Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification

Barros, André Luís Branco de; Mota, Luciene das Graças; Soares, Daniel Crístian Ferreira; Coelho, Marina Melo Antunes; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

doi:10.1016/j.bmcl.2011.10.016

Cited by 27 publications

(18 citation statements)

References 17 publications

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“…BnR-agonists coupled to liposomes and 99m Tc showed high specificity/selectivity for imaging breast-cancer-cells in tumor-bearing nude-mice[97]. BnR-peptide-agonist ligands have been coupled to liposomes, which can, when loaded with doxorubicin or other cytotoxic-agents, demonstrate specific cytotoxicity for cancer-cells[98–102].…”

Section: Imaging and Targeted-delivery Of Cytotoxic-agents To Neopmentioning

confidence: 99%

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Moreno

Ramos-Álvarez

Moody

et al. 2016

Expert Opinion on Therapeutic Targets

102

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Introduction Despite remarkable advances in tumor treatment, many patients still die from common tumors (breast, prostate, lung, CNS, colon, and pancreas), and thus, new approaches are needed. Many of these tumors synthesize bombesin (Bn)-related peptides and over-express their receptors (BnRs), hence functioning as autocrine-growth-factors. Recent studies support the conclusion that Bn-peptides/BnRs are well-positioned for numerous novel antitumor treatments, including interrupting autocrine-growth via the use of over-expressed receptors for imaging and targeting cytotoxic-compounds, either by direct-coupling or combined with nanoparticle-technology. Areas covered The unique ability of common neoplasms to synthesize, secrete, and show a growth/proliferative/differentiating response due to BnR over-expression, is reviewed, both in general and with regard to the most frequently investigated neoplasms (breast, prostate, lung, and CNS). Particular attention is paid to advances in the recent years. Also considered are the possible therapeutic approaches to the growth/differentiation effect of Bn-peptides, as well as the therapeutic implication of the frequent BnR over-expression for tumor-imaging and/or targeted-delivery. Expert opinion Given that Bn-related-peptides/BnRs are so frequently ectopically-expressed by common tumors, which are often malignant and become refractory to conventional treatments, therapeutic interventions using novel approaches to Bn-peptides and receptors are being explored. Of particular interest is the potential of reproducing BnRs in common tumors, such as the recent success of utilizing overexpression of somatostatin-receptors by neuroendocrine-tumors to provide the most sensitive imaging methods and targeted delivery of cytotoxic-compounds.

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Section: Imaging and Targeted-delivery Of Cytotoxic-agents To Neopmentioning

confidence: 99%

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Moreno

Ramos-Álvarez

Moody

et al. 2016

Expert Opinion on Therapeutic Targets

102

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“…The former is obtained by the inoculation of tumor cells from the own animal species used while xenograft models are developed by the inoculation of tumor cells from other species, such as human tumor cells [23–25]. Both allograft and xenograft tumor models have been used for the development of radiolabeled BBN derivatives, specifically the inoculation of Ehrlich cells (murine breast cancer cells) in Swiss mice (allograft model) [26,27], and the inoculation of MDA-MB-231 cells (human breast cancer cells) in athymic nu/nu mice (xenograft model) [28]. It is important to mention that xenograft inoculation requires the use of immune-compromised animals, such as nude mice (T-cells deficiency) and severe combined immunodeficiency (SCID) mice (T-and B-cells deficiency), in order to avoid cancer cells rejection and to assure tumors development.…”

Section: Tumors Overexpressing Bombesin Receptors and Animal Modelsmentioning

confidence: 99%

Radiolabeled bombesin derivatives for preclinical oncological imaging

Ferreira

Fuscaldi

Townsend

et al. 2017

Biomedicine & Pharmacotherapy

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Despite efforts, cancer is still one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths each year, according to the World Health Organization. Among the strategies to reduce cancer progression and improving its management, implementing early detection technologies is crucial. Based on the fact that several types of cancer cells overexpress surface receptors, small molecule ligands, such as peptides, have been developed to allow tumor identification at earlier stages. Allied with imaging techniques such as PET and SPECT, radiolabeled peptides play a pivotal role in nuclear medicine. Bombesin, a peptide of 14 amino acids, is an amphibian homolog to the mammalian gastrin-releasing peptide (GRP), that has been extensively studied as a targeting ligand for diagnosis and therapy of GRP positive tumors, such as breast, pancreas, lungs and prostate cancers. In this context, herein we provide a review of reported bombesin derivatives radiolabeled with a multitude of radioactive isotopes for diagnostic purposes in the preclinical setting. Moreover, since animal models are highly relevant for assessing the potential of clinical translation of this radiopeptides, a brief report of the currently used GRP-positive tumor-bearing animal models is described.

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“…The vials were then frozen in boiling nitrogen and placed on the plate of a ModulyoD freeze-dryer (Thermo Electron Corporation, USA) at room temperature and a vacuum level of 10 −1 atm. The condenser temperature was maintained at − 45 C. The drying process took 24 h. After this period, the freeze-dried liposomes were reconstituted with a fresh solution of 99m Tc-BBN 7-14 , as previously described, 19 and the mean diameter of the vesicles was determined. Samples of the freeze-dried liposomes in the presence of glucose (SpHLG) at a cryoprotectant: phospholipid ratio (w/w) of 2:1, after reconstitution with a solution of 99m Tc-BBN 7-14 (SpHLG-99m Tc-BBN 7-14 were used to perform the subsequent in vivo assays.…”

Section: Size Distribution and Zeta Potentialmentioning

confidence: 99%

“…Liposomes, in particular, can be used to encapsulate peptides such as bombesin (in the hydrophilic core), thereby avoiding peptide degradation by plasmatic enzymes and yielding a better outcome, e.g., higher signalto-noise ratio. 19 Liposomes are spherical vesicles that are formed when phospholipids are exposed to an aqueous environment. They can be used to encapsulate and deliver hydrophilic and lipophilic substances.…”

Section: Introductionmentioning

confidence: 99%

Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification

Barros¹,

Ld²,

Mm³

et al. 2015

j biomed nanotechnol

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Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. These receptors are over-expressed in several forms of cancer; radiolabeled BBN could therefore be used to detect such cancers. However, the degradation of peptides is a critical issue in the development of tumor tracers. Liposomes can be used to overcome this problem and improve the uptake of tracers by tumors. Therefore, the purpose of this study was to prepare and characterize long-circulating and pH-sensitive liposomes (SpHL) containing 99m Tc-HYNIC-Ala-Bombesin 7-14 ( 99m Tc-BBN 7-14 ). In addition, the ability of this system to identify human breast cancer tissue was evaluated using biodistribution studies and scintigraphic images. Long-circulating and pH-sensitive liposomes (SpHL) were prepared and freeze-dried in the presence of cryoprotectants (glucose, mannitol, and trehalose). They were subsequently reconstituted with a solution of 99m Tc-HYNIC-Ala-Bombesin 7-14 ( 99m Tc-BBN 7-14 ). The liposomes were evaluated for size, encapsulation percentage, radiotracer leakage, and storage stability. In addition, in vivo studies were performed in breast tumor-bearing nude mice. Liposomes in the presence of glucose (SpHLG), exhibited a mean diameter of 164.5 ± 6.5 nm and exhibited a 99m Tc-BBN 7-14 encapsulation percentage of 30%. In addition, they remained highly stable for up to 120 days of storage. SpHLG99m Tc-BBN 7-14 showed longer blood circulation than free 99m Tc-BBN 7-14 did. The tumor-to-muscle and tumor-to-blood ratios for SpHLG-99m Tc-BBN 7-14 were high at 4 h post-injection (9.31%ID/g and 7.93%ID/g, respectively). Furthermore, scintigraphic images revealed a strong signal in the tumor area, indicating tumor specificity of SpHLG-99m Tc-BBN 7-14 . In summary, SpHLG-99m Tc-BBN 7-14 presented characteristics suitable for a diagnostic agent, and is a potential tool for tumor identification.

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Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification

Cited by 27 publications

References 17 publications

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

Radiolabeled bombesin derivatives for preclinical oncological imaging

Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification

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