Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Beata Paulina Rurarz
 -- 2535 2023-02-24 22:53:24 |
2 format correct
Jessie Wu
 + 3 word(s) 2538 2023-02-27 02:27:30 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Rurarz, B.P.; Bukowczyk, M.; Gibka, N.; Piastowska-Ciesielska, A.W.; Karczmarczyk, U.; Ulański, P. Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems. Encyclopedia. Available online: https://encyclopedia.pub/entry/41650 (accessed on 27 July 2024).
Rurarz BP, Bukowczyk M, Gibka N, Piastowska-Ciesielska AW, Karczmarczyk U, Ulański P. Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems. Encyclopedia. Available at: https://encyclopedia.pub/entry/41650. Accessed July 27, 2024.
Rurarz, Beata Paulina, Małgorzata Bukowczyk, Natalia Gibka, Agnieszka Wanda Piastowska-Ciesielska, Urszula Karczmarczyk, Piotr Ulański. "Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems" Encyclopedia, https://encyclopedia.pub/entry/41650 (accessed July 27, 2024).
Rurarz, B.P., Bukowczyk, M., Gibka, N., Piastowska-Ciesielska, A.W., Karczmarczyk, U., & Ulański, P. (2023, February 24). Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems. In Encyclopedia. https://encyclopedia.pub/entry/41650
Rurarz, Beata Paulina, et al. "Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems." Encyclopedia. Web. 24 February, 2023.
Gastrin-Releasing Peptide Receptor  Targeting and Nanosystems
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms24043455

Advances in nanomedicine bring the attention of researchers to the molecular targets that can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical, and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands as well as methods of their incorporation with the various delivery vehicles have been described in the literature. Proper design allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities.

GRPR bombesin nanoparticle liposome gold nanoparticle

1. Introduction

As gastrin-releasing peptide receptor (GRPR) is well acknowledged to be overexpressed in cancers, it attracts the attention of scientists dealing with novel delivery systems based on active targeting, where GRPR ligands are used as moieties able to lead to preferential accumulation of the nanoparticles in the sites of interest. These nanoparticles may act as drug delivery vehicles, so they deliver cytotoxic biological activity in the tumor site. On the other hand, detectable nanoparticles can be tracked in the human body using different imaging modalities, hence helping with cancer localization and staging. Finally, both these activities can be incorporated into one construct and act as theranostic, the idea derived from the personalized medicine approach, which connects oncological diagnostics and treatment at the same time. During the design of a targeted nanoformulation, fundamentally, three vital points need to be initially considered: the choice of the proper targeting ligand, the type of nanoparticles, and the means of bringing those together (Figure 1). These three aspects need to be fine-tuned to allow the successful development of nanosystems with anticipated properties and activity, particularly with respect to the desired mode of operation: therapeutic, diagnostic, or, combining both, theranostic (Figure 1).
Ijms 24 03455 g003 550
Figure 1. Targeted nanosystems may perform different roles, but, fundamentally, three major aspects, carrier nanoparticle, targeting ligand, and means of bringing them together, must be fine-tuned to yield successful formulation. Created with BioRender.com.
There are certain trends that are noticeable in GRPR nanotargeting research. This receptor is overexpressed in numerous cancers, i.e., breast, colon, glioblastoma, head and neck squamous cell, lung, neuroblastoma, pancreatic, and prostate [1]. However, the vast majority (ca. 70%) of the published studies concerning the use of nanosystems focus on applications in prostate or breast cancer research. It seems coherent, though, with the public health data pointing out that those malignancies are (next to colon and rectum) in the top three of cancer prevalence by type worldwide [2]. However, when considering the type of nanoparticles exploited in the GRPR targeting research, almost half of the formulations are based on either gold nanostructures or liposomal/micellar vesicles, which are predominantly exploited in imaging and therapy, respectively. Those trends also seem well grounded, since, out of 25 clinically approved nanoformulations (U.S. Food and Drug Administration (FDA) and/or European Medicines Agency (EMA)), 10 were based on liposomes, proving the clinical potential of those structures [3]. Gold nanostructures may have not reached such clinical success yet, but the combination of relatively simple, cheap, and well-understood synthesis, beneficial biological half-life, convenient and stable modification due to universal gold–sulfur interactions, and a wide range of activity (photothermal therapy, contrasting agent for photoacoustic imaging, radiosensitization, etc.) make them appear very promising and worth exploring.

2. Targeting Ligands

Ligands of GRPR can fall into one of two groups: agonists and antagonists. Agonists share the receptor activation sequence (Trp-Ala-Val-Gly-His-Leu-Met-NH2) with GRP and activate the GRPR signaling pathways, leading to downstream effects such as cell growth, proliferation, increased motility, and invasiveness. It was pointed out, though, that these effects are not desired in clinically viable formulations. Moreover, some bodies of evidence suggest that antagonists may perform better as targeting ligands [4]. Despite those flaws, surprisingly, most of the research published in the field of nanostrategies for targeting this receptor concerns the use of agonists. One of the possible reasons might be that internalization of the nanoparticle delivering the cargo, together with the receptor upon its activation, may be beneficial for some drug delivery applications and is convenient to track in vitro. However, actual reasons for this state of the matter remain to be elucidated and may be much more trivial, e.g., easy access and broad awareness of bombesin (BBN), the best known GRPR ligand, which happens to be an agonist.
The wide range of agonistic ligands has been shown in the literature. The relatively easiest approach is to use the commercially available native sequence of bombesin [5]. Kulhari and co-workers exploited it in combination with biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles to successfully target both breast and prostate cancer cells and improve docetaxel (DTX) anticancer activity [6][7][8]. The same ligand was also used to target the [64Cu]CuS nanoparticles toward prostate cancer by Cai et al. [9]. Interestingly, using native bombesin, Du, and Li investigated if the synthetic strategy, namely pre/post-functionalization of nanostructured lipid carriers, affects the performance of the nanosystem for targeted lung cancer combination therapy [10].
Variations on the ligand structures start with exchanging single amino acids to engineer the sequence towards facilitated conjugation, for example, replacing the third amino acid from the native sequence with lysin [11][12][13], therefore providing additional -NH2 groups—such ligands are also commercially available [5].
Nevertheless, much more sophisticated structures were also developed. One of the most prominent alterations in the bombesin architecture is to shorten the peptide chain down to an essential receptor binding sequence, Trp-Ala-Val-Gly-His-Leu-Met-NH2, which can lower the price of the custom peptide synthesis. These short peptide chains can also be further engineered to provide convenient means of condensation with nanoparticles [14][15][16], which will be discussed in more detail in the next subchapter. Frequently, the ligand is combined with poly(ethylene glycol) (PEG) to improve the pharmacokinetics of the construct and minimize the reticuloendothelial system uptake upon in vivo administration [17][18].
Adding extra functionality to the structure represents a very attractive strategy for bombesin structure alterations. An example of such modifications is introducing the radioisotope chelation functionality to the ligand. Two main chelators used in such research are 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and hydrazinonicotinic acid (HYNIC), and the isotopes used are 177Lu and 99mTc, respectively [19][20]. Another interesting idea is to combine the bombesin binding motif with another peptide, creating heteromultimeric ligands, which can improve the construct targeting ability (e.g., RGD sequence against integrin αυβ3 [21][22], prostate-specific membrane antigen (PSMA)-inhibiting peptides for targeting of prostate cancer) or cellular penetration (e.g., Tat(49–57), HIV-1-derived sequence [23][24]).
Regarding the antagonistic ligands, GRPR antagonists can be categorized into six classes, out of which, five are peptides/peptoids, while the last class comprises low-molecular flavone derivatives [25]. Classes 2, 3, and 4 (in contrast to classes 1 and 5) are based on the modifications of the binding region of BBN. Class 2 is D-Phe12 analogs; class 3 focuses on modifications in positions 13–14 (or 26–27 when considering GRP sequence), while class 4 comprises analogs devoid of Met14 (desMet14). Among all the papers hereby reviewed, only six deal with the nanosystems exploiting antagonist ligands. Lahooti and colleagues used a class 2 antagonist with D-Phe12 substitution to successfully target their ultrasmall paramagnetic iron oxide nanoparticles (USPION) to GRPR-positive breast cancer xenograft in vivo [26]. Particular attention was given to class 3 antagonist D-Phe-Gln-Trp-Ala-Val- NMeGly-His-Sta-Leu-NH2 (BBN-AA1) by the group of Accardo. They successfully incorporated this sequence into amphiphilic derivative monomer, which was used to form liposomes loaded with doxorubicin (DOX) [27]. The same monomer was also used to form sterically stabilized micelles as a targeted carrier of poorly water-soluble anticancer drug—gold(III) dithiocarbamate [28]. The BBN-AA1 sequence with some spacers and maleimide-reactive cysteine was used to obtain the kit for targeted DOX-loaded liposomes, compliant with Good Manufacturing Practice (GMP), with satisfactory stability [29]. Li and co-workers exploited another class 3 antagonist sequence: [D-Phe6-Sta13-Leu14-NH2]bombesin(6–14) [30]. In their research, this sequence was further modified with Alexa Fluor 750 to obtain a carrier system for molecular imaging of oral squamous cell carcinoma. Tagliviani and co-workers exploited Demobesin-1—a GRPR peptide antagonist that falls into the class 4 analogs [31]. They have shown that, upon adding a trioxatridecan-succinamic acid spacer, Demobesin-1 provided successful cell recognition functionality to the polyoxometalate clusters.
