Leukaemia is the most prevalent form of cancer-causing death in a large number of populations and needs prompt and effective treatment. Chemotherapeutics can be used to treat leukaemia, but their pronounced killing effects to other living cells is still an issue. Active targeting to certain specific receptors in leukaemic cells is the best way to avoid damage to other living cells. Leukaemic cells can be targeted using novel nanoparticles (NPs) coated with a specific ligand, such as octreotide (OCD), to target somatostatin receptor type 2 (SSTR2), which is expressed in leukaemic cells.
Amino-PEGylated quantum dots (QDs) were chosen as model NPs. The QDs were first succinylated using succinic anhydride and then coated with OCD. The reactivity and selectivity of the formulated QDs-OCD were studied in cell lines with well-expressed SSTR2, while fluorescence was detected using confocal laser scanning microscopy (CLSM) and flow cytometry (FACS). Conclusively, QD-OCD targeting to blood cells was studied in vivo in mice and detected using inductively coupled plasma mass spectrometry and CLSM in tissues.
Highly stable QDs coated with OCD were prepared. FACS and CLSM showed highly definite interactions with overexpressed SSTR2 in the investigated cell lines. Moreover, the in vivo results revealed a higher concentration of QDs-OCD in blood cells. The fluorescence intensity of the QDs-OCD was highly accumulated in blood cells, while the unmodified QDs did not accumulate significantly in blood cells. Conclusion: The formulated novel QDs-OCD can target SSTR2 overexpressed in blood cells with great potential for treating blood cancer.
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Abdellatif A. Octreotide labelled fluorescein isothiocyanate for identification of somatostatin receptor subtype 2. Biochem Physiol. 2015;4(183):2.
Abdellatif AAH. A plausible way for excretion of metal nanoparticles active targeting. Drug Dev Ind Pharm. 2020;46(5):744–50.
Abdellatif, A.A.H., Tawfeek, H.M. Transfersomal Nanoparticles for Enhanced Transdermal Delivery of Clindamycin. AAPS PharmSciTech. 2016;17:1067–74.https://doi.org/10.1208/s12249-015-0441-7.
Abdellatif AA, Zaki AM, Abdo HM, Aly DG, Emara TA, El-Toukhy S, et al. Assessment of serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) among non-segmental vitiligo patients: a pilot study. Acta Dermatovenerol Alp Pannonica Adriat. 2015;24(3):43–5.
Abdellatif AA, Zayed G, El-Bakry A, Zaky A, Saleem IY, Tawfeek HM. Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors. Drug Dev Ind Pharm. 2016;42(11):1782–91.
Abdellatif AA, Tawfeek H. Development and evaluation of fluorescent gold nanoparticles. Drug Dev Ind Pharm. 2019;44(10):1679–716.
Abdellatif AAH, Abou-Taleb HA, Abd El Ghany AA, Lutz I, Bouazzaoui A. Targeting of somatostatin receptors expressed in blood cells using quantum dots coated with vapreotide. Saudi Pharm J. 2018;26(8):1162–9.
Abdellatif AAH, Aldalaen SM, Faisal W, Tawfeek HM. Somatostatin receptors as a new active targeting sites for nanoparticles. Saudi Pharm J. 2018;26(7):1051–9.
Ahmed A. H. Abdellatif. Identification of somatostatin receptors using labeled PEGylated octreotide, as an active internalization, Drug Dev Ind Pharm. 2019:45(10):1707–15. https://doi.org/10.1080/03639045.2019.1656735.
Abdellatif AAH, Abdelhafez WA, Sarhan HA. Somatostatin decorated quantum dots nanoparticles for targeting of somatostatin receptors %. J Iran J Pharm Res. 2018;17(2):513–24.
Xu T, Zhang Q, Fan YH, Li RQ, Lu H, Zhao SM, Jiang TL. Quantitative and multiplexed detection for blood typing based on quantum dot–magnetic bead assay. Int J Nanomedicine. 2017;12:3347–56. https://doi.org/10.2147/IJN.S133247.
Badia A, Cuccia L, Demers L, Morin F, Lennox RB. Structure and dynamics in alkanethiolate monolayers self-assembled on gold nanoparticles: a DSC, FT-IR, and deuterium NMR study. J Am Chem Soc. 1997;119(11):2682–92.
Bertrand N, Leroux JC. The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Release. 2012;161(2):152–63.
Bhathena SJ, Recant L. Somatostatin receptors on circulating human blood cells. Horm Metab Res. 1980;12(6):277–8.
Bhunchu S, Rojsitthisak P. Biopolymeric alginate-chitosan nanoparticles as drug delivery carriers for cancer therapy. Pharmazie. 2014;69(8):563–70.
Botha MC, Jones M, de Klerk WA, Yamamoto N. Distribution and possible spread of human T-cell leukaemia virus type I in human communities in the northern and eastern Transvaal. S Afr Med J. 1985;67(17):668–71.
Cai W, Chen X. Preparation of peptide-conjugated quantum dots for tumor vasculature-targeted imaging. Nat Protoc. 2008;3(1):89–96.
Cantarella CD, Ragusa D, Giammanco M, Tosi S. Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature. Genes Nutr. 2017;12:14.
Chavez-Gonzalez A, Bakhshinejad B, Pakravan K, Guzman ML, Babashah S. Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer. Cell Oncol (Dordr). 2017;40(1):1–20.
Dassenoy F, Philippot K, Ould-Ely T, Amiens C, Lecante P, Snoeck E, et al. Platinum nanoparticles stabilized by CO and octanethiol ligands or polymers: FT-IR, NMR, HREM and WAXS studies. New J Chem. 1998;22(7):703–11.
Demaree CJ, Soliz JM, Gebhardt R. Cancer seeding risk from an epidural blood patch in patients with leukemia or lymphoma. Pain Med. 2017;18(4):786–90.
Abdellatif, A.A.H., Ibrahim, M.A., Amin, M.A. et al. Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors. Sci Rep. 2020;10:4736.https://doi.org/10.1038/s41598-020-61605-y.
Diaz-Visurraga J, Daza C, Pozo C, Becerra A, von Plessing C, Garcia A. Study on antibacterial alginate-stabilized copper nanoparticles by FT-IR and 2D-IR correlation spectroscopy. Int J Nanomedicine. 2012;7:3597–612.
Edrees BM, Athar M, Abduljaleel Z, Al-Allaf FA, Taher MM, Khan W, et al. Functional alterations due to amino acid changes and evolutionary comparative analysis of ARPKD and ADPKD genes. Genom Data. 2016;10:127–34.
Greaves M. Leukaemia ‘firsts’ in cancer research and treatment. Nat Rev Cancer. 2016;16(3):163–72.
Greenwood R, Kendall K. Selection of suitable dispersants for aqueous suspensions of zirconia and titania powders using acoustophoresis. J Eur Ceram Soc. 1999;19(4):479–88.
Hennig R, Pollinger K, Tessmar J, Goepferich A. Multivalent targeting of AT1receptors with angiotensin II-functionalized nanoparticles. J Drug Target. 2015;23(7–8):681–9.
Hiruma K, Koike T, Nakamura H, Sumida T, Maeda T, Tomioka H, Yoshida S, Fujita T. Somatostatin receptors on human lymphocytes and leukaemia cells. Immunology. 1990;71(4):480–5.
Hohla F, Buchholz S, Schally AV, Krishan A, Rick FG, Szalontay L, Papadia A, Halmos G, Koster F, Aigner E, Datz C, Seitz S. Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells. Cancer Lett. 2010;294(1):35–42.
Huang H, Wang D, Zhang Y, Zhou Y, Geng J, Chitgupi U, Cook TR, Xia J, Lovell JF. Axial PEGylation of tin octabutoxy naphthalocyanine extends blood circulation for photoacoustic vascular imaging. Bioconjug Chem. 2016;27(7):1574–8.
Ishihara S, Hassan S, Kinoshita Y, Moriyama N, Fukuda R, Maekawa T, Okada A, Chiba T. Growth inhibitory effects of somatostatin on human leukemia cell lines mediated by somatostatin receptor subtype 1. Peptides. 1999;20(3):313–8.
Juarez R, Parker SF, Concepcion P, Corma A, Garcia H. Heterolytic and heterotopic dissociation of hydrogen on ceria-supported gold nanoparticles. Combined inelastic neutron scattering and FT-IR spectroscopic study on the nature and reactivity of surface hydrogen species. Chem Sci. 2010;1(6):731–8.
Kanakis G, Grimelius L, Spathis A, Tringidou R, Rassidakis GZ, Oberg K, et al. Expression of somatostatin receptors 1-5 and dopamine receptor 2 in lung carcinoids: implications for a therapeutic role. Neuroendocrinology. 2015;101(3):211–22.
Kane PF, Hall WL Jr. Determination of arsenic, cadmium, cobalt, chromium, lead, molybdenum, nickel, and selenium in fertilizers by microwave digestion and inductively coupled plasma-optical emission spectrometry detection: collaborative study. J AOAC Int. 2006;89(6):1447–66.
Kidwai SA, Ansari AA, Salahuddin A. Effect of succinylation (3-Carboxypropionylation) on conformation and immunological activity of ovalbumin. Biochem J. 1976;155(1):171–80.
Kinstler OB, Brems DN, Lauren SL, Paige AG, Hamburger JB, Treuheit MJ. Characterization and stability of N-terminally PEGylated rhG-CSF. Pharm Res. 1996;13(7):996–1002.
Kumar AH, Clover AJ. Intraperitoneal co-administration of low dose urethane with xylazine and ketamine for extended duration of surgical anesthesia in rats. Lab Anim Res. 2015;31(4):174–9.
Lapa C, Hanscheid H, Wild V, Pelzer T, Schirbel A, Werner RA, et al. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy. Oncotarget. 2016;7(15):20033–40.
Lichtenauer-Kaligis EG, Dalm VA, Oomen SP, Mooij DM, van Hagen PM, Lamberts SW, Hofland LJ. Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets. Eur J Endocrinol. 2004;150(4):565–77.
Merrell. Octreotide scintigraphy. A new method for diagnosing pancreatic tumors. Ann Surg. 1996;224(2):117–8.
Monti G, Schrijver R, Beier D. Genetic diversity and spread of bovine leukaemia virus isolates in argentine dairy cattle. Arch Virol. 2005;150(3):443–58.
Muscarella LA, D'Alessandro V, la Torre A, Copetti M, De Cata A, Parrella P, et al. Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients. Cell Oncol (Dordr). 2011;34(5):435–41.
Na DH, Murty SB, Lee KC, Thanoo BC, DeLuca PP. Preparation and stability of poly(ethylene glycol) (PEG)ylated octreotide for application to microsphere delivery. AAPS PharmSciTech. 2003;4(4):E72.
Oomen SP, Lichtenauer-Kaligis EG, Verplanke N, Hofland J, Lamberts SW, Lowenberg B, et al. Somatostatin induces migration of acute myeloid leukemia cells via activation of somatostatin receptor subtype 2. Leukemia. 2001;15(4):621–7.
Ostolska I, Wisniewska M. Application of the zeta potential measurements to explanation of colloidal Cr2O3 stability mechanism in the presence of the ionic polyamino acids. Colloid Polym Sci. 2014;292(10):2453–64.
Parekh D, Ishizuka J, Townsend CM Jr, Haber B, Beauchamp RD, Karp G, Kim SW, Rajaraman S, Greeley G Jr, Thompson JC. Characterization of a human pancreatic carcinoid in vitro: morphology, amine and peptide storage, and secretion. Pancreas. 1994;9(1):83–90.
Perez J, Viollet C, Doublier S, Videau C, Epelbaum J, Baud L. Somatostatin binds to murine macrophages through two distinct subsets of receptors. J Neuroimmunol. 2003;138(1–2):38–44.
Petrak K. Essential properties of drug-targeting delivery systems. Drug Discov Today. 2005;10(23–24):1667–73.
Pollinger K, Hennig R, Breunig M, Tessmar J, Ohlmann A, Tamm ER, Witzgall R, Goepferich A. Kidney podocytes as specific targets for cyclo(RGDfC)-modified nanoparticles. Small. 2012;8(21):3368–75.
Pollinger K, Hennig R, Ohlmann A, Fuchshofer R, Wenzel R, Breunig M, Tessmar J, Tamm ER, Goepferich A. Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application. Proc Natl Acad Sci U S A. 2013;110:6115–20.
Prakash H, Mazumdar S. Succinylation of cytochrome c investigated by electrospray ionization mass spectrometry: reactive lysine residues. Int J Mass Spectrom. 2009;281(1–2):55–62.
Reynaert H, van Rossen E, Uyama N, Chatterjee N, Kumar U, Urbain D, et al. Expression of somatostatin receptors in splanchnic blood vessels of normal and cirrhotic rats. Liver Int. 2007;27(6):825–31.
Simsek S, Eroglu H, Kurum B, Ulubayram K. Brain targeting of atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles. J Microencapsul. 2013;30(1):10–20.
Tawfeek HM, Abdellatif AAH, Dennison TJ, Mohammed AR, Sadiq Y, Saleem IY. Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets. Int J Pharm. 2017;531(1):80–9.
Thakur D, Jain A, Ghoshal G, Shivhare US, Katare OP. Microencapsulation of beta-carotene based on casein/guar gum blend using zeta potential-yield stress phenomenon: an approach to enhance photo-stability and retention of functionality. AAPS PharmSciTech. 2017;18(5):1447–59.
Todisco M. Chronic lymphocytic leukemia: long-lasting remission with combination of cyclophosphamide, somatostatin, bromocriptine, retinoids, melatonin, and ACTH. Cancer Biother Radiopharm. 2009;24(3):353–5.
Updegrove TB, Correia JJ, Chen Y, Terry C, Wartell RM. The stoichiometry of the Escherichia coli Hfq protein bound to RNA. RNA. 2011;17(3):489–500.
Vannucci L, Falvo E, Fornara M, Di Micco P, Benada O, Krizan J, et al. Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles. Int J Nanomedicine. 2012;7:1489–509.
ter Veld F, Herder C, Mussmann R, Martin S, Kempf K. Somatostatin receptor expression in peripheral blood of type 2 diabetes mellitus patients. Horm Metab Res. 2007;39(3):230–2.
Wang YF, Shi YZ, Zhang H, Chen YH, Lau J, Wilbur S, et al. Determination of lead, cadmium, mercury, chromium and arsenic in acrylonitrile-butadiene-styrene copolymer using microwave digestion-ICP-MS. Guang Pu Xue Yu Guang Pu Fen Xi. 2008;28(1):191–4.
Xin H, Sha X, Jiang X, Zhang W, Chen L, Fang X. Anti-glioblastoma efficacy and safety of paclitaxel-loading angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials. 2012;33(32):8167–76.
Zahr AS, Davis CA, Pishko MV. Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol). Langmuir. 2006;22(19):8178–85.
Acknowledgments and Disclosures
The researchers would like to thank the Deanship of Scientific Research, Qassim University, for support of this project. The authors declare no conflicts of interest.
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Abdellatif, A.A.H., Hennig, R., Pollinger, K. et al. Fluorescent Nanoparticles Coated with a Somatostatin Analogue Target Blood Monocyte for Efficient Leukaemia Treatment. Pharm Res 37, 217 (2020). https://doi.org/10.1007/s11095-020-02938-1
- fluorescent nanoparticles, leukaemia, active targeting
- PEGylated quantum dots
- somatostatin receptors