Coordinating bioorthogonal reactions with two tumor-microenvironment-responsive nanovehicles for spatiotemporally controlled prodrug activation

Spatiotemporally controlled activation: Dox-TCO loaded low pH-sensitive nanovehicles and Tz-containing MMP-2-sensitive nanocarriers simultaneously dissociated in tumor microenvironment, with Dox locally liberated through IEDDA biorthogonal reaction.

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Double pH-sensitive Nanotheranostics of Polypeptide Nanoparticle-Encapsulated BODIPY with Both NIR Activated Fluorescence and Enhanced Photodynamic Therapy

Journal of Materials Chemistry B ◽

10.1039/d1tb01768c ◽

2021 ◽

Author(s):

Huiping Dang ◽

Quan Cheng ◽

Youliang Tian ◽

Changchang Teng ◽

Kai Xie ◽

...

Keyword(s):

Photodynamic Therapy ◽

Tumor Microenvironment ◽

Cancer Therapy ◽

Fluorescence Imaging ◽

Intelligent Systems ◽

Ph Sensitive ◽

Nir Fluorescence

To achieve accurate fluorescence imaging-guided cancer therapy, intelligent systems with specific responsiveness to the tumor microenvironment need to be designed. Here, we have achieved both enhanced NIR fluorescence and photodynamic...

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A General Strategy for Macrotheranostic Prodrug Activation: Synergy between the Acidic Tumor Microenvironment and Bioorthogonal Chemistry

Angewandte Chemie ◽

10.1002/ange.201913522 ◽

2020 ◽

Vol 132 (18) ◽

pp. 7235-7239 ◽

Cited By ~ 1

Author(s):

Yansong Dong ◽

Yalan Tu ◽

Kewei Wang ◽

Congfei Xu ◽

Youyong Yuan ◽

...

Keyword(s):

Tumor Microenvironment ◽

General Strategy ◽

Bioorthogonal Chemistry ◽

Prodrug Activation

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Involvement of the HP0165-HP0166 Two-Component System in Expression of Some Acidic-pH-Upregulated Genes of Helicobacter pylori

Journal of Bacteriology ◽

10.1128/jb.188.5.1750-1761.2006 ◽

2006 ◽

Vol 188 (5) ◽

pp. 1750-1761 ◽

Cited By ~ 30

Author(s):

Yi Wen ◽

Jing Feng ◽

David R. Scott ◽

Elizabeth A. Marcus ◽

George Sachs

Keyword(s):

Helicobacter Pylori ◽

Sequence Similarity ◽

Low Ph ◽

Ph Sensitive ◽

Cytoplasmic Ph ◽

Two Component System ◽

Mobility Shift ◽

Component System ◽

Two Component

ABSTRACT About 200 genes of the gastric pathogen Helicobacter pylori increase expression at medium pHs of 6.2, 5.5, and 4.5, an increase that is abolished or much reduced by the buffering action of urease. Genes up-regulated by a low pH include the two-component system HP0165-HP0166, suggesting a role in the regulation of some of the pH-sensitive genes. To identify targets of HP0165-HP0166, the promoter regions of genes up-regulated by a low pH were grouped based on sequence similarity. Probes for promoter sequences representing each group were subjected to electrophoretic mobility shift assays (EMSA) with recombinant HP0166-His6 or a mutated response regulator, HP0166-D52N-His6, that can specifically determine the role of phosphorylation of HP0166 in binding (including a control EMSA with in-vitro-phosphorylated HP0166-His6). Nineteen of 45 promoter-regulatory regions were found to interact with HP0166-His6. Seven promoters for genes encoding α-carbonic anhydrase, omp11, fecD, lpp20, hypA, and two with unknown function (pHP1397-1396 and pHP0654-0675) were clustered in gene group A, which may respond to changes in the periplasmic pH at a constant cytoplasmic pH and showed phosphorylation-dependent binding in EMSA with HP0166-D52N-His6. Twelve promoters were clustered in groups B and C whose up-regulation likely also depends on a reduction of the cytoplasmic pH at a medium pH of 5.5 or 4.5. Most of the target promoters in groups B and C showed phosphorylation-dependent binding with HP0166-D52N-His6, but promoters for ompR (pHP0166-0162), pHP0682-0681, and pHP1288-1289 showed phosphorylation-independent binding. These findings, combined with DNase I footprinting, suggest that HP0165-0166 is an acid-responsive signaling system affecting the expression of pH-sensitive genes. Regulation of these genes responds either to a decrease in the periplasmic pH alone (HP0165 dependent) or also to a decrease in the cytoplasmic pH (HP0165 independent).