Accardo et al. analyzed the performance of seven different GRPR antagonists based on DOTA and BBN derivatives coupled with PEG—formulations with a very simple design but offering an insight into the mechanisms by which they interact with GRPRs and, hence, provide varying targeting yield and diagnosis options [18]. From their systematic analysis, they concluded that most of the examined BBN derivatives serve equally well for targeting purposes (which was confirmed with gamma camera recordings), but those with NMeGly11 and Sta13-Leu14 would be most suitable for imaging in vivo, since their plasma half-lives are over 15 days, and the latter also provides a favorable absorption mostly into the tumor tissues and no other organs of the body.
As mentioned above, GRPR is the mammalian bombesin receptor family member, comprising three distinct receptors. Basically, each of these receptors is expressed in different neoplastic conditions and has its own set of ligands, however, the universal binding sequence was discovered (D-Tyr6-Gln7-Trp8-Ala9-Val10-βAla11-His12-Phe13-Nle14), sometimes referred to as pan-bombesin. This finding is particularly attractive because with such a ligand it is possible to target tumors expressing various bombesin receptors patterns while improving the construct’s tumor-targeting efficiency and applicability. Heidari and co-workers used a peptide based on a universal binding sequence (Lys-Gly-Gly-Cys-Asp-Phe-Gln-Trp-Ala-Val-bAla-His-Phe-Nle) to target breast cancer in vitro and in vivo with gold nanorods for photothermal therapy [32] as well as imaging [33], and they pointed out its several advantages in comparison to native bombesin sequence, such as overcoming the issues related to receptor heterogeneity in tumors and ameliorating renal clearance due to the negatively charged hydrophilic aspartic acid residue. Similarly, Salouti et al. [34] and Jafari et al. [35] proposed the application of this peptide in breast cancer imaging using gold and superparamagnetic iron oxide nanoparticles, respectively. Pan-bombesin was also shown to improve prostate cancer imaging [36][37].

3. Ligand Incorporation

One of the biggest challenges in the synthesis of particles targeting GRPR or any other receptor is the incorporation of the targeting ligand in the structure of the vehicle. Various approaches can be found in the literature. A state-of-the-art technique based on the formation of an amide linkage between the ligand and the nanoparticle is most commonly used. Chemistry of 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC, EDAC) in combination with N-hydroxysuccinimide (NHS) [13] or sulfo-N-hydroxysuccinimide (sulfo-NHS) [33][38] is most commonly used to create the bond. Usually, this amide is formed between the N-terminus of the peptide ligands and carboxyls on the nanoparticles. Tang and co-workers successfully decorated their poly(acrylic acid)-functionalized lanthanide nanoparticles with BBN analog using EDC/sulfo-NHS chemistry [39]. It was even shown to be feasible to prepare ready-to-use kits with, e.g., stable NHS esters. EDC/NHS reactions are usually led in water, which is beneficial in terms of biocompatibility and purification procedures. However, the reaction, for instance, in tetrahydrofuran (THF) or dimethylformamide (DMF) is also possible, as shown by Du and Li [10] and Mansour et al. [40], respectively.
Nevertheless, with no carboxylic groups available on the surface of the nanoparticle, or no amine group available in the ligand, the other way around can be equally efficient [9][41]. Poly(amidoamine) (PAMAM) dendrimers were conjugated with DOTA-modified BBN using the amine group on the dendrimer and carboxylic group of the DOTA moiety [42][43]. Hajiramezanali and co-workers used this approach to exploit amine groups on chitosan and conjugate succinylated BBN derivative [44]. However, organic solvents and water-insoluble substrates are also used, such as 2-(1H-7-azabenzotriazol-1-yl)-1.1.3.3-tetramethyluroniumhexafluorophosphate) (HATU) [43][45][46] or N,N′-dicyclohexyl carbodiimide (DCC) [31][47] in DMF with the addition of N,N-diisopropylethylamine (DIPEA) [43]. In addition, click chemistry such as thiol-maleimide [29][48][49] or copper-catalyzed azide-alkyne cycloaddition was useful [36][37][50][51]. Dash and colleagues used cysteine groups incorporated in the peptide structure to click the GRPR-binding peptide with maleimide-containing PEGylated magnetic reduced graphene oxide [52].
In some cases, the ligand can be incorporated into the structure of particle-forming substrates before the particle is formed [53]. Accardo et al. have used solid-phase peptide synthesis with Fmoc/tBu chemistry to synthesize the ligand peptide [DOTA-bAla]BBN(7–14) and combine it with the amphiphilic monomers [54]. Subsequently, these monomers were cleaved from the Rink amide resin, purified, and assembled into targeted supramolecular aggregates. A similar approach was adopted by Accardo and co-workers to prepare DOX-loaded targeted liposomes [27]. Kanazawa et al. used this approach to combine bombesin with stearic acid directly in solid-phase peptide synthesis, and they used it for polymeric micelles [55]. Yang and co-workers incorporated the GRPR binding motif of BBN into the structure of their engineered peptides able to form a stable coiled-coil nanostructure [56]. An interesting approach was also presented by Zhang and colleagues—they have genetically engineered Escherichia coli bacteria to express elastin-like peptides capable of coassembly into micelles [57]. One of the peptides was engineered to contain a GRP-derived binding sequence.
In some instances, the application of a linker is necessary due to the configuration of functional groups present in both ligand and particle; both homo- and heterobifunctional linkers are available. For example, Achilli et al. used glutaraldehyde as a homobifunctional amine-reactive crosslinker to functionalize human serum albumin (HSA) protein corona of biohybrid gold nanoparticles with [Lys1-Lys3(DOTA)]BBN [58]. Kim et al. tethered bombesin ligand to amine-modified poly(ethylene glycol) block of amphiphilic copolymer using a heterobifunctional linker, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) [59]. Montet et al. have used amine- and thiol-reactive succinimidyl iodoacetic acid to ligate the BBN derivative with amine-containing iron oxide nanoparticles [60]. Lee and co-workers used N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) to ligate cysteine-terminated derivative with glycol chitosan nanoparticles [61].
In addition, noncovalent bonding may be useful in this context. Successful attachment of the BBN analog to gold nanoparticles can be achieved by exploiting the interaction between nitrogen atoms in free amine groups and the gold surface [12][34]. Ocampo-Garcia et al. have developed a shelf-storage stable kit based on gold nanoparticles operating on this principle [11]. On the other hand, Chanda and co-workers used the thioctic-acid-modified bombesin derivative to exploit thiol–gold interactions for stable functionalization (stable even in a reducing environment of dithiothreitol) [62]. Hosta-Rigau et al. used additional cysteine to provide thiol for interaction with gold [63]. Combining functional linkers such as N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and gold–sulfur interactions can be an interesting alternative for gold nanoparticles [15][61]. Li and colleagues exploited hydrogen bonds and π–π stacking to functionalize nano-graphene oxide with a Sta-BBN ligand [30]. Interestingly, Trujillo-Benítez and co-workers used the DOTA moiety incorporated in the BBN derivative structure to achieve stable chelation of Sm atoms and, therefore, ligation of the ligand with metal oxide nanoparticles [22]. Young et al. have used one of the strongest known noncovalent interaction systems, biotin–streptavidin, to bind biotinylated bombesin to quantum dots decorated with streptavidin, resulting in efficient GRPR-selective fluorescent label operating in vivo [64].
Finally, a ligand can also be protected inside the nanoparticle. De Barros et al. postulate that, due to natural plasma and tissue peptidases, peptides should be protected inside the nanocarrier; therefore, they have encapsulated radiolabeled bombesin derivatives inside the long-circulating pH-sensitive liposomes. This approach led to the successful targeting of GRPR-positive breast cancer and Ehrlich tumor cells [65][66][67].

References

  1. Pooja, D.; Gunukula, A.; Gupta, N.; Adams, D.J.; Kulhari, H. Bombesin receptors as potential targets for anticancer drug delivery and imaging. Int. J. Biochem. Cell Biol. 2019, 114, 105567.
  2. Roser, M.; Ritchie, H. Cancer. Available online: https://ourworldindata.org/cancer (accessed on 14 December 2022).
  3. Anselmo, A.C.; Mitragotri, S. Nanoparticles in the clinic: An update. Bioeng. Transl. Med. 2019, 4, 1–16.
  4. Cescato, R.; Maina, T.; Nock, B.; Nikolopoulou, A.; Charalambidis, D.; Piccand, V.; Reubi, J.C. Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J. Nucl. Med. 2008, 49, 318–326.
  5. Podstawka, E. Investigation of molecular structure of bombesin and its modified analogues nonadsorbed and adsorbed on electrochemically roughened silver surface. Biopolymers 2008, 89, 506–521.
  6. Kulhari, H.; Kulhari, D.P.; Singh, M.K.; Sistla, R. Colloidal stability and physicochemical characterization of bombesin conjugated biodegradable nanoparticles. Colloids Surf. A Physicochem. Eng. Asp. 2014, 443, 459–466.
  7. Kulhari, H.; Pooja, D.; Shrivastava, S.; Naidu, V.G.M.; Sistla, R. Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel. Colloids Surf. B Biointerfaces 2014, 117, 166–173.
  8. Radhakrishnan, R.; Pooja, D.; Kulhari, H.; Gudem, S.; Ravuri, H.G.; Bhargava, S.; Ramakrishna, S. Bombesin conjugated solid lipid nanoparticles for improved delivery of epigallocatechin gallate for breast cancer treatment. Chem. Phys. Lipids 2019, 224, 104770.
