A self-assembled pH/enzyme dual-responsive prodrug with PEG deshielding for multidrug-resistant tumor therapy

2020 ◽  
Vol 8 (6) ◽  
pp. 1290-1301 ◽  
Author(s):  
Ronghua Ni ◽  
Jianhua Zhu ◽  
Zhiyuan Xu ◽  
Yun Chen
Keyword(s):  
Multidrug Resistance ◽  
Tumor Therapy ◽  
Multidrug Resistant ◽  
Dual Responsive ◽  
Self Assembled

Multidrug resistance (MDR) is one of the major obstacles for tumor therapy.

scholarly journals 130. increase in Multidrug Resistance (2011–2018) and the Emergence of Extensive Drug Resistance (2020) in shigella Sonnei in the United States

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S195-S195
Author(s):  
Naeemah Z Logan ◽  
Beth E Karp ◽  
Kaitlin A Tagg ◽  
Claire Burns-Lynch ◽  
Jessica Chen ◽  
...  
Keyword(s):  
United States ◽  
Multidrug Resistance ◽  
Disease Surveillance ◽  
Sequence Data ◽  
The United States ◽  
Multidrug Resistant ◽  
Shigella Sonnei ◽  
Short Read ◽  
Men 2 ◽  
The Us

Abstract Background Multidrug-resistant (MDR) Shigella sonnei infections are a serious public health threat, and outbreaks are common among men who have sex with men (MSM). In February 2020, Australia’s Department of Health notified CDC of extensively drug-resistant (XDR) S. sonnei in 2 Australian residents linked to a cruise that departed from Florida. We describe an international outbreak of XDR S. sonnei and report on trends in MDR among S. sonnei in the United States. Methods Health departments (HDs) submit every 20th Shigella isolate to CDC’s National Antimicrobial Resistance Monitoring System (NARMS) laboratory for susceptibility testing. We defined MDR as decreased susceptibility to azithromycin (MIC ≥32 µg/mL) with resistance to ampicillin, ciprofloxacin, and cotrimoxazole, and XDR as MDR with additional resistance to ceftriaxone. We used PulseNet, the national subtyping network for enteric disease surveillance, to identify US isolates related to the Australian XDR isolates by short-read whole genome sequencing. We screened these isolates for resistance determinants (ResFinder v3.0) and plasmid replicons (PlasmidFinder) and obtained patient histories from HDs. We used long-read sequencing to generate closed plasmid sequences for 2 XDR isolates. Results NARMS tested 2,781 S. sonnei surveillance isolates during 2011–2018; 80 (2.9%) were MDR, including 1 (0.04%) that was XDR. MDR isolates were from men (87%), women (9%), and children (4%). MDR increased from 0% in 2011 to 15.3% in 2018 (Figure). In 2020, we identified XDR isolates from 3 US residents on the same cruise as the Australians. The US residents were 41–42 year-old men; 2 with available information were MSM. The US and Australian isolates were highly related (0–1 alleles). Short-read sequence data from all 3 US isolates mapped to the blaCTX-M-27 harboring IncFII plasmids from the 2 Australian isolates with >99% nucleotide identity. blaCTX-M-27 genes confer ceftriaxone resistance. Increase in Percentage of Shigella sonnei Isolates with Multidrug Resistance* in the United States, 2011–2018† Conclusion MDR S. sonnei is increasing and is most often identified among men. XDR S. sonnei infections are emerging and are resistant to all recommended antibiotics, making them difficult to treat without IV antibiotics. This outbreak illustrates the alarming capacity for XDR S. sonnei to disseminate globally among at-risk populations, such as MSM. Disclosures All Authors: No reported disclosures

scholarly journals Genomic Characterization of New Variant of Hydrogen Sulfide (H2S)-Producing Escherichia coli with Multidrug Resistance Properties Carrying the mcr-1 Gene in China

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Author(s):  
Silpak Biswas ◽  
Mohammed Elbediwi ◽  
Guimin Gu ◽  
Min Yue
Keyword(s):  
Escherichia Coli ◽  
Hydrogen Sulfide ◽  
Multidrug Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Colistin Resistance ◽  
New Variant ◽  
Genomic Characterization ◽  
Human Infections

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

Nanomaterials combine multiple therapeutic approaches for cancer cell multidrug resistance, ferroptotic cell death is promising in various cancers

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Cell Death ◽  
Multidrug Resistance ◽  
Cancer Cell ◽  
High Efficiency ◽  
New Technologies ◽  
Multidrug Resistant ◽  
Therapeutic Approaches ◽  
Combination Strategies ◽  
New Strategy ◽  
Chemotherapy Patients

Cancer cell multidrug resistance (MDR) is one of the most significant barriers to chemotherapy patients' ability to treat malignant tumors.This review first discusses the basic processes of MDR and then details the newest usage of nanomaterials combining multiple therapeutic approaches (e.g. PDT, PTT, gas therapy, gene therapy, and CDT) with MDR chemotherapy. We also analyze the advantages and rationales of these combination systems and why they can reduce MDR cancer cells. Currently, together with various new treatment approaches, MDR-related chemotherapeutic research is gaining momentum in search of better therapeutic results. PDT, for example, has the ability to eliminate high-efficiency multidrug-resistant malignancies but has limited relevance to tumor treatment. In this perspective, SDT is a highly promising approach as it increases ROS production utilizing ultrasonic vibrations, allowing magnitude orders to reach deeper than light. PTT is also often criticized for NIR light's restricted penetration depth; thermomagnetic therapy, using magnetic fields to produce local tissue hyperthermia, can considerably alleviate this problem. However, current research on the possibilities of using these new technologies to fight MDR remains rather rare, and more combination strategies should be carefully investigated in the future. Moreover, ongoing discoveries of cell death pathways, highlighted by recent ferroptosis findings, present a new strategy for our battle against MDR and may revolutionize our knowledge of MDR formation. Ferroptotic cell death promises to treat MDR in various cancers. While most of this cutting-edge research is still in its infancy, we anticipate gaining a deeper understanding of the effectiveness of these revolutionary anti-MDR medicines in the near future.

Reversal of Multidrug Resistance by Mitochondrial Targeted Self-Assembled Nanocarrier Based on Stearylamine

2013 ◽  
Vol 10 (6) ◽  
pp. 2426-2434 ◽  
Author(s):  
Zhiwen Zhang ◽  
Zeying Liu ◽  
Li Ma ◽  
Shijun Jiang ◽  
Yixin Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Self Assembled

scholarly journals The Fluorescent Probe Bodipy-FL-Verapamil Is a Substrate for Both P-glycoprotein and Multidrug Resistance-related Protein (MRP)-1

2002 ◽  
Vol 50 (5) ◽  
pp. 731-734 ◽  
Author(s):  
Enrico Crivellato ◽  
Luigi Candussio ◽  
Anna M. Rosati ◽  
Fiora Bartoli-Klugmann ◽  
Franco Mallardi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Drug Transport ◽  
Mrna Level ◽  
Fluorescent Microscopy ◽  
Flow Cytometric Analysis ◽  
Cell Types ◽  
Multidrug Resistant ◽  
Related Protein ◽  
P Glycoprotein ◽  
Multidrug Resistance Related Protein

Several fluorescent probes have been used in functional studies to analyze drug transport in multidrug-resistant cells by fluorescent microscopy. Because many of these molecules have some drawbacks, such as toxicity, nonspecific background, or accumulation in mitochondria, new fluorescent compounds have been proposed as more useful tools. Among these substances, Bodipy-FL-Verapamil, a fluorescent conjugate of the drug efflux blocker verapamil, has been used to study P-glycoprotein activity in different cell types. In this study we tested by fluorescent microscopy the accumulation of Bodipy-FL- Verapamil in cell lines that overexpress either P-glycoprotein (P-gp) or multidrug resistance-related protein 1 (MRP1). Expression of P-gp and MRP1 was evaluated at the mRNA level by RT-PCR technique and at the protein level by flow cytometric analysis using C219 and MRP-m6 monoclonal antibodies. Results indicate that Bodipy-FL-Verapamil is actually a substrate for both proteins. As a consequence, any conclusion about P-gp activity obtained by the use of Bodipy-FL-Verapamil as fluorescent tracer should be interpreted with caution.

scholarly journals Multidrug resistance in Shiga toxin-producing Escherichia coli (STEC) isolated from broiler chickens at slaughter

2021 ◽  
Vol 42 (6supl2) ◽  
pp. 3813-3824
Author(s):  
Rodrigo Pacheco Ornellas ◽  
◽  
Hugo Peralva Lopes ◽  
Daniela de Queiroz Baptista ◽  
Thomas Salles Dias ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Shiga Toxin ◽  
Broiler Chickens ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Public Health Issue ◽  
Resistant Bacteria ◽  
Systemic Complications

Broiler chickens and derived products are a key source of Shiga toxin-producing Escherichia coli (STEC) in humans. This pathotype is responsible for causing severe episodes of diarrhea, which can progress to systemic complications. A rapid and accurate diagnosis of the disease, and early treatment of the infection with antimicrobials, can prevent it worsening. However, multidrug-resistant strains have potentially negative implications for treatment success. In this context, the aim of the present study was to isolate and identify multidrug-resistant STEC strains from broiler chickens and carcasses. Of 171 E. coli strains, isolated by conventional microbiological techniques and submitted to Polymerase Chain Reaction (PCR), for detection of stx1 and stx2 genes, 21.05% (36/171) were STEC pathotype, and most of them (66.67% - 24/36) carried both stx1 and eae genes. The multidrug resistance pattern was observed in 75% (27/36) of STEC strains. The presence of STEC in broiler chickens and carcasses reinforces that these sources may act as reservoirs for this pathotype. Multidrug-resistant bacteria contaminating animal products represent a public health issue because of the possibility of spread of multidrug-resistant determinants in the food chain and a higher risk of failure in human treatment when antimicrobials are needed.

scholarly journals Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Heng Mei ◽  
Jing Li ◽  
Shengsheng Cai ◽  
Xuequan Zhang ◽  
Wenqiang Shi ◽  
...  
Keyword(s):  
Drug Loading ◽  
Tumor Therapy ◽  
Ros Generation ◽  
Drug Conjugates ◽  
Tocopheryl Succinate ◽  
Carrier Free ◽  
Negative Surface ◽  
Inert Carrier ◽  
Self Assembled

Abstract Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.

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