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A Humanized Immunoenzyme with Enhanced Activity for Glucuronide Prodrug Activation in the Tumor Microenvironment

Bioconjugate Chemistry ◽

10.1021/bc1005784 ◽

2011 ◽

Vol 22 (5) ◽

pp. 938-948 ◽

Cited By ~ 18

Author(s):

Kai-Chuan Chen ◽

Shih-Yen Wu ◽

Yu-Lin Leu ◽

Zeljko M. Prijovich ◽

Bing-Mae Chen ◽

...

Keyword(s):

Tumor Microenvironment ◽

Prodrug Activation ◽

Enhanced Activity

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Studying the anticancer activity in vitro of doxorubicin-encapsulated pH-sensitive redox nanoparticles

Ministry of Science and Technology, Vietnam ◽

10.31276/vjst.63(5).22-28 ◽

2021 ◽

Vol 63 (5) ◽

pp. 22-28

Author(s):

Thi Hoang Nguyen ◽

◽

Nhu Thuy Trinh ◽

Binh Long Vong ◽

◽

...

Keyword(s):

Cancer Cells ◽

Chemotherapeutic Agent ◽

Low Ph ◽

Ph Sensitive ◽

Coated Nanoparticles ◽

Specific Distribution ◽

Application Potential ◽

Ph Conditions ◽

Mcf 7

Doxorubicin (DOX) is known as a chemotherapeutic agent for treating a variety of cancers. However, due to non-specific distribution, DOX causes severe side effects, leading to the limitation of its clinical application. In this study, pH-sensitive redox nanoparticles containing DOX were studied to form drug-coated nanoparticles with the size of about 40-60 nm that increases the concentration of drugs accumulated at the tumor site in response to low pH conditions. The optimal properties of the nanoparticles were investigated by analysing the antioxidant activity, sensitivity to pH, drug delivery in a low pH environment, and toxicity on cancer cells, thereby observing the possibility of inhibiting the migration of cancer cells. Results showed that the combination of DOX and the pH-sensitive redox nanoparticles not only increases anticancer in colorectal cancer (C-26), breast cancer (MCF-7) but also reduces bovine aorta endothelial cells (BAEC) and inhibits C-26 cell migration in vitro.Thepaper results reveal the application potential of the pH-sensitive redox nanoparticles in improving the effectiveness of cancer treatment.

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Abstract 2867: Delivery of immunomodulators to the acidic tumor microenvironment by ultra-pH sensitive nanoparticle technology

10.1158/1538-7445.am2020-2867 ◽

2020 ◽

Author(s):

Xinliang Ding ◽

Jason Miller ◽

Ashley Campbell ◽

Jonathan Almazan ◽

Stephen Gutowski ◽

...

Keyword(s):

Tumor Microenvironment ◽

Ph Sensitive

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Targeting Cell-Impermeable Prodrug Activation to Tumor Microenvironment Eradicates Multiple Drug-Resistant Neoplasms

Cancer Research ◽

10.1158/0008-5472.can-05-2591 ◽

2006 ◽

Vol 66 (2) ◽

pp. 970-980 ◽

Cited By ~ 79

Author(s):

Wenyuan Wu ◽

Yunping Luo ◽

Chengzao Sun ◽

Yuan Liu ◽

Paul Kuo ◽

...

