We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Research Article

Peptide-functionalized nanoparticles for the selective induction of apoptosis in target cells

    Nicole Remaliah S Sibuyi

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Ntevheleni Thovhogi

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Kwazikwakhe B Gabuza

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Miche D Meyer

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Mustafa Drah

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Martin O Onani

    Organometallics & Nanomaterials, Department of Chemistry, UWC, Private Bag X17, Bellville, 7535, Western Cape, South Africa

    ,
    Amanda Skepu

    DST/Mintek NIC, Biolabels Unit, Advanced Materials Division, Mintek, Private Bag X3015, Randburg, 2125, Gauteng, South Africa

    ,
    Abram M Madiehe

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    &
    Mervin Meyer

    *Author for correspondence:

    E-mail Address: memeyer@uwc.ac.za

    DST/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Unit, Department of Biotechnology, University of the Western Cape (UWC), Private Bag X17, Bellville, 7535, Western Cape, South Africa

    Published Online:https://doi.org/10.2217/nnm-2017-0085

    Aim: The study developed a prohibitin (PHB) targeted nanotherapy for selective induction of apoptosis in target cells. Methods: Gold nanoparticles (AuNPs) were bifunctionalized with adipose homing and proapoptotic peptides. The efficacy and mode of cell death induced by the AuNPs were investigated in vitro on three cancer cell lines. Results: The antiproliferative activity of PHB-targeted bifunctionalized AuNPs was more pronounced on cells that express the PHB receptor, and demonstrated receptor-mediated targeting and selectivity. The bifunctionalized AuNPs induced cell death by apoptosis. Conclusion: The PHB-targeted nanotherapy under study could potentially be used for treatment of diseases that are characterized by overexpression of PHB. As such, further investigations will be conducted in vivo.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Baldo BA, Pham NH. Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch. Cancer Metastasis Rev. 32(3–4), 723–761 (2013).
    • 2 Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur. J. Pharm. Biopharm. 93, 52–79 (2015).
    • 3 Lu DY, Lu TR, Che JY, Wu HY. Individualized cancer therapy. Innovations Pharm. Pharmacother. 2(4), 458–469 (2014).
    • 4 Haslam D. Weight management in obesity – past and present. Int. J. Clin. Pract. 70(3), 206–217 (2016).
    • 5 Bray GA, Ryan DH. Update on obesity pharmacotherapy. Ann. NY Acad. Sci. 1311, 1–13 (2014).
    • 6 Manning S, Pucci A, Finer N. Pharmacotherapy for obesity: novel agents and paradigms. Ther. Adv. Chronic Dis. 5(3), 135–148 (2014).
    • 7 Li MF, Cheung BM. Rise and fall of anti-obesity drugs. World J. Diabetes 2(2), 19–23 (2011).
    • 8 Wu X, Baig A, Kasymjanova G et al. Pattern of local recurrence and distant metastasis in breast cancer by molecular subtype. Cureus 8(12), e924 (2016).
    • 9 Cheung BMY, Cheung TT, Samaranayake NR. Safety of antiobesity drugs. Ther. Adv. Drug Saf. 4(4), 171–181 (2013).
    • 10 Ng M, Fleming T, Robinson M et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9945), 766–781 (2014).
    • 11 Zheng H, Tumin D, Qian Z. Obesity and mortality risk: new findings from body mass index trajectories. Am. J. Epidemiol. 178(11), 1591–1599 (2013).
    • 12 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J. Clin. 61(2), 69–90 (2011).
    • 13 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J. Clin. 63(1), 11–30 (2013).
    • 14 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 65(2), 87–108 (2015).
    • 15 Baetke SC, Lammers T, Kiessling F. Applications of nanoparticles for diagnosis and therapy of cancer. Br. J. Radiol. 88(1054), 20150207 (2015).
    • 16 Chen WH, Chen JX, Cheng H et al. A new anti-cancer strategy of damaging mitochondria by pro-apoptotic peptide functionalized gold nanoparticles. Chem. Commun. 49, 6403 (2013).
    • 17 Dreaden EC, Austin LA, Mackey MA, El-Sayed MA. Size matters: gold nanoparticles in targeted cancer drug delivery. Ther. Deliv. 3(4), 457–478 (2012).
    • 18 Theek B, Rizzo LY, Ehling J, Kiessling F, Lammers T. The theranostic path to personalized nanomedicine. Clin. Transl. Imaging 2(1), 66–76 (2014).
    • 19 Zhang X. Gold nanoparticles: recent advances in the biomedical applications. Cell Biochem. Biophys. 72, 771–775 (2015).
    • 20 Zdrojewicz Z, Waracki M, Bugaj B, Pypno D, Cabała K. Medical applications of nanotechnology. Postepy Hig. Med. Dosw. 69, 1196–1204 (2015).
    • 21 Dreaden EC, El-Sayed MA. Detecting and destroying cancer cells in more than one way with noble metals and different confinement properties on the nanoscale. Acc. Chem. Res. 45(11), 1854–1865 (2012).
    • 22 Pramanik AK, Siddikuzzaman, Palanimuthu D, Somasundaram K, Samuelson AG. Biotin decorated gold nanoparticles for targeted delivery of a smart-linked anticancer active copper complex: in vitro and in vivo studies. Bioconjug. Chem. 27(12), 2874–2885 (2016).
    • 23 Mieszawska AJ, Mulder WJ, Fayad ZA, Cormode DP. Multifunctional gold nanoparticles for diagnosis and therapy of disease. Mol. Pharm. 10(3), 831–847 (2013).
    • 24 Daraee H, Eatemadi A, Abbasi E, Fekri AS, Kouhi M, Akbarzadeh A. Application of gold nanoparticles in biomedical and drug delivery. Artif. Cells Nanomed. Biotechnol. 44(1), 410–422 (2016).
    • 25 Karmani L, Bouchat V, Bouzin C et al. (89)Zr-labeled anti-endoglin antibody-targeted gold nanoparticles for imaging cancer: implications for future cancer therapy. Nanomedicine 9(13), 1923–1937 (2014).
    • 26 Xiao Z, Levy-Nissenbaum E, Alexis F et al. Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection. ACS Nano 6(1), 696–704 (2012).
    • 27 Chen WH, Luo GF, Xu XD et al. Cancer-targeted functional gold nanoparticles for apoptosis induction and real-time imaging based on FRET. Nanoscale 6(16), 9531–9535 (2014).
    • 28 Meyers JD, Cheng Y, Broome AM et al. Peptide-targeted gold nanoparticles for photodynamic therapy of brain cancer. Part. Part. Syst. Charact. 32(4), 448–457 (2015).
    • 29 Cocco E, Deng Y, Shapiro EM et al. Dual-targeting nanoparticles for in vivo delivery of suicide genes to chemotherapy-resistant ovarian cancer cells. Mol. Cancer Ther. 16(2), 323–333 (2017).
    • 30 Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A. Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers. Drug Des. Dev. Ther. 11, 771–782 (2017).
    • 31 Badr G, Al-Sadoon MK, Raba DM. Therapeutic efficacy and molecular mechanisms of snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles in the treatment of breast cancer- and prostate cancer-bearing experimental mouse models. Free Radic. Biol. Med. 65, 175–89 (2013).
    • 32 Hossen MN, Kajimoto K, Akita H, Hyodo M, Ishitsuka T, Harashima H. Ligand-based targeted delivery of a peptide modified nanocarrier to endothelial cells in adipose tissue. J. Control. Release 147(2), 261–268 (2010). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 33 Thovhogi N, Sibuyi N, Martin O, Meyer M, Madiehe A. Targeted delivery of peptide-functionalized gold nanoparticles to white adipose tissues of obese rats. J. Nanopart. Res. 17, 112 (2015). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 34 Wang F, Wang YC, Dou S et al. Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano 5(5), 3679–3692 (2011).
    • 35 Libutti SK, Paciotti GF, Byrnes AA et al. Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin. Cancer Res. 16(24), 6139–6149 (2010).
    • 36 Clinical Trials database: NCT00356980. https://clinicaltrials.gov/ct2/show/NCT00356980.
    • 37 Clinical Trials database: NCT00436410. https://clinicaltrials.gov/ct2/show/NCT00436410.
    • 38 Clinical Trials database: NCT00848042. https://clinicaltrials.gov/ct2/show/NCT00848042.
    • 39 Kumar A, Ma H, Zhang X et al. Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. Biomaterials 33(4), 1180–1189 (2012). • Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 40 Libutti SK, Paciotti GF, Myer L et al. Results of a completed Phase I clinical trial of CYT-6091: a pegylated colloidal gold-TNF. Nanomedicine 27, 3586 (2009).
    • 41 Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat. Med. 10, 625–632 (2004). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 42 O'Dwyer D, Ralton LD, O'Shea A, Murray GI. The proteomics of colorectal cancer: identification of a protein signature associated with prognosis. PLoS ONE 6(11), e27718 (2011).
    • 43 Zhong N, Cui Y, Zhou X, Li T, Han J. Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS. Tumour Biol. 36(2), 1221–1231 (2015).
    • 44 Gamble SC, Odontiadis M, Waxman J et al. Androgens target prohibitin to regulate proliferation of prostate cancer cells. Oncogene 23, 2996–3004 (2004).
    • 45 Mishra S, Murphy LC, Nyomba BL, Murphy GLJ. Prohibitin: a potential target for new therapeutics. Trends Mol. Med. 11(4), 192–197 (2005).
    • 46 Nijtmans LGJ, de Jong L, Sanz MA et al. Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins. EMBO J. 19(11), 2444–2451 (2000).
    • 47 Artal-Sanz M, Tavernarakis N. Prohibitin and mitochondrial biology. Trends Endocrinol. Metab. 8, 394–401 (2009).
    • 48 Merkwirth C, Langer T. Prohibitin function within mitochondria: essential roles for cell proliferation and cristae morphogenesis. Biochim. Biophys. Acta 1793(1), 27–32 (2009).
    • 49 Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H. Vascular-targeted nanotherapy for obesity: unexpected passive targeting mechanism to obese fat for the enhancement of active drug delivery. J. Control. Release 163, 101–110 (2012). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 50 Kwon MK, Nam JO, Park RW et al. Antitumor effect of a transducible fusogenic peptide releasing multiple proapoptotic peptides by caspase-3. Mol. Cancer Ther. 7(6), 1514–1522 (2008). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 51 Ellerby HM, Arap W, Ellerby LM et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat. Med. 5(9), 1032–1038 (1999). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 52 Javadpour MM, Juban MM, Lo WJ et al. De novo antimicrobial peptides with low mammalian cell toxicity. J. Med. Chem. 39, 3107–3113 (1996). • Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 53 Barnhart KF, Christianson DR, Hanley PW et al. A Peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci. Transl. Med. 3, 108–112 (2011). •• Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.
    • 54 Sosibo NM, Keter FK, Skepu A, Tshikhudo RT. Facile attachment of tat peptide on gold monolayer protected clusters: synthesis and characterization. Nanomaterials 5(3), 1211–1222 (2015).
    • 55 Meyer M, Essack M, Kanyanda S, Rees J. A low-cost flow cytometric assay for the detection and quantification of apoptosis using an anionic halogenated fluorescein dye. Biotechniques 45(3), 317–320 (2008).
    • 56 Clogston JD, Patri AK. Zeta potential measurement. Methods Mol. Biol. 697, 63–70 (2011).
    • 57 Sharma A, Qadri A. Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses. Proc. Natl Acad. Sci. USA 101(50), 17492–17497 (2004).
    • 58 Rastogi S, Joshi B, Dasgupta P, Morris M, Wright K, Chellappan S. Prohibitin facilitates cellular senescence by recruiting specific corepressors to inhibit E2F target genes. Mol. Cell. Biol. 26(11), 4161–4171 (2006).
    • 59 Rastogi S, Joshi B, Fusaro G, Chellappan S. Camptothecin induces nuclear export of prohibitin preferentially in transformed cells through a CRM-1-dependent mechanism. J. Biol. Chem. 281(5), 2951–2959 (2006).
    • 60 Shao X, Schnau P, Qian W, Wang X. Quantitatively understanding cellular uptake of gold nanoparticles via radioactivity analysis. J. Nanosci. Nanotechnol. 15(5), 3834–3838 (2015).
    • 61 Zarska M, Novotny F, Havel F et al. Two-step mechanism of cellular uptake of cationic gold nanoparticles modified by (16 mercaptohexadecyl)trimethylammonium bromide. Bioconjug. Chem. 27(10), 2558–2574 (2016).
    • 62 Perreault A, Richter S, Bergman C, Wuest M, Wuest F. Targeting phosphatidylserine with a 64cu-labeled peptide for molecular imaging of apoptosis. Mol. Pharm. 13(10), 3564–3577 (2016).
    • 63 Loreto C, La Rocca G, Anzalone R et al. The role of intrinsic pathway in apoptosis activation and progression in Peyronie's disease. Biomed. Res. Int. 2014, 616149 (2014).
    • 64 Chen F, Lu X, Yang X et al. Identification of prohibitin as a potential biomarker for colorectal carcinoma based on proteomics technology. Int. J. Oncol. 37(2), 355–365 (2010).
    • 65 Kimura Y, Matsumoto H, Oosawa M et al. Relationship between visceral fat and development of colorectal neoplasms using computed tomographic colonography and adipocytokine levels. Nihon Shokakibyo Gakkai Zasshi 111(11), 2121–2130 (2014).
    • 66 Cao Y. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Chem. Immunol. Allergy 99, 170–179 (2014).
    • 67 Daquinag AC, Zhang Y, Kolonin MG. Vascular targeting of adipose tissue as an anti-obesity approach. Trends Pharmacol. Sci. 32(5), 300–307 (2011). • Proof that vascular-targeted nanotherapies could be a feasible approach for the treatment of chronic diseases.