Effect of Retro‐Inverso Isomer of Bradykinin on Size‐Dependent Penetration of Blood–Brain Tumor Barrier

Su, Bingxia; Wang, Ruifeng; Xie, Zuoxu; Ruan, Huitong; Li, Jichen; Xie, Conghua; Lu, Weiyue; Wang, Jing; Wang, Dongli; Liu, Min

doi:10.1002/smll.201702331

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…Therefore, researchers developed various methods to augment the EPR effect via modulating many factors, such as bradykinin, nitric oxide, prostaglandins, etc. [132][133][134][135][136]. NO, as a major endothelium-dependent vasodilator produced by large blood vessels, can regulate microvascular blood flow and vascular permeability [137].…”

Section: Augmented Epr Effects By the No Drug Delivery Systemmentioning

confidence: 99%

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Wang

Xie

et al. 2020

Cancers

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Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.

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Section: Augmented Epr Effects By the No Drug Delivery Systemmentioning

confidence: 99%

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Wang

Xie

et al. 2020

Cancers

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“…Retroinverso analog of the neurotrophic peptide, prosaptide, not only retains the bioactivity and blood‐brain barrier permeability but it is also less prone to proteolysis and thereby more effective for the treatment of neurodegenerative disease, whereas inverso analog of this peptide has no activity (Taylor, Otero, Banks, & O'Brien, ). Compared to bradykinin, its retroinverso analog is found to have better blood‐brain barrier permeability and higher affinity for target receptor BK type 2 (Su et al., ). Similarly, D VS is a retroinverso analog of VS peptide which has higher stability and exceptional efficacy in targeting glioma cells by binding to integrins (Li et al., ; Ren et al., ; Su et al., ).…”

Section: Experimental Attempts Of Mimetics Using Retroinverso and Modmentioning

confidence: 99%

“…Compared to bradykinin, its retroinverso analog is found to have better blood‐brain barrier permeability and higher affinity for target receptor BK type 2 (Su et al., ). Similarly, D VS is a retroinverso analog of VS peptide which has higher stability and exceptional efficacy in targeting glioma cells by binding to integrins (Li et al., ; Ren et al., ; Su et al., ). Retroinverso C‐end rule (CendR) peptide D(RPPREGR) has been used to targeted delivery of a gene to glioma cells.…”

Section: Experimental Attempts Of Mimetics Using Retroinverso and Modmentioning

confidence: 99%

Peptide and protein mimetics by retro and retroinverso analogs

Rai

2019

Chem Biol Drug Des

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Retroinverso analog of a natural polypeptide can sometimes mimic the structure and function of the natural peptide. The additional advantage of using retroinverso analog is that it is resistant to proteolysis. The retroinverso analogs have peptide sequence in reverse direction with respect to natural peptide and also have chirality of amino acid inverted from L to D. The D amino acids cannot be recognized by common proteases of the body; therefore, these peptides will not be degraded easily and have a longer‐lasting effect as vaccine and inhibitor drugs. There have been many contested propositions about the geometric relationship between a peptide and its retro, inverso, or retroinverso analog. A retroinverso analog sometimes fails to adopt the structure that can mimic the function of the natural peptide. In such cases, partial retroinverso analog and other modifications can help in achieving the desired structure and function. Here, we review the theory, major experimental attempts, prediction methods, and alternative strategies related to retroinverso peptidomimetics.

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“…This could be achieved following co-administration of drug-loaded NPs with free forms of kinin B1R or B2R agonist or with kinins-functionalized (-liganded) NPs containing drugs. These are ongoing studies in our laboratories and some reports on this have been published [ 31 , 32 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

et al. 2020

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The blood–brain barrier (BBB) is a major obstacle to the development of effective diagnostics and therapeutics for brain cancers and other central nervous system diseases. Peptide agonist analogs of kinin B1 and B2 receptors, acting as BBB permeabilizers, have been utilized to overcome this barrier. The purpose of the study was to provide new insights for the potential utility of kinin analogs as brain drug delivery adjuvants. In vivo imaging studies were conducted in various animal models (primary/secondary brain cancers, late radiation-induced brain injury) to quantify BBB permeability in response to kinin agonist administrations. Results showed that kinin B1 (B1R) and B2 receptors (B2R) agonists increase the BBB penetration of chemotherapeutic doxorubicin to glioma sites, with additive effects when applied in combination. B2R agonist also enabled extravasation of high-molecular-weight fluorescent dextrans (155 kDa and 2 MDa) in brains of normal mice. Moreover, a systemic single dose of B2R agonist did not increase the incidence of metastatic brain tumors originating from circulating breast cancer cells. Lastly, B2R agonist promoted the selective delivery of co-injected diagnostic MRI agent Magnevist in irradiated brain areas, depicting increased vascular B2R expression. Altogether, our findings suggest additional evidence for using kinin analogs to facilitate specific access of drugs to the brain.

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Effect of Retro‐Inverso Isomer of Bradykinin on Size‐Dependent Penetration of Blood–Brain Tumor Barrier

Cited by 25 publications

References 34 publications

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer

Peptide and protein mimetics by retro and retroinverso analogs

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

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