  9. Cai, H.; Xie, F.; Mulgaonkar, A.; Chen, L.; Sun, X.; Hsieh, J.T.; Peng, F.; Tian, R.; Li, L.; Wu, C.; et al. Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer. Nanomedicine 2018, 13, 1695–1705.
  10. Du, J.; Li, L. Which one performs better for targeted lung cancer combination therapy: Pre- or post-bombesin-decorated nanostructured lipid carriers? Drug Deliv. 2016, 23, 1799–1809.
  11. Ocampo-García, B.; Ferro-Flores, G.; Morales-Avila, E.; Ramírez, F.D.M. Kit for preparation of multimeric receptor-specific 99mTc-radiopharmaceuticals based on gold nanoparticles. Nucl. Med. Commun. 2011, 32, 1095–1104.
  12. Mendoza-Sánchez, A.N.; Ferro-Flores, G.; Ocampo-García, B.E.; Morales-Avila, E.; Ramírez, F.D.M.; De León-Rodríguez, L.M.; Santos-Cuevas, C.L.; Medina, L.A.; Rojas-Calderón, E.L.; Camacho-López, M.A. Lys3-bombesin conjugated to 99mTc-labelled gold nanoparticles for in vivo gastrin releasing peptide-receptor imaging. J. Biomed. Nanotechnol. 2010, 6, 375–384.
  13. Bleul, R.; Thiermann, R.; Marten, G.U.; House, M.J.; Pierre, T.G.S.; Häfeli, U.O.; Maskos, M. Continuously manufactured magnetic polymersomes—A versatile tool (not only) for targeted cancer therapy. Nanoscale 2013, 5, 11385–11393.
  14. Suresh, D.; Zambre, A.; Chanda, N.; Hoffman, T.J.; Smith, C.J.; Robertson, J.D.; Kannan, R. Bombesin peptide conjugated gold nanocages internalize via clathrin mediated endocytosis. Bioconjug. Chem. 2014, 25, 1565–1579.
  15. Silva, F.; Paulo, A.; Pallier, A.; Même, S.; Tóth, É.; Gano, L.; Marques, F.; Geraldes, C.F.G.C.; Castro, M.M.C.A.; Cardoso, A.M.; et al. Dual imaging gold nanoplatforms for targeted radiotheranostics. Materials 2020, 13, 513.
  16. Silva, F.; Gano, L.; Cabral Campello, M.P.; Marques, R.; Prudêncio, I.; Zambre, A.; Upendran, A.; Paulo, A.; Kannan, R. In vitro / in vivo “peeling” of multilayered aminocarboxylate gold nanoparticles evidenced by a kinetically stable 99mTc-label. Dalt. Trans. 2017, 46, 14572–14583.
  17. Chilug, L.E.; Niculae, D.; Leonte, R.A.; Nan, A.; Turcu, R.; Mustaciosu, C.; Serban, R.M.; Lavric, V.; Manda, G. Preclinical evaluation of NHS-activated gold nanoparticles functionalized with bombesin or neurotensin-like peptides for targeting colon and prostate tumours. Molecules 2020, 25, 3363.
  18. Accardo, A.; Galli, F.; Mansi, R.; Del Pozzo, L.; Aurilio, M.; Morisco, A.; Ringhieri, P.; Signore, A.; Morelli, G.; Aloj, L. Pre-clinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors. EJNMMI Res. 2016, 6, 1–10.
  19. Matusiak, M.; Rurarz, B.P.; Kadłubowski, S.; Wolszczak, M.; Karczmarczyk, U.; Maurin, M.; Kolesińska, B.; Ulański, P. Synthesis and properties of targeted radioisotope carriers based on poly(acrylic acid) nanogels. Pharmaceutics 2021, 13, 1240.
  20. Santos-Cuevas, C.L.; Ferro-Flores, G.; Arteaga de Murphy, C.; Ramírez, F.d.M.; Luna-Gutiérrez, M.A.; Pedraza-López, M.; García-Becerra, R.; Ordaz-Rosado, D. Design, preparation, in vitro and in vivo evaluation of 99mTc-N2S2-Tat(49-57)-bombesin: A target-specific hybrid radiopharmaceutical. Int. J. Pharm. 2009, 375, 75–83.
  21. Hu, K.; Wang, H.; Tang, G.; Huang, T.; Tang, X.; Liang, X.; Yao, S.; Nie, D. In vivo cancer dual-targeting and dual-modality imaging with functionalized quantum dots. J. Nucl. Med. 2015, 56, 1278–1284.
  22. Trujillo-Benítez, D.; Ferro-Flores, G.; Morales-Avila, E.; Jiménez-Mancilla, N.; Ancira-Cortez, A.; Ocampo-García, B.; Santos-Cuevas, C.; Escudero-Castellanos, A.; Luna-Gutiérrez, M.; Azorín-Vega, E. Synthesis and biochemical evaluation of samarium-153 oxide nanoparticles functionalized with iPSMA-bombesin heterodimeric peptide. J. Biomed. Nanotechnol. 2020, 16, 689–701.
  23. Jimenez-Mancilla, N.; Ferro-Flores, G.; Ocampo-Garcia, B.; Luna-Gutierrez, M.; De Maria Ramirez, F.; Pedraza-Lopez, M.; Torres-Garcia, E. Multifunctional targeted radiotherapy system for induced tumours expressing gastrin-releasing peptide receptors. Curr. Nanosci. 2012, 8, 193–201.
  24. Jiménez-Mancilla, N.; Ferro-Flores, G.; Santos-Cuevas, C.; Ocampo-García, B.; Luna-Gutiérrez, M.; Azorín-Vega, E.; Isaac-Olivé, K.; Camacho-López, M.; Torres-García, E. Multifunctional targeted therapy system based on 99mTc/ 177Lu-labeled gold nanoparticles-Tat(49-57)-Lys3-bombesin internalized in nuclei of prostate cancer cells. J. Label. Compd. Radiopharm. 2013, 56, 663–671.
  25. Jensen, R.T.; Battey, J.F.; Spindel, E.R.; Benya, R.V. International union of pharmacology. LXVIII. Mammalian bombesin receptors: Nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol. Rev. 2008, 60, 1–42.
  26. Lahooti, A.; Shanehsazzadeh, S.; Laurent, S. Preliminary studies of 68Ga-NODA-USPION-BBN as a dual-modality contrast agent for use in positron emission tomography/magnetic resonance imaging. Nanotechnology 2020, 31, 015102.
  27. Accardo, A.; Mansi, R.; Salzano, G.; Morisco, A.; Aurilio, M.; Parisi, A.; Maione, F.; Cicala, C.; Ziaco, B.; Tesauro, D.; et al. Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells. J. Drug Target. 2013, 21, 240–249.
  28. Ringhieri, P.; Iannitti, R.; Nardon, C.; Palumbo, R.; Fregona, D.; Morelli, G.; Accardo, A. Target selective micelles for bombesin receptors incorporating Au(III)-dithiocarbamato complexes. Int. J. Pharm. 2014, 473, 194–202.
  29. Accardo, A.; Mannucci, S.; Nicolato, E.; Vurro, F.; Diaferia, C.; Bontempi, P.; Marzola, P.; Morelli, G. Easy formulation of liposomal doxorubicin modified with a bombesin peptide analogue for selective targeting of GRP receptors overexpressed by cancer cells. Drug Deliv. Transl. Res. 2019, 9, 215–226.
  30. Li, R.; Gao, R.; Wang, Y.; Liu, Z.; Xu, H.; Duan, A.; Zhang, F.; Ma, L. Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma. Sci. Rep. 2020, 10, 1–12.
  31. Tagliavini, V.; Honisch, C.; Serratì, S.; Azzariti, A.; Bonchio, M.; Ruzza, P.; Carraro, M. Enhancing the biological activity of polyoxometalate-peptide nano-fibrils by spacer design. RSC Adv. 2021, 11, 4952–4957.
  32. Coenen, H.H.; Gee, A.D.; Adam, M.; Antoni, G.; Cutler, C.S.; Fujibayashi, Y.; Jeong, J.M.; Mach, R.H.; Mindt, T.L.; Pike, V.W.; et al. Open letter to journal editors on: International consensus radiochemistry nomenclature guidelines. J. Labelled Comp. Radiopharm. 2018, 61, 402–404.
  33. Heidari, Z.; Sariri, R.; Salouti, M. Gold nanorods-bombesin conjugate as a potential targeted imaging agent for detection of breast cancer. J. Photochem. Photobiol. B Biol. 2014, 130, 40–46.
  34. Salouti, M.; Saghatchi, F. BBN conjugated GNPs: A new targeting contrast agent for imaging of breast cancer in radiology. IET Nanobiotechnology 2017, 11, 604–611.
  35. Jafari, A.; Salouti, M.; Shayesteh, S.F.; Heidari, Z.; Rajabi, A.B.; Boustani, K.; Nahardani, A. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI. Nanotechnology 2015, 26, 075101.
  36. Martin, A.L.; Hickey, J.L.; Ablack, A.L.; Lewis, J.D.; Luyt, L.G.; Gillies, E.R. Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells. J. Nanoparticle Res. 2010, 12, 1599–1608.
  37. Steinmetz, N.F.; Ablack, A.L.; Hickey, J.L.; Ablack, J.; Manocha, B.; Mymryk, J.S.; Luyt, L.G.; Lewis, J.D. Intravital imaging of human prostate cancer using viral nanoparticles targeted to gastrin-releasing peptide receptors. Small 2011, 7, 1664–1672.
  38. Heidari, Z.; Salouti, M.; Sariri, R. Breast cancer photothermal therapy based on gold nanorods targeted by covalently-coupled bombesin peptide. Nanotechnology 2015, 26, 195101.
  39. Tang, S.H.; Wang, J.; Yang, C.X.; Dong, L.X.; Kong, D.; Yan, X.P. Ultrasonic assisted preparation of lanthanide-oleate complexes for the synthesis of multifunctional monodisperse upconversion nanoparticles for multimodal imaging. Nanoscale 2014, 6, 8037–8044.
  40. Mansour, N.; Paquette, M.; Ait-Mohand, S.; Dumulon-Perreault, V.; Guérin, B. Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: -DOTHA2-PEG-RM26. Nucl. Med. Biol. 2018, 56, 31–38.
  41. Tangthong, T.; Piroonpan, T.; Thipe, V.C.; Khoobchandani, M.; Katti, K.; Katti, K.V.; Pasanphan, W. Bombesin peptide conjugated water-soluble chitosan gallate—A new nanopharmaceutical architecture for the rapid one-pot synthesis of prostate tumor targeted gold nanoparticles. Int. J. Nanomed. 2021, 16, 6957–6981.
  42. Mendoza-Nava, H.; Ferro-Flores, G.; Ramírez, F.D.M.; Ocampo-García, B.; Santos-Cuevas, C.; Aranda-Lara, L.; Azorín-Vega, E.; Morales-Avila, E.; Isaac-Olivé, K. 177Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity: A potential theranostic radiopharmaceutical. J. Nanomater. 2016, 2016, 1039258.
  43. Wang, Z.; Ye, M.; Ma, D.; Shen, J.; Fang, F. Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer. J. Biomater. Sci. Polym. Ed. 2022, 33, 197–211.
  44. Hajiramezanali, M.; Atyabi, F.; Mosayebnia, M.; Akhlaghi, M.; Geramifar, P.; Jalilian, A.R.; Mazidi, S.M.; Yousefnia, H.; Shahhosseini, S.; Beiki, D. (68)Ga-radiolabeled bombesin-conjugated to trimethyl chitosan-coated superparamagnetic nanoparticles for molecular imaging: Preparation, characterization and biological evaluation. Int. J. Nanomed. 2019, 14, 2591–2605.
  45. Mendoza-Nava, H.; Ferro-Flores, G.; Ramírez, F.d.M.; Ocampo-García, B.; Santos-Cuevas, C.; Azorín-Vega, E.; Jiménez-Mancilla, N.; Luna-Gutiérrez, M.; Isaac-Olivé, K. Fluorescent, plasmonic, and radiotherapeutic properties of the 177Lu–dendrimer-AuNP–folate–bombesin nanoprobe located inside cancer cells. Mol. Imaging 2017, 16, 153601211770476.
  46. Gibbens-Bandala, B.; Morales-Avila, E.; Ferro-Flores, G.; Santos-Cuevas, C.; Meléndez-Alafort, L.; Trujillo-Nolasco, M.; Ocampo-García, B. 177Lu-Bombesin-PLGA (paclitaxel): A targeted controlled-release nanomedicine for bimodal therapy of breast cancer. Mater. Sci. Eng. C 2019, 105, 110043.
  47. Gibbens-Bandala, B.; Morales-Avila, E.; Ferro-Flores, G.; Santos-Cuevas, C.; Luna-Gutiérrez, M.; Ramírez-Nava, G.; Ocampo-García, B. Synthesis and evaluation of 177Lu-DOTA-DN(PTX)-BN for selective and concomitant radio and drug-therapeutic effect on breast cancer cells. Polymers 2019, 11, 1572.
  48. Wang, X.L.; Xu, R.; Wu, X.; Gillespie, D.; Jensen, R.; Lu, Z.R. Targeted systemic delivery of a therapeutic siRNA with a multifunctional carrier controls tumor proliferation in mice. Mol. Pharm. 2009, 6, 738–746.
  49. Akbar, M.J.; Ferreira, P.C.L.; Giorgetti, M.; Stokes, L.; Morris, C.J. Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells. Beilstein J. Nanotechnol. 2019, 10, 2553–2562.
  50. Li, L.; Wu, C.; Pan, L.; Li, X.; Kuang, A.; Cai, H.; Tian, R. Bombesin-functionalized superparamagnetic iron oxide nanoparticles for dual-modality MR/NIRFI in mouse models of breast cancer. Int. J. Nanomed. 2019, 14, 6721–6732.
  51. Hussein, W.M.; Cheong, Y.S.; Liu, C.; Liu, G.; Begum, A.A.; Attallah, M.A.; Moyle, P.M.; Torchilin, V.P.; Smith, R.; Toth, I. Peptide-based targeted polymeric nanoparticles for siRNA delivery. Nanotechnology 2019, 30, 415604.
  52. Dash, B.S.; Lu, Y.-J.; Chen, H.-A.; Chuang, C.-C.; Chen, J.-P. Magnetic and GRPR-targeted reduced graphene oxide/doxorubicin nanocomposite for dual-targeted chemo-photothermal cancer therapy. Mater. Sci. Eng. C 2021, 128, 112311.
