Current and Future Aspects of Smart Nanotheranostic Agents in Cancer Therapeutics

  • Qurrat Ul Ain


Despite the wide range of knowledge and information about cancer and advances in its treatment, still it is among the leading cause of mortality. Scientists around the globe are working on developing the new strategies to combat this fatal disease, and fortunately significant advances have already been achieved. In this regard, nanomedicines can play a vital role by improving the bio-distribution and the target site delivery of chemotherapeutics. Along with therapeutic applications, nanomedicine formulations have been used for imaging purposes as well. Nanotheranostics is a relatively new but flourishing field, which combines the diagnosis and therapy for personalized treatment. Combining the nanomaterials of diverse origins, e.g., polymers, liposomes, micelles, and antibodies, scientists have successfully developed the smart nanoparticles for both diagnostics and therapeutics at the same time in vivo. In addition, theranostics can be conjugated with bio-ligands for targeted drug delivery to treat and monitor the treatment response at molecular level. Potential applications of nanotheranostic medicines are assessment of drug biodistribution, site-targeted drug delivery, and visualization of drug release at the delivery site. These applications help to optimize the strategies based on triggered drug release and the prediction of therapeutic responses. In the near future, nanotheranostics are the practical solution for cancer and other lethal diseases to cure or at least treat them in the early stage.

This chapter summarizes the smart nanoparticles, developed for the simultaneous imaging and therapy, approaches for their targeted delivery, current applications and the challenges in their development and future perspectives for cancer therapy.


Cancer Nanotheranostics Chemotherapy Nanoparticles 


  1. Baksh K, Weber J. Immune checkpoint protein inhibition for cancer: preclinical justification for CTLA-4 and PD-1 blockade and new combinations. Semin Oncol. 2015;42(3):363–77.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Bardhan R, Lal S, Joshi A, Halas NJ. Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc Chem Res. 2011;44(10):936–46.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bertoli G, Cava C, Castiglioni I. MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 2015;5(10):1122.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bhakta-Guha D, Saeed M, Greten H, Efferth T. Dis-organizing centrosomal clusters: specific cancer therapy for a generic spread? Curr Med Chem. 2015;22(6):685–94.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Brydøy M, Fosså SD, Dahl O, Bjøro T. Gonadal dysfunction and fertility problems in cancer survivors. Acta Oncol. 2007;46(4):480–9.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Bucci MK, Bevan A, Roach M. Advances in radiation therapy: conventional to 3D, to IMRT, to 4D, and beyond. CA Cancer J Clin. 2005;55(2):117–34.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Cao Y, Xu L, Kuang Y, Xiong D, Pei R. Gadolinium-based nanoscale MRI contrast agents for tumor imaging. J Mater Chem B. 2017;5(19):3431–61.CrossRefGoogle Scholar
  8. Carretero C, Munoz-Navas M, Betes M, Angos R, Subtil JC, Fernandez-Urien I, De la Riva S, Sola J, Bilbao JI, De Luis E. Gastroduodenal injury after radioembolization of hepatic tumors. Am J Gastroenterol. 2007;102(6):1216.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Chen N-T, Cheng S-H, Souris JS, Chen C-T, Mou C-Y, Lo L-W. Theranostic applications of mesoporous silica nanoparticles and their organic/inorganic hybrids. J Mater Chem B. 2013;1(25):3128–35.CrossRefGoogle Scholar
  10. Cheng S-H, Lee C-H, Chen M-C, Souris JS, Tseng F-G, Yang C-S, Mou C-Y, Chen C-T, Lo L-W. Tri-functionalization of mesoporous silica nanoparticles for comprehensive cancer theranostics—the trio of imaging, targeting and therapy. J Mater Chem. 2010;20(29):6149–57.CrossRefGoogle Scholar
  11. Choi KY, Liu G, Lee S, Chen X. Theranostic nanoplatforms for simultaneous cancer imaging and therapy: current approaches and future perspectives. Nanoscale. 2012;4(2):330–42.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Conde J, Edelman ER, Artzi N. Target-responsive DNA/RNA nanomaterials for microRNA sensing and inhibition: The jack-of-all-trades in cancer nanotheranostics? Adv Drug Deliv Rev. 2015;81:169–83.PubMedCrossRefPubMedCentralGoogle Scholar
  13. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.CrossRefPubMedGoogle Scholar
  14. Draz MS, Fang BA, Zhang P, Hu Z, Gu S, Weng KC, Gray JW, Chen FF. Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics. 2014;4(9):872.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Elad S, Zadik Y, Hewson I, Hovan A, Correa MEP, Logan R, Elting LS, Spijkervet FK, Brennan MT. A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea. Support Care Cancer. 2010;18(8):993–1006.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Esteva A, Kuprel B, Novoa RA, Ko J, Swetter SM, Blau HM, Thrun S. Dermatologist-level classification of skin cancer with deep neural networks. Nature. 2017;542(7639):115.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Fernandez-Fernandez A, Manchanda R, McGoron AJ. Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Appl Biochem Biotechnol. 2011;165(7–8):1628–51.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Funkhouser J. Reinventing pharma: the theranostic revolution. Curr Drug Discov. 2002;2:17–9.Google Scholar
  19. Gibson RJ, Keefe DM. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer. 2006;14(9):890.PubMedCrossRefPubMedCentralGoogle Scholar
  20. He Q, Ma M, Wei C, Shi J. Mesoporous carbon@ silicon-silica nanotheranostics for synchronous delivery of insoluble drugs and luminescence imaging. Biomaterials. 2012;33(17):4392–402.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Howell M, Valle JW. The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol. 2015;29(2):333–43.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng G-S. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21(3):389–401.e381.CrossRefGoogle Scholar
  23. Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010;62(11):1052–63.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Kateb B, Chiu K, Black KL, Yamamoto V, Khalsa B, Ljubimova JY, Ding H, Patil R, Portilla-Arias JA, Modo M. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? NeuroImage. 2011;54:S106–24.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Keidan RD, Fanning J, Gatenby RA, Weese JL. Recurrent typhlitis. Dis Colon Rectum. 1989;32(3):206–9.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Kirschbaum SE, Baeumner AJ. A review of electrochemiluminescence (ECL) in and for microfluidic analytical devices. Anal Bioanal Chem. 2015;407(14):3911–26.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Koo Y-EL, Reddy GR, Bhojani M, Schneider R, Philbert MA, Rehemtulla A, Ross BD, Kopelman R. Brain cancer diagnosis and therapy with nanoplatforms. Adv Drug Deliv Rev. 2006;58(14):1556–77.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Kulke MH, Siu LL, Tepper JE, Fisher G, Jaffe D, Haller DG, Ellis LM, Benedetti JK, Bergsland EK, Hobday TJ. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting. J Clin Oncol. 2011;29(7):934.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Kumar R, Kulkarni A, Nagesha DK, Sridhar S. In vitro evaluation of theranostic polymeric micelles for imaging and drug delivery in cancer. Theranostics. 2012;2(7):714.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Landry B, Valencia-Serna J, Gul-Uludag H, Jiang X, Janowska-Wieczorek A, Brandwein J, Uludag H. Progress in RNAi-mediated molecular therapy of acute and chronic myeloid leukemia. Mol Ther Nucleic Acids. 2015;4:e240.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Lee HS, Park JY, Shin SH, Kim SB, Lee JS, Lee A, Ye BJ, Kim YS. Herpesviridae viral infections after chemotherapy without antiviral prophylaxis in patients with malignant lymphoma: incidence and risk factors. Am J Clin Oncol. 2012a;35(2):146–50.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Lee VH, Ng SC, Leung T, Au GK, Kwong DL. Dosimetric predictors of radiation-induced acute nausea and vomiting in IMRT for nasopharyngeal cancer. Int J Radiat Oncol Biol Phys. 2012b;84(1):176–82.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Lee J-H, Chae J-W, Kim JK, Kim HJ, Chung JY, Kim Y-H. Inhibition of cisplatin-resistance by RNA interference targeting metallothionein using reducible oligo-peptoplex. J Control Release. 2015;215:82–90.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Li S, Goins B, Zhang L, Bao A. Novel multifunctional theranostic liposome drug delivery system: construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging. Bioconjug Chem. 2012;23(6):1322–32.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33(6):654.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Ma X, Tao H, Yang K, Feng L, Cheng L, Shi X, Li Y, Guo L, Liu Z. A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Res. 2012;5(3):199–212.CrossRefGoogle Scholar
  38. Malvezzi M, Carioli G, Bertuccio P, Negri E, La Vecchia C. Relation between mortality trends of cardiovascular diseases and selected cancers in the European Union, in 1970–2017. Focus on cohort and period effects. Eur J Cancer. 2018;103:341–55.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Miao W, Shim G, Kim G, Lee S, Lee H-J, Kim YB, Byun Y, Oh Y-K. Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets. J Control Release. 2015;211:28–36.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Mitra RN, Doshi M, Zhang X, Tyus JC, Bengtsson N, Fletcher S, Page BD, Turkson J, Gesquiere AJ, Gunning PT. An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery. Biomaterials. 2012;33(5):1500–8.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Moon H, Yoon C, Lee TW, Ha K-S, Chang JH, Song T-K, Kim K, Kim H. Therapeutic ultrasound contrast agents for the enhancement of tumor diagnosis and tumor therapy. J Biomed Nanotechnol. 2015;11(7):1183–92.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Moreno BH, Parisi G, Robert L, Ribas A. Anti-PD-1 therapy in melanoma. Semin Oncol. 2015;42(3):466–73.CrossRefGoogle Scholar
  43. Mukherjee S, Chowdhury D, Kotcherlakota R, Patra S. Potential theranostics application of bio-synthesized silver nanoparticles (4-in-1 system). Theranostics. 2014;4(3):316.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Muthu MS, Kulkarni SA, Raju A, Feng S-S. Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dots. Biomaterials. 2012;33(12):3494–501.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Novoselov K, Jiang D, Schedin F, Booth T, Khotkevich V, Morozov S, Geim A. Two-dimensional atomic crystals. Proc Natl Acad Sci. 2005;102(30):10451–3.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Ramage JK, Donaghy A, Farrant JM, Iorns R, Williams R. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology. 1995;108(3):865–9.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Rastogi R, Gulati N, Kotnala RK, Sharma U, Jayasundar R, Koul V. Evaluation of folate conjugated pegylated thermosensitive magnetic nanocomposites for tumor imaging and therapy. Colloids Surf B Biointerfaces. 2011;82(1):160–7.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro RJ, Mosquera J-M, Montgomery B, Taplin M-E, Pritchard CC, Attard G. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215–28.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Sailor MJ, Park JH. Hybrid nanoparticles for detection and treatment of cancer. Adv Mater. 2012;24(28):3779–802.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Santra S, Kaittanis C, Grimm J, Perez JM. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small. 2009;5(16):1862–8.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Sen K, Mandal M. Second generation liposomal cancer therapeutics: transition from laboratory to clinic. Int J Pharm. 2013;448(1):28–43.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Shi X, Gong H, Li Y, Wang C, Cheng L, Liu Z. Graphene-based magnetic plasmonic nanocomposite for dual bioimaging and photothermal therapy. Biomaterials. 2013;34(20):4786–93.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Taratula O, Patel M, Schumann C, Naleway MA, Pang AJ, He H, Taratula O. Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy. Int J Nanomed. 2015;10:2347.CrossRefGoogle Scholar
  56. Vivero-Escoto JL, Huang Y-T. Inorganic-organic hybrid nanomaterials for therapeutic and diagnostic imaging applications. Int J Mol Sci. 2011;12(6):3888–927.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Wang L-S, Chuang M-C, Ho J-aA. Nanotheranostics—a review of recent publications. Int J Nanomed. 2012;7:4679.Google Scholar
  58. Wang L, Xing H, Zhang S, Ren Q, Pan L, Zhang K, Bu W, Zheng X, Zhou L, Peng W. A Gd-doped Mg-Al-LDH/Au nanocomposite for CT/MR bimodal imagings and simultaneous drug delivery. Biomaterials. 2013;34(13):3390–401.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Weigelt B, Peterse JL, Van’t Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5(8):591.CrossRefPubMedGoogle Scