBC27 NPs showed the minimum CUR leakage (~10%) in simulated gastric conditions, because a furthest temperature-sensitive shrinkage caused by the lowest LCST offset the expansion in acid environment. DAHBC27 NPs induced ~10-fold increased (P < 0.05) CUR absorption by paracellular transport pathway, compared to the free CUR. Thus, DAHBC NPs stabilized in the gastric environment may be a promising oral drugs delivery system for effective in situ colorectal cancer therapy.

Author Correction: Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Herb Formula ZhenRongDan Balances Sex Hormones, Modulates Organ Atrophy, and Restores ERα and ERß Expressions in Ovariectomized Rats.

Herb mixtures are widely used for treatment of the menopausal syndrome long before the hormonal therapy. However, there is insufficient data for herb remedies in treating menopausal syndromes. Here we aim to investigate the effect of ZhenRongDan (ZRD) in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing organ atrophy in menopausal rats. Rats that underwent bilateral ovariectomy were used in the experiments; the effects of ZRD on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol (E2) levels were observed. Histology of vagina and ERs expression in vagina, uterus, and adrenal gland were also examined. ELISAs were used to analyze the changes of FSH, LH, PRL, and E2 in serum, and the morphological changes of the cervical epithelium cells were observed by Hematoxylin & Eosin (H&E) staining. Immunohistochemistry and western blot were applied to detect estrogen receptors subtypes alpha (ERα) and beta (ERß) expression in vagina, uterus, and adrenal gland. We found that ZRD could significantly reduce the weight of the adrenal gland and increase the weight of the uterus. It could decrease the release of FSH and LH as well as increasing E2 and PRL levels. Furthermore, ZRD could improve the number of cervical vaginal epithelial cells and increase the thickness of the vaginal wall. And the altered expressions of ERα and ERß are also restored by ZRD. ZRD could obviously relieve the endocrine disorders, modulate organ atrophy, and restore ERα and ERß expression in the ovariectomized rat model.

Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction.

Radiation-induced lung fibrosis (RILF) is a long-term adverse effect of curative radiotherapy. The accumulation of myofibroblasts in fibroblastic foci is a pivotal feature of RILF. In the study, we found the inhibitory effect of grape seed proanthocyanidins (GSPs) on irradiation-induced differentiation of human fetal lung fibroblasts (HFL1). To explore the mechanism by which GSPs inhibit fibroblast differentiation, we measured the reactive oxygen species (ROS) levels, mitochondrial function, mitochondrial dynamics, glycolysis and the signaling molecules involved in fibroblast transdifferentiation. GSPs significantly reduced the production of cellular and mitochondrial ROS after radiation. The increases in mitochondrial respiration, proton leak, mitochondrial ATP production, lactate release and glucose consumption that occurred in response to irradiation were ameliorated by GSPs. Furthermore, GSPs increased the activity of complex I and improved the mitochondrial dynamics, which were disturbed by irradiation. In addition, the elevation of phosphorylation of p38MAPK and Akt, and Nox4 expression induced by irradiation were attenuated by GSPs. Blocking Nox4 attenuated irradiation-mediated fibroblast differentiation. Taken together, these results indicate that GSPs have the ability to inhibit irradiation-induced fibroblast-to-myofibroblast differentiation by ameliorating mitochondrial dynamics and mitochondrial complex I activity, regulating mitochondrial ROS production, ATP production, lactate release, glucose consumption and thereby inhibiting p38MAPK-Akt-Nox4 pathway.

Moving and unsinkable graphene sheets immobilized enzyme for microfluidic biocatalysis.

Enzymatic catalysis in microreactors has attracted growing scientific interest because of high specific surface enabling heat and mass transfer and easier control of reaction parameters in microreactors. However, two major challenges that limit their application are fast inactivation and the inability to the biocatalysts in microchannel reactors. A fluid and unsinkable immobilized enzyme were firstly applied in a microchannel reactor for biocatalysis in this study. Functionalized forms of graphene-immobilized naringinase flowing in microchannels have yielded excellent results for isoquercitrin production. A maximum yield of 92.24 ± 3.26% was obtained after 20 min in a microchannel reactor. Ten cycles of enzymatic hydrolysis reaction were successively completed and an enzyme activity above 85.51 ± 2.76% was maintained. The kinetic parameter V m/K m increased to 1.9-fold and reaction time was decreased to 1/3 compared with that in a batch reactor. These results indicated that the moving and unsinkable graphene sheets immobilized enzyme with a high persistent specificity and a mild catalytic characteristic enabled the repetitive use of enzyme and significant cost saving for the application of enzyme catalysis. Thus, the developed method has provided an efficient and simple approach for the productive and repeatable microfluidic biocatalysis.

Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery.

Here we described nano-polyplexes (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) as novel potential carriers for oral gene vaccines delivery. Aerolysin gene (aerA) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-HA/aerA (OHA) NPs. OHA NPs performed the optimal parameters, i.e. smallest (154.5±9.4nm), positive charged (+7.9±0.5mV) and monodispersed system with the N/P ratio of 5 and OCMCS/HA weight ratio of 4. Upon the introduction of HA, OHA NPs was beneficial for the DNA release in intestinal environments in comparison to OA NPs. The mean fluorescence intensity detected in Caco-2 cells incubated with OHA NPs was about 2.5-fold higher than that of OA NPs; however, it decreased significantly in the presence of excess free HA. The OHA NPs and OA NPs decreased the transepithelial electric resistance (TEER) of Caco-2 monolayers obviously and induced increasing the apparent permeability coefficient (Papp) of DNA by 5.45-6.09 folds compared with free DNA. Significantly higher (P<0.05) antigen-specific antibodies were detected in serum after orally immunized with OHA NPs than that immunized with OA NPs and DNA alone in carps. These results enable the OHA NPs might resolve challenges arising from gastrointestinal damage to gene antigens, and offer an approach applicable for oral vaccination.

Influence of the graft density of hydrophobic groups on thermo-responsive nanoparticles for anti-cancer drugs delivery.

A series of deoxycholate-chitosan-hydroxybutyl (DAHBCs) with different degrees of substitution (DS) of hydrophobic deoxycholate (DOCA) were successfully synthesized. The lower critical solution temperature (LCST) of various DAHBCs could be adjusted from 35.4°C to 42.1°C by controlling the graft density of DOCA. DAHBCs could self-assemble into nanoparticles (NPs) which gradually evolved from irregular aggregates to spherical particles with the decrease of the DS of DOCA groups. The size of DAHBCs NPs ranged from 100nm to 250nm and their zeta potential varied between 3.85 and 12.37mV. Hemolysis tests and protein adsorption assay exhibited DAHBCs NPs had few adverse effects on the blood components even at a concentration as high as 1mg/mL. DAHBCs NPs showed high curcumin (CUR) encapsulation efficiency up to 80%. CUR-loaded DAHBCs NPs displayed thermal-dependent drug release profiles, and the release rate of CUR (∼75%) was significantly (p<0.05) accelerated at a temperature above the LCST compared with that (∼40%) below the LCST. Cytotoxicity analysis identified no toxicity associated with DAHBCs NPs at a concentration up to 0.5mg/mL. However, when the cells were incubated with the CUR-loaded NPs, their growth was significantly inhibited at 43°C (>LCST), demonstrating the thermal-responsive release of encapsulated cargoes from the NPs. With the capacity to control the LCST of DAHBCs NPs at specific temperatures, it could be speculated that DAHBCs NPs might serve as a promising thermo-responsive nanoplatform for the delivery of antitumor drugs.