Keyword(s):

Tumor Microenvironment ◽

Multiple Drug ◽

Drug Resistant ◽

Prodrug Activation ◽

Multiple Drug Resistant

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pH-Sensitive Polymers for Novel Conformance-Control and Polymer-Flood Applications

SPE Reservoir Evaluation & Engineering ◽

10.2118/121686-pa ◽

2010 ◽

Vol 13 (06) ◽

pp. 926-939 ◽

Cited By ~ 19

Author(s):

Suk Kyoon Choi ◽

Mukul M. Sharma ◽

Steven L. Bryant ◽

Chun Huh

Keyword(s):

Polymer Solution ◽

Polymer Concentration ◽

Injection Pressure ◽

Low Ph ◽

Ph Sensitive ◽

Solution Viscosity ◽

Conformance Control ◽

Polymer Flood ◽

Geochemical Reactions ◽

Acidic Conditions

Summary Novel conformance-control and polymer-flood applications that exploit the pH sensitivity of partially hydrolyzed polyacrylamide (HPAM) are proposed. The key feature of this process is the injection of the HPAM solution under acidic conditions. The low pH makes polymer molecules coil tightly, resulting in a very low polymer-solution viscosity. This allows the polymer solution to be injected into the reservoir at a substantially reduced injection pressure. Once injected, the acid reacts with the formation minerals to cause a spontaneous pH increase, uncoiling the polymer chains and causing a large increase in solution viscosity. Such a viscosity-control scheme can be exploited for placement of a concentrated polymer solution in high-permeability zones, where it later viscosifies to divert subsequently injected fluids (in-depth conformance control), or to reduce the high pressure drop near the wellbore during polymer injection (injectivity improvement). Extensive laboratory experiments were systematically performed and interpreted to evaluate the novel applications of pH-sensitive HPAM. The evaluations require (a) quantification of steady-shear viscosities, (b) characterization of geochemical reactions with acids, and (c) transport evaluation of HPAM solutions in cores. Rheological measurements show that shear viscosities of HPAM solution have a pronounced, but reversible, dependence on pH. The peak pHs observed in several shut-ins guarantee that spontaneous geochemical reactions can return the polymer solution to its original high viscosity. The use of a weak acid is the key. Coreflood results show that the HPAM solution under acidic conditions can be propagated through cores with much higher mobility than at neutral pH. However, low-pH conditions increase adsorption (polymer loss) and require additional chemical cost (for acid). The optimum injection formulation (polymer concentration, injection pH) will depend on the specific reservoir mineralogy, permeability, salinity, and injection conditions.

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pH Tunable Turn on and Turn off Quantum Dots Conjugated with Poly(2-(Dialkylamino)ethyl Methacrylate)

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.998-999.75 ◽

2014 ◽

Vol 998-999 ◽

pp. 75-78

Author(s):

Xian Nan Huang ◽

Wei Li ◽

Wei He

Keyword(s):

Ph Value ◽

Aqueous Media ◽

Low Ph ◽

Ph Sensitive ◽

Cds Nanoparticles ◽

Ethyl Methacrylate ◽

Turn On ◽

Target Imaging ◽

Application Potential ◽

Amine Groups

A novel pH sensitive cadmium sulfide quantum dot (CdS QD) was prepared by a coprecipitation method in the presence of pH sensitive poly (2-(dimethylamino) ethyl methacrylate)-co-poly (2-(dibutylamino) ethyl methacrylate)(PDMA-PDBA) copolymer. CdCl2and Na2S were mixed in aqueous media in the presence of PDMA-PDBA. The amine groups of PDMA were anchored on the surface of the formed CdS nanoparticles, whereas the PDBA segment was anchored on the surface to form a hydrophilic palisade at low pH environment, thus turn on the fluorescence CdS QD probe; at high pH value, PDBA segments precipitate and turn off fluorescence because of the phase separation. This novel pH sensitive fluorescene CdS QDs probe have great application potential for target imaging of cancer.

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