Abstract
A paradigm transition in cancer treatment gradually moved from "one drug-one target" toward "multi-target selective drugs design", because different drugs simultaneously inhibit tumor progression differently. The underlying mechanism has encountered significant challenges, such as encapsulating chemotherapies into a nanosized particulate system, adverse side effects, and managing multidrug-resistant. To address these issues, herein we engineered the gold nanoparticles’ surfaces with cross-linked polyethylene glycol that have well-controlled morphology and further encapsulated with commonly known chemo-drugs paclitaxel and bleomycin for nanovectorization of therapeutics to the intended site and there act through the concurrent action of dual targeting mechanisms without creating undesired side effects. The structures of the nanovectorization particulate system were confirmed by various spectroscopic techniques. The efficacy of nanovectorization particulate system and non-targeted free drugs was evaluated using the human cervical adenocarcinoma cell model. Our findings indicate that this nanovectorization particulate system had synergic stimuli-responsive characteristics and unrivaled control of efficient transportation of therapeutics agents. This system meets the high demand for multiple targeting delivery and has substantial benefits across multiple fields of nanomedicine, especially in chemotherapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and materials
The data and materials, used in completing this research work, are available from the corresponding author on reasonable request.
References
Aryal S, Grailer JJ, Pilla S, Steeber DA, Gong S (2009) Doxorubicin conjugated gold nanoparticles as water-soluble and pH-responsive anticancer drug nanocarriers. J Mater Chem 19(42):7879. https://doi.org/10.1039/b914071a
Bessar H, Venditti I, Benassi L, Vaschieri C, Azzoni P, Pellacani G, Magnoni C, Botti E, Casagrande V, Federici M, Costanzo A, Fontana L, Testa G, Mostafa FF, Ibrahim SA, Russo MV, Fratoddi I (2016) Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis. Colloids Surf B 141:141–147. https://doi.org/10.1016/j.colsurfb.2016.01.021
Bodelón G, Costas C, Pérez-Juste J, Pastoriza-Santos I, Liz-Marzán LM (2017) Gold nanoparticles for regulation of cell function and behavior. Nano Today 13:40–60. https://doi.org/10.1016/j.nantod.2016.12.014
Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38(6):1759–1782. https://doi.org/10.1039/b806051g
Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsague X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjose S, authors of ICOMCCoHPVI, Related Diseases Vaccine Volume S (2013) Comprehensive control of human papillomavirus infections and related diseases. Vaccine 31(Suppl 7):H1-31. https://doi.org/10.1016/j.vaccine.2013.10.003
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Bukowski K, Kciuk M, Kontek R (2020) Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci. https://doi.org/10.3390/ijms21093233
Cabuzu D, Cirja A, Puiu R, Grumezescu AM (2015) Biomedical applications of gold nanoparticles. Curr Top Med Chem 15(16):1605–1613. https://doi.org/10.2174/1568026615666150414144750
Cheng Y, Doane TL, Chuang CH, Ziady A, Burda C (2014) Near infrared light-triggered drug generation and release from gold nanoparticle carriers for photodynamic therapy. Small 10(9):1799–1804. https://doi.org/10.1002/smll.201303329
Cohen PA, Jhingran A, Oaknin A, Denny L (2019) Cervical cancer. The Lancet 393(10167):169–182. https://doi.org/10.1016/s0140-6736(18)32470-x
Cuong HN, Pansambal S, Ghotekar S, Oza R, Thanh Hai NT, Viet NM, Nguyen VH (2022) New frontiers in the plant extract mediated biosynthesis of copper oxide (CuO) nanoparticles and their potential applications: a review. Environ Res 203:111858. https://doi.org/10.1016/j.envres.2021.111858
Dabhane H, Ghotekar S, Tambade P, Pansambal S, Murthy HCA, Oza R, Medhane V (2021) A review on environmentally benevolent synthesis of CdS nanoparticle and their applications. Environ Chem Ecotox 3:209–219. https://doi.org/10.1016/j.enceco.2021.06.002
Ding Y, Zhou YY, Chen H, Geng DD, Wu DY, Hong J, Shen WB, Hang TJ, Zhang C (2013) The performance of thiol-terminated PEG-paclitaxel-conjugated gold nanoparticles. Biomaterials 34(38):10217–10227. https://doi.org/10.1016/j.biomaterials.2013.09.008
Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA (2012) The golden age: gold nanoparticles for biomedicine. Chem Soc Rev 41(7):2740–2779. https://doi.org/10.1039/c1cs15237h
Duenas-Gonzalez A, Campbell S (2016) Global strategies for the treatment of early-stage and advanced cervical cancer. Curr Opin Obstet Gynecol 28(1):11–17. https://doi.org/10.1097/GCO.0000000000000234
Elahi N, Kamali M, Baghersad MH (2018) Recent biomedical applications of gold nanoparticles: a review. Talanta 184:537–556. https://doi.org/10.1016/j.talanta.2018.02.088
Elit LM, Hirte H (2014) Management of advanced or recurrent cervical cancer: chemotherapy and beyond. Expert Rev Anticancer Ther 14(3):319–332. https://doi.org/10.1586/14737140.2014.866041
England CG, Miller MC, Kuttan A, Trent JO, Frieboes HB (2015) Release kinetics of paclitaxel and cisplatin from two and three layered gold nanoparticles. Eur J Pharm Biopharm 92:120–129. https://doi.org/10.1016/j.ejpb.2015.02.017
Fan C, Wang S, Hong JW, Bazan GC, Plaxco KW, Heeger AJ (2003) Beyond superquenching: hyper-efficient energy transfer from conjugated polymers to gold nanoparticles. Proc Natl Acad Sci USA 100(11):6297–6301. https://doi.org/10.1073/pnas.1132025100
Farooq MU, Naz MY, Hussain MI, Shukrullah S, Makhlouf MM (2021) Smart therapeutic strategy of pH-responsive gold nanoparticles for combating multidrug resistance. Part Part Syst Charact 38(7):2100073. https://doi.org/10.1002/ppsc.202100073
Fede C, Fortunati I, Weber V, Rossetto N, Bertasi F, Petrelli L, Guidolin D, Signorini R, De Caro R, Albertin G, Ferrante C (2015) Evaluation of gold nanoparticles toxicity towards human endothelial cells under static and flow conditions. Microvasc Res 97:147–155. https://doi.org/10.1016/j.mvr.2014.10.010
Fratoddi I, Venditti I, Cametti C, Russo MV (2015) The puzzle of toxicity of gold nanoparticles. The case-study of HeLa cells. Toxicol Res 4(4):796–800. https://doi.org/10.1039/c4tx00168k
Gallud A, Kloditz K, Ytterberg J, Ostberg N, Katayama S, Skoog T, Gogvadze V, Chen YZ, Xue D, Moya S, Ruiz J, Astruc D, Zubarev R, Kere J, Fadeel B (2019) Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study. Sci Rep 9(1):4366. https://doi.org/10.1038/s41598-019-40579-6
Garcia-Gradilla V, Sattayasamitsathit S, Soto F, Kuralay F, Yardimci C, Wiitala D, Galarnyk M, Wang J (2014) Ultrasound-propelled nanoporous gold wire for efficient drug loading and release. Small 10(20):4154–4159. https://doi.org/10.1002/smll.201401013
Gehlen MH (2020) The centenary of the Stern-Volmer equation of fluorescence quenching: from the single line plot to the SV quenching map. J Photochem Photobiol C 42:100338. https://doi.org/10.1016/j.jphotochemrev.2019.100338
Ghotekar S, Pansambal S, Bilal M, Pingale SS, Oza R (2021) Environmentally friendly synthesis of Cr2O3 nanoparticles: characterization, applications and future perspective—a review. CSCEE 3:100089. https://doi.org/10.1016/j.cscee.2021.100089
Goodman CM, McCusker CD, Yilmaz T, Rotello VM (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15(4):897–900. https://doi.org/10.1021/bc049951i
Harush-Frenkel O, Debotton N, Benita S, Altschuler Y (2007) Targeting of nanoparticles to the clathrin-mediated endocytic pathway. Biochem Biophys Res Commun 353(1):26–32. https://doi.org/10.1016/j.bbrc.2006.11.135
Inkpen MS, Liu ZF, Li H, Campos LM, Neaton JB, Venkataraman L (2019) Non-chemisorbed gold-sulfur binding prevails in self-assembled monolayers. Nat Chem 11(4):351–358. https://doi.org/10.1038/s41557-019-0216-y
Kalia R, Chauhan A, Verma R, Sharma M, Batoo KM, Kumar R, Hussain S, Ghotekar S, Ijaz MF (2022) Photocatalytic degradation properties of Li-Cr Ions substituted CoFe2O4 nanoparticles for wastewater treatment application. Physica Status Solidi (a) 219(8):2100539. https://doi.org/10.1002/pssa.202100539
Kashid Y, Ghotekar S, Bilal M, Pansambal S, Oza R, Varma RS, Nguyen V-H, Ananda Murthy HC, Mane D (2022) Bio-inspired sustainable synthesis of silver chloride nanoparticles and their prominent applications. J Indian Chem Soc 99(5):100335. https://doi.org/10.1016/j.jics.2021.100335
Khandelia R, Jaiswal A, Ghosh SS, Chattopadhyay A (2013) Gold nanoparticle-protein agglomerates as versatile nanocarriers for drug delivery. Small 9(20):3494–3505. https://doi.org/10.1002/smll.201203095
Khare S, Williams K, Gokulan K (2014) Nanotechnology. In: Encyclopedia of food microbiology, 2nd edn. Elsevier, Amsterdam, pp 893–900
Koshkaryev A, Piroyan A, Torchilin VP (2013) Bleomycin in octaarginine-modified fusogenic liposomes results in improved tumor growth inhibition. Cancer Lett 334(2):293–301. https://doi.org/10.1016/j.canlet.2012.06.008
Lee JM, Minasian L, Kohn EC (2019) New strategies in ovarian cancer treatment. Cancer 125(Suppl 24):4623–4629. https://doi.org/10.1002/cncr.32544
Lin Y-W, Huang C-C, Chang H-T (2011) Gold nanoparticle probes for the detection of mercury, lead and copper ions. Analyst 136(5):863–871. https://doi.org/10.1039/c0an00652a
Lin C-J, Kuan C-H, Wang L-W, Wu H-C, Chen Y, Chang C-W, Huang R-Y, Wang T-W (2016) Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics. Biomaterials 90:12–26. https://doi.org/10.1016/j.biomaterials.2016.03.005
Liu D, Wang Z, Jiang X (2011) Gold nanoparticles for the colorimetric and fluorescent detection of ions and small organic molecules. Nanoscale 3(4):1421–1433. https://doi.org/10.1039/c0nr00887g
Lurie JM, Weidman A, Huynh S, Delgado D, Easthausen I, Kaur G (2020) Painful gynecologic and obstetric complications of female genital mutilation/cutting: A systematic review and meta-analysis. PLoS Med 17(3):e1003088. https://doi.org/10.1371/journal.pmed.1003088
Manivasagan P, Bharathiraja S, Bui NQ, Lim IG, Oh J (2016) Paclitaxel-loaded chitosan oligosaccharide-stabilized gold nanoparticles as novel agents for drug delivery and photoacoustic imaging of cancer cells. Int J Pharm 511(1):367–379. https://doi.org/10.1016/j.ijpharm.2016.07.025
Markman JL, Rekechenetskiy A, Holler E, Ljubimova JY (2013) Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv Drug Deliv Rev 65(13–14):1866–1879. https://doi.org/10.1016/j.addr.2013.09.019
Maysinger D, Gran ER, Bertorelle F, Fakhouri H, Antoine R, Kaul ES, Samhadaneh DM, Stochaj U (2020) Gold nanoclusters elicit homeostatic perturbations in glioblastoma cells and adaptive changes of lysosomes. Theranostics 10(4):1633–1648. https://doi.org/10.7150/thno.37674
Morth C, Valachis A (2014) Single-agent versus combination chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and performance status 2: a literature-based meta-analysis of randomized studies. Lung Cancer 84(3):209–214. https://doi.org/10.1016/j.lungcan.2014.03.015
Muddineti OS, Ghosh B, Biswas S (2015) Current trends in using polymer coated gold nanoparticles for cancer therapy. Int J Pharm 484(1–2):252–267
Pautier P, Gutierrez-Bonnaire M, Rey A, Sillet-Bach I, Chevreau C, Kerbrat P, Morice P, Duvillard P, Lhomme C (2008) Combination of bleomycin, etoposide, and cisplatin for the treatment of advanced ovarian granulosa cell tumors. Int J Gynecol Cancer 18(3):446–452. https://doi.org/10.1111/j.1525-1438.2007.01049.x
Pawar SK, Vavia P (2015) Efficacy interactions of PEG-DOX-N-acetyl glucosamine prodrug conjugate for anticancer therapy. Eur J Pharm Biopharm 97(Pt B):454–463. https://doi.org/10.1016/j.ejpb.2015.07.019
Pusuluri A, Wu D, Mitragotri S (2019) Immunological consequences of chemotherapy: Single drugs, combination therapies and nanoparticle-based treatments. J Control Release 305:130–154. https://doi.org/10.1016/j.jconrel.2019.04.020
Ren F, Shen J, Shi H, Hornicek FJ, Kan Q, Duan Z (2016) Novel mechanisms and approaches to overcome multidrug resistance in the treatment of ovarian cancer. Biochim Biophys Acta 2:266–275. https://doi.org/10.1016/j.bbcan.2016.10.001
Rignall A (2017) ICHQ1A(R2) stability testing of new drug substance and product and ICHQ1C stability testing of new dosage forms. Wiley, Hoboken. https://doi.org/10.1002/9781118971147.ch1
Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM (2018) Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer 18(7):452–464. https://doi.org/10.1038/s41568-018-0005-8
Sankaranarayanan R, Ferlay J (2006) Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 20(2):207–225. https://doi.org/10.1016/j.bpobgyn.2005.10.007
Wang W, Wang J, Ding Y (2020a) Gold nanoparticle-conjugated nanomedicine: design, construction, and structure-efficacy relationship studies. J Mater Chem B 8(22):4813–4830. https://doi.org/10.1039/c9tb02924a
Wang Z, Dong J, Zhao Q, Ying Y, Zhang L, Zou J, Zhao S, Wang J, Zhao Y, Jiang S (2020b) Gold nanoparticlemediated delivery of paclitaxel and nucleic acids for cancer therapy (Review). Mol Med Rep 22(6):4475–4484. https://doi.org/10.3892/mmr.2020.11580
Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL (2015) Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 136(2):189–197. https://doi.org/10.1016/j.ygyno.2014.11.076
Yang C, Uertz J, Chithrani DB (2016) Colloidal gold-mediated delivery of bleomycin for improved outcome in chemotherapy. Nanomaterials. https://doi.org/10.3390/nano6030048
Yang C, Bromma K, Di Ciano-Oliveira C, Zafarana G, van Prooijen M, Chithrani DB (2018) Gold nanoparticle mediated combined cancer therapy. Cancer Nanotechnol. https://doi.org/10.1186/s12645-018-0039-3
Yang M, Li J, Gu P, Fan X (2021) The application of nanoparticles in cancer immunotherapy: targeting tumor microenvironment. Bioact Mater 6(7):1973–1987. https://doi.org/10.1016/j.bioactmat.2020.12.010
Zhou H, Xu H, Li X, Lv Y, Ma T, Guo S, Huang Z, Wang X, Xu P (2017) Dual targeting hyaluronic acid - RGD mesoporous silica coated gold nanorods for chemo-photothermal cancer therapy. Mater Sci Eng C Mater Biol Appl 81:261–270. https://doi.org/10.1016/j.msec.2017.08.002
Acknowledgements
Taif University Researchers Supporting Project Number (TURSP-2020/165), Taif University, Taif, Saudi Arabia.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
This manuscript is free from any known conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Farooq, M.U., Sahin, Y.M., Naz, M.Y. et al. Surface engineered AuNPs for paclitaxel-loaded bleomycin delivery as a supplementation therapy. Appl Nanosci 12, 3883–3899 (2022). https://doi.org/10.1007/s13204-022-02645-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13204-022-02645-w