  53. Wang, C.; Sun, X.; Wang, K.; Wang, Y.; Yang, F.; Wang, H. Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers. Drug Deliv. 2016, 23, 2697–2702.
  54. Accardo, A.; Mansi, R.; Morisco, A.; Mangiapia, G.; Paduano, L.; Tesauro, D.; Radulescu, A.; Aurilio, M.; Aloj, L.; Arra, C.; et al. Peptide modified nanocarriers for selective targeting of bombesin receptors. Mol. Biosyst. 2010, 6, 878–887.
  55. Kanazawa, T.; Taki, H.; Okada, H. Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas. Eur. J. Pharm. Biopharm. 2020, 152, 85–94.
  56. Yang, Y.; Neef, T.; Mittelholzer, C.; Garcia Garayoa, E.; Bläuenstein, P.; Schibli, R.; Aebi, U.; Burkhard, P. The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms. J. Nanobiotechnology 2013, 11, 1–10.
  57. Zhang, W.; Garg, S.; Eldi, P.; Zhou, F.H.; Johnson, I.R.D.; Brooks, D.A.; Lam, F.; Rychkov, G.; Hayball, J.; Albrecht, H. Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide. Int. J. Pharm. 2016, 513, 270–279.
  58. Achilli, E.; Flores, C.Y.; Temprana, C.F.; Alonso, S.d.V.; Radrizzani, M.; Grasselli, M. Enhanced gold nanoparticle-tumor cell recognition by albumin multilayer coating. OpenNano 2022, 6, 100033.
  59. Kim, J.; Kim, J.S.; Min, K.H.; Kim, Y.-H.; Chen, X.; Kim, J.; Kim, J.S.; Min, K.H.; Kim, Y.-H.; Chen, X. Bombesin-tethered reactive oxygen species (ROS)-responsive nanoparticles for monomethyl auristatin F (MMAF) delivery. Bioeng. 2021, 8, 43.
  60. Montet, X.; Weissleder, R.; Josephson, L. Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas. Bioconjug. Chem. 2006, 17, 905–911.
  61. Lee, C.M.; Jeong, H.J.; Cheong, S.J.; Kim, E.M.; Kim, D.W.; Lim, S.T.; Sohn, M.H. Prostate cancer-targeted imaging using magnetofluorescent polymeric nanoparticles functionalized with bombesin. Pharm. Res. 2010, 27, 712–721.
  62. Chanda, N.; Kattumuri, V.; Shukla, R.; Zambre, A.; Katti, K.; Upendran, A.; Kulkarni, R.R.; Kan, P.; Fent, G.M.; Casteel, S.W.; et al. Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proc. Natl. Acad. Sci. USA 2010, 107, 8760–8765.
  63. Hosta-Rigau, L.; Olmedo, I.; Arbiol, J.; Cruz, L.J.; Kogan, M.J.; Albericio, F. Multifunctionalized gold nanoparticles with peptides targeted to gastrin-releasing peptide receptor of a tumor cell line. Bioconjug. Chem. 2010, 21, 1070–1078.
  64. Young, S.H.; Rozengurt, E. Qdot Nanocrystal Conjugates conjugated to bombesin or ANG II label the cognate G protein-coupled receptor in living cells. Am. J. Physiol.—Cell Physiol. 2006, 290, 728–732.
  65. De Barros, A.L.B.; Mota, L.D.G.; Soares, D.C.F.; Coelho, M.M.A.; Oliveira, M.C.; Cardoso, V.N. Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification. Bioorg. Med. Chem. Lett. 2011, 21, 7373–7375.
  66. De Barros, A.L.B.; Mota, L.D.G.; Soares, D.C.F.; De Souza, C.M.; Cassali, G.D.; Oliveira, M.C.; Cardoso, V.N. Long-circulating, pH-sensitive liposomes versus long-circulating, non-pH-sensitive liposomes as a delivery system for tumor identification. J. Biomed. Nanotechnol. 2013, 9, 1636–1643.
  67. De Barros, A.L.B.; Das Graças Mota, L.; Coelho, M.M.A.; Corrêa, N.C.R.; De Góes, A.M.; Oliveira, M.C.; Cardoso, V.N. Bombesin encapsulated in long-circulating pH-sensitive liposomes as a radiotracer for breast tumor identification. J. Biomed. Nanotechnol. 2015, 11, 342–350.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Nanoscience & Nanotechnology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Beata Paulina Rurarz
,
Małgorzata Bukowczyk
,
Natalia Gibka
,
Agnieszka Wanda Piastowska-Ciesielska
,
Urszula Karczmarczyk
,
Piotr Ulański
View Times: 466
Revisions: 2 times (View History)
Update Date: 27 Feb 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback