Precise modulation and use of reactive oxygen species for immunotherapy.

Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.

Role of Zhiqiao Chuanlian decoction in the treatment of food accumulation fever: Network pharmacology and animal experiments.

Objective: Food accumulation fever (FAF), a common clinical disease in children, is generally induced by the excessive intake of high-calorie or high-fat foods. Zhiqiao Chuanlian decoction (ZQCLD) is a classical traditional Chinese medicine (TCM) that may have therapeutic effects on FAF. Methods: Network pharmacological analyses of ZQCLD and FAF were conducted. Animal experiments lasted for 14 days. Rats in the model, positive control, and low-, medium-, and high-dose groups were fed a high-calorie diet. On days 11-14, the positive group was given a domperidone solution. The low-, medium-, and high-dose groups were administered different concentrations of ZQCLD. The body temperature, gastric emptying rate, and intestinal propulsion rate were measured. Relevant indicators were determined by ELISA. Results: The main target proteins included IL-1ß, C-C motif chemokine 2 (CCL2), prostaglandin G/H synthase 2 (PTGS2), transcription factor AP-1 (JUN), haem oxygenase 1 (HMOX1), interferon-gamma (IFN-γ), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and inducible nitric oxide synthase (NOS2/iNOS). Compared with those in the control group, body weight, gastric emptying rate, intestinal propulsion rate, and neuronal nitric oxide synthase (NOS1/nNOS) levels were significantly lower in the model group, whereas body temperature and endotoxin, interleukin-1ß (IL-1ß), PGE2, and iNOS levels were increased. In each treatment group, body temperature and PGE2 levels returned to normal levels. Compared with those in the model group, the gastric emptying rates in the positive group and the low- and medium-dose groups increased; the intestinal propulsion rates were higher in the medium- and high-dose groups, whereas the endotoxin and IL-1ß levels were lower; and the nNOS level was higher in the high-dose group, whereas the iNOS level was lower. Conclusions: ZQCLD may treat FAF by regulating jejunal IL-1ß and nNOS, serum endotoxin, and hypothalamic PGE2 and iNOS levels.

Dietary rutin alleviated the damage by cold stress on inflammation reaction, tight junction protein and intestinal microbial flora in the mice intestine.

Low temperature is a common stress source for the poultry industry in the north of China. However, the low energy consuming and economical way to reduce the negative effects from cold stress is still limited. Therefore, the aim of this study was to investigate the effect of rutin on intestinal barrier in mice under low temperature. The cold stress model was established at 4°C for 3 h each day and the experiment lasted for 21 days. Forty Balb/c mice were randomly divided into four treatments: CON, normal temperature with the basal diet; RUT, normal temperature with the basal diet +150 mg/kg body weight (BW) of rutin; CS, mice under cold stress with basal diet; CR, 150 mg/kg of BW rutin under cold stress. Rutin supplementation significantly increased the ileum villus-to-crypt ratio compared with these non-supplemented treatments. Rutin attenuated the hypothermia induced morphological damage in the ileum. In addition, rutin improved the antioxidant capacity of mice under cold stress. Rutin supplementation significantly increased the trypsin activity and inhibited the lipase in cold stressed mice. Rutin supplementation significantly inhibited the production of inflammatory factors induced by cold stress. Rutin induced the inhibition of TLR4 and NF-кB, thereby reducing the expression of inflammation-related genes. In addition, rutin improved the reduction of the intestinal claudin-1 and occludin expression in those mice in the cold stress (P < .05) and improved the intestinal ZO-1 expression in cold stressed mice. Finally, rutin alleviated the dysregulation of intestinal microflora in the mice under cold stress.

Design, Fabrication, and Characterization of Inkjet-Printed Organic Piezoresistive Tactile Sensor on Flexible Substrate.

In this paper, we propose a novel tactile sensor with a "fingerprint" design, named due to its spiral shape and dimensions of 3.80 mm × 3.80 mm. The sensor is duplicated in a four-by-four array containing 16 tactile sensors to form a "SkinCell" pad of approximately 45 mm by 29 mm. The SkinCell was fabricated using a custom-built microfabrication platform called the NeXus which contains additive deposition tools and several robotic systems. We used the NeXus' six-degrees-of-freedom robotic platform with two different inkjet printers to deposit a conductive silver ink sensor electrode as well as the organic piezoresistive polymer PEDOT:PSS-Poly (3,4-ethylene dioxythiophene)-poly(styrene sulfonate) of our tactile sensor. Printing deposition profiles of 100-micron- and 250-micron-thick layers were measured using microscopy. The resulting structure was sintered in an oven and laminated. The lamination consisted of two different sensor sheets placed back-to-back to create a half-Wheatstone-bridge configuration, doubling the sensitivity and accomplishing temperature compensation. The resulting sensor array was then sandwiched between two layers of silicone elastomer that had protrusions and inner cavities to concentrate stresses and strains and increase the detection resolution. Furthermore, the tactile sensor was characterized under static and dynamic force loading. Over 180,000 cycles of indentation were conducted to establish its durability and repeatability. The results demonstrate that the SkinCell has an average spatial resolution of 0.827 mm, an average sensitivity of 0.328 mΩ/Ω/N, expressed as the change in resistance per force in Newtons, an average sensitivity of 1.795 µV/N at a loading pressure of 2.365 PSI, and a dynamic response time constant of 63 ms which make it suitable for both large area skins and fingertip human-robot interaction applications.

Research and evaluation on students' emotional attachment to campus landscape renewal coupling emotional attachment scale and public sentiment analysis: a case study of the "Heart of Forest" in Beijing Forestry University.

In the era of stock renewal, the construction of university campuses in China's first-tier cities has shifted from demolition and construction to renewal and upgrading, in which public landscape space is the main environment for students' daily life, learning and entertainment. Especially during the outbreak of the recent COVID-19 epidemic, it has become an important way for students to interact with nature and obtain emotional healing. In the existing studies, there is a lack of discussion on the correlation between the spatial characteristics of the updated campus landscape and students' emotional attachment, and there are few quantitative studies. Based on this, this paper takes the "Heart of Forest" landscape space as an example, and integrates multi-dimensional quantitative methods including emotional attachment scale and public semantic analysis to study and evaluate the characteristics of landscape space that affect students' emotional attachment. The results show that: (1) Overall, the landscape space renewal of the Heart of Forest provides students with positive emotional experiences and effectively enhances students' emotional attachment as well as sense of belonging to the campus. (2) Among them, the material characteristics of the site including nature-related elements, materials, structures play a positive role in promoting the vast majority of students in the process of establishing emotional attachment, which is particularly obvious for students majoring in landscape, architecture and urban planning. (3) Whether the public social space can effectively provide students with a good emotional experience is closely related to the frequency and purpose of students' use of the space. (4) The interactive characteristics such as changeability and playability fail to promote emotional attachment because of lacking of management and maintenance. The renewal and transformation of the "Heart of Forest" landscape space is generally successful in promoting students' emotional attachment, and provides a reference for the future campus landscape renewal design from different angles. In addition, the quantitative study of emotional attachment constructed in this paper coupled with multi-dimensional data provides a method for the evaluation of students' emotional experience of campus landscape.

Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity.

DNA derived from chemotherapeutics-killed tumor cells is one of the most important damage-associated molecular patterns that can activate the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway in antigen-presenting cells (APCs) and promote antitumor immunity. However, conventional chemotherapy displays limited tumor cell killing and ineffective transfer of stable tumor DNA to APCs. Here we show that liposomes loaded with an optimized ratio of indocyanine green and doxorubicin, denoted as LID, efficiently generate reactive oxygen species upon exposure to ultrasound. LID plus ultrasound enhance the nuclear delivery of doxorubicin, induce tumor mitochondrial DNA oxidation, and promote oxidized tumor mitochondrial DNA transfer to APCs for effective activation of cGAS-STING signaling. Depleting tumor mitochondrial DNA or knocking out STING in APCs compromises the activation of APCs. Furthermore, systemic injection of LID plus ultrasound over the tumor lead to targeted cytotoxicity and STING activation, eliciting potent antitumor T cell immunity, which upon the combination with immune checkpoint blockade leads to regression of bilateral MC38, CT26, and orthotopic 4T1 tumors in female mice. Our study sheds light on the importance of oxidized tumor mitochondrial DNA in STING-mediated antitumor immunity and may inspire the development of more effective strategies for cancer immunotherapy.

Oxidative stability and gelation properties of myofibrillar protein from chicken breast after post-mortem frozen storage as influenced by phenolic compound-pterostilbene.

The aim of this study was to elucidate the effects of dietary pterostilbene supplementation on physicochemical changes and gel properties of myofibrillar protein (MP) in chicken when subjected to short-term frozen storage. The results showed that pterostilbene supplementation diminished the oxidation of MP compared to the control, as the carbonyl content was significantly reduced and the loss of sulfhydryl and free amino groups was slowed. Meanwhile, the surface hydrophobicity and insolubility of MP were significantly reduced. FT-IR and endogenous fluorescence spectroscopy analysis indicated that dietary pterostilbene inhibited the unfolding of protein structure and the transition of α-helix to ß-sheet structure. The integrity of the protein structure contributed to the gel quality. The strength, whiteness and water-holding capacity (WHC) of MP gels were improved in the pterostilbene treatment group. In terms of microstructure, pterostilbene facilitated the formation of dense and homogeneous gel network structure. In summary, these findings suggest that pterostilbene could be used as a dietary supplement to maintain the structural stability of MP in postmortem chicken breast muscle, allowing for excellent gel functional properties.

Optimization of fermentation conditions, purification and rheological properties of poly (γ-glutamic acid) produced by Bacillus subtilis 1006-3.

This study aimed to investigate the optimal fermentation condition, purification and rheological properties of extracellular polymers produced by Bacillus subtilis 1006-3. An optimum temperature of 30.2 °C, inoculation amount of 6.1%, and pH of 8.2 were determined via Response Surface Methodology. The result of amino acid analysis and gel electrophoresis indicated that the obtained polymer contained only glutamic acid, with a wide molecular weight range. This polymer was finally determined as γ-PGA by infrared spectroscopy. The γ-PGA solution displayed a behavior of pseudoplastic non-Newtonian fluid with shear thinning properties, which can be described by the Ostward-de Waele power law model. The apparent viscosity of γ-PGA solution increased with the increase in its concentration from 1% to 10%. The deviation in pH from neutral value, and the addition of NaCl or MgCl2 can reduce the apparent viscosity of γ-PGA solution, and it was more sensitive to Mg2+ than to Na+ addition. At the concentration of 4, 6, and 8%, γ-PGA solution showed predominantly viscous response in the range of 0.1-100 rad/s angular frequency (G″>G'). These results indicated the potential application of the γ-PGA as a thickening agent.

Characterization of Structural and Physicochemical Properties of an Exopolysaccharide Produced by Enterococcus sp. F2 From Fermented Soya Beans.

The present study sought to isolate a novel exopolysaccharide (EPS-F2) from Enterococcus sp. F2 through ethanol precipitation, anion-exchange, and gel-filtration chromatography and characterize the physicochemical properties by spectral techniques. EPS-F2 was identified as a neutral homo-exopolysaccharide composed of only glucose with a high molecular weight of 1.108 × 108 g/mol. It contained →6)-α-D-Glcp-(1→ linkage in the main chain and →3, 6)-α-D-Glcp-(1→ branch chain). Moreover, EPS-F2 possessed excellent thermal stability (266.6°C), water holding capacity (882.5%), oil holding capacity (1867.76%), and emulsifying activity against various edible oils. The steady shear experiments exhibited stable pseudo plasticity under various conditions (concentrations, temperatures, and pHs). The dynamic oscillatory measurements revealed that EPS-F2 showed a liquid-like behavior at a low concentration (2.5%), while a solid-like behavior at high concentrations (3.0 and 3.5%). Overall, these results suggest that EPS-F2 could be a potential alternative source of functional additives and ingredients and be applied in food industries.

An Improved Chinese String Comparator for Bloom Filter Based Privacy-Preserving Record Linkage.

With the development of information technology, it has become a popular topic to share data from multiple sources without privacy disclosure problems. Privacy-preserving record linkage (PPRL) can link the data that truly matches and does not disclose personal information. In the existing studies, the techniques of PPRL have mostly been studied based on the alphabetic language, which is much different from the Chinese language environment. In this paper, Chinese characters (identification fields in record pairs) are encoded into strings composed of letters and numbers by using the SoundShape code according to their shapes and pronunciations. Then, the SoundShape codes are encrypted by Bloom filter, and the similarity of encrypted fields is calculated by Dice similarity. In this method, the false positive rate of Bloom filter and different proportions of sound code and shape code are considered. Finally, we performed the above methods on the synthetic datasets, and compared the precision, recall, F1-score and computational time with different values of false positive rate and proportion. The results showed that our method for PPRL in Chinese language environment improved the quality of the classification results and outperformed others with a relatively low additional cost of computation.

Mechanism of Cr(VI) reduction by Lysinibacillus sp. HST-98, a newly isolated Cr (VI)-reducing strain.

Facing the increasingly severe Cr(VI) pollution, bioreduction has proved to be an eco-friendly remediation method. An isolated strain identified as Lysinibacillus can relatively reduce Cr(VI) well. Even if the concentration of Cr(VI) increased to 250mg/L, the strain HST-98 could also grow and remove Cr(VI) well. After optimization of reaction conditions, the optimal pH, temperature, and electron donor are 8~9, 36°C, and sodium lactate, respectively. Coexisting metal ions such as Cu2+, Co2+, and Mn2+ are beneficial to reduce Cr(VI), while Zn2+, Ni2+, and Cd2+ are just the opposite. What is more, the mechanism of the reduction by the strain HST-98 is chiefly mediated by intracellular enzymes. After gene sequence homology blast and analysis, the genes and enzymes related to chromium metabolism in strain HST-98 have been annotated, which helps us to further understand the reduction mechanism of the strain HST-98. In general, Lysinibacillus sp. HST-98 is a potential candidate to repair the Cr(VI)-contaminated sites.

SpacePHARER: sensitive identification of phages from CRISPR spacers in prokaryotic hosts.

SUMMARY: SpacePHARER (CRISPR Spacer Phage-Host Pair Finder) is a sensitive and fast tool for de novo prediction of phage-host relationships via identifying phage genomes that match CRISPR spacers in genomic or metagenomic data. SpacePHARER gains sensitivity by comparing spacers and phages at the protein level, optimizing its scores for matching very short sequences, and combining evidence from multiple matches, while controlling for false positives. We demonstrate SpacePHARER by searching a comprehensive spacer list against all complete phage genomes. AVAILABILITY AND IMPLEMENTATION: SpacePHARER is available as an open-source (GPLv3), user-friendly command-line software for Linux and macOS: https://github.com/soedinglab/spacepharer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than DoxilⓇ.

Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine (BER) and doxorubicin (DOX), which was called LipoBeDo. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, LipoBeDo, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The LipoBeDo significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil (P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.

Gracilibacillus salitolerans sp. nov., a moderate halophile isolated from saline soil in Northwest China.

A moderately halophilic strain, designated SCU50T, was recovered from a saline soil sample and characterized by a polyphasic approach. The 16S rRNA gene sequence analysis showed that strain SCU50T belonged to the genus Gracilibacillus and was most closely related to Gracilibacillus thailandensis TP2-8T (98.1 % similarity) and Gracilibacillus orientalis XH-63T (97.7 %). Genomic average nucleotide identity and digital DNA-DNA hybridization analyses confirmed the separate species status of the new isolate relative to other recognized Gracilibacillus species. The genome size was about 5.09 Mbp and the DNA G+C content was 36.7 mol%. The strain grew optimally at 10-15 % (w/v) NaCl, pH 6.5-7.5 and 25-30 °C. It contained anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0 as the dominant fatty acids and menaquinone-7 as the major respiratory quinone. The polar lipid profile was examined and found to comprise diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid and one unidentified lipid. The cell-wall peptidoglycan type was A1γ based on meso-diaminopimelic acid. Combining the data from phenotypic, chemotaxonomic, genomic and phylogenetic characterization, it was concluded that strain SCU50T should be assigned as representing a novel species within the genus Gracilibacillus. Thus, a novel taxon named Gracilibacillus salitolerans sp. nov. was first established, with SCU50T (=CGMCC 1.17336T=KCTC 43107T) as the type strain.

Preparation, characterization and functional properties of a novel exopolysaccharide produced by the halophilic strain Halomonas saliphila LCB169T.

A novel exopolysaccharide, designated hsEPS, was successfully prepared from the high-salt-fermented broth of a novel species Halomonas saliphila LCB169T by ethanol precipitation, anion-exchange and gel-filtration chromatography, and its structure was well-characterized by means of chemical and spectral analyses. Results showed that hsEPS was primarily composed of mannose and glucose with a relative weight-average molecular weight of 5.133 × 104 g/mol. It was deduced that the major backbone contained (1→2)-linked α-D-Manp and (1→6)-linked α-D-Manp with branches substituted at C-2 by T-α-D-Manp and at C-6 by the fragment of T-α-D-Manp-(1→2)-α-D-Manp-(1→. A sheet-like structure was observed under high magnification. The water solubility index, water holding capacity, oil holding capacity and foaming capacity of hsEPS were 98.0, 19.3, 1386.7 and 82.2%, respectively. It also exhibited outstanding emulsifying activity against all tested edible oils. Together, the resulted data indicated that hsEPS might serve as an active ingredient in food, cosmetics and detergents.

Repurposing antitubercular agent isoniazid for treatment of prostate cancer.

The development of versatile antitumor agents with tumor-imaging, targeting and therapeutic activity is promising for clinical cancer therapy. Prostate cancer is still the one of the leading threats to males. Current therapies have restricted clinical efficiency for patients with advanced and metastatic prostate cancer. Recent studies demonstrate that monoamine oxidase A (MAOA) levels elevate with prostate cancer aggression and metastasis. In addition, MAOA inhibitor therapies have been reported as an effective means to reduce the metastasis of prostate cancer and extend mouse survival. Thus, these findings provide evidence that MAOA is promising for the treatment of metastatic and advanced prostate cancer. Herein, three isoniazid (INH)-dye conjugates were synthesized by conjugating MAOA inhibitor INH with mitochondria-targeting NIRF heptamethine dyes to improve the therapeutic efficacy of prostate cancer. These INH-dye conjugates could accumulate in PC-3 cellular mitochondria via organic anion transport peptide (OATP), increase ROS generation, and induce cancer cells apoptosis. In prostate cancer bearing xenografts, INH-dye conjugates showed significantly improved tumor-homing characteristics, resulting in potent antitumor activity via a reduction in MAOA activity. These results suggest that INH-dye conjugates have great potential to be used as versatile antitumor agents with prostate cancer targeting, NIR imaging, and potent antitumor efficacy.

Self-Assembly of a Pure Photosensitizer as a Versatile Theragnostic Nanoplatform for Imaging-Guided Antitumor Photothermal Therapy.

Imaging-guided diagnosis and phototherapy has been emerging as promising theragnostic strategies for detection and treatment of cancer. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) has been widely investigated for in vivo imaging and photothermal therapy (PTT). However, the tumor-homing ability and PTT efficiency of DiR is greatly limited by its extremely low water solubility and nonspecific distribution in off-target tissues. Herein, a facile nanoassembly of pure DiR is reported as a theragnostic nanocarrier platform for imaging-guided antitumor phototherapy. Self-assembly of DiR has almost no effect on its in vitro photothermal efficacy when compared with DiR solution. Interestingly, the PEGylated nanoassemblies of DiR showed distinct advantages over DiR solution and non-PEGylated nanoassemblies in terms of systemic circulation and tumor-homing capability in vivo. As a result, PEGylated DiR nanoassemblies demonstrate potent photothermal tumor therapy in BALB/c mice bearing 4T1 xenograft tumors. Such a pure photosensitizer-based nanoassembly holds great potential as a versatile platform for efficient imaging-guided cancer therapy.

In vivo tailor-made protein corona of a prodrug-based nanoassembly fabricated by redox dual-sensitive paclitaxel prodrug for the superselective treatment of breast cancer.

Prodrug self-nanoassemblies have many advantages for anticancer drug delivery, including high drug loading rate, resistance to recrystallization, and on-demand drug release. However, few studies have focused on their protein corona, which is inevitably formed after entering the blood and determines their subsequent fates in vivo. To actively tune the protein corona of prodrug nanoassemblies, three maleimide-paclitaxel prodrugs were synthesized via different redox-sensitive linkers (ester bond, thioether bond and disulfide bond). After incubation with rat plasma, the surface maleimide groups effectively captured albumins, resulting in albumin-enriched protein corona. The recruited albumin corona enabled enhanced tumor accumulation and facilitated cellular uptake, ensuring the high-efficiency delivery of nanoassemblies to tumor cells. Surprisingly, we found that the traditionally reduction-sensitive disulfide bond could also be triggered by reactive oxygen species (ROS). Such a redox dual-responsive drug release property of the disulfide bond-containing prodrug nanoassemblies further increased the selectivity in cytotoxicity between normal and tumor cells. Moreover, the disulfide bond-containing prodrug nanoassemblies exhibited the highest antitumor efficacy in vivo compared to marketed Abraxane® and other prodrug nanoassemblies. Thus, the fabrication of the maleimide-decorated disulfide bond bridged prodrug nanoassembly, integrating a tunable protein corona and on-demand drug release, is a promising strategy for improved cancer chemotherapy.

Prostate-Specific Membrane Antigen Targeted Therapy of Prostate Cancer Using a DUPA-Paclitaxel Conjugate.

Prostate cancer (PCa) is the most prevalent cancer among men in the United States and remains the second-leading cause of cancer mortality in men. Paclitaxel (PTX) is the first line chemotherapy for PCa treatment, but its therapeutic efficacy is greatly restricted by the nonspecific distribution in vivo. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most PCa cells, and its expression level increases with cancer aggressiveness, while being present at low levels in normal cells. The high expression level of PSMA in PCa cells offers an opportunity for target delivery of nonspecific cytotoxic drugs to PCa cells, thus improving therapeutic efficacy and reducing toxicity. PSMA has high affinity for DUPA, a glutamate urea ligand. Herein, a novel DUPA-PTX conjugate is developed using DUPA as the targeting ligand to deliver PTX specifically for treatment of PSMA expressing PCa. The targeting ligand DUPA enhances the transport capability and selectivity of PTX to tumor cells via PSMA mediated endocytosis. Besides, DUPA is conjugated with PTX via a disulfide bond, which facilitates the rapid and differential drug release in tumor cells. The DUPA-PTX conjugate exhibits potent cytotoxicity in PSMA expressing cell lines and induces a complete cessation of tumor growth with no obvious toxicity. Our findings give new insight into the PSMA-targeted delivery of chemotherapeutics and provide an opportunity for the development of novel active targeting drug delivery systems for PCa therapy.

Bioresponsive albumin-conjugated paclitaxel prodrugs for cancer therapy.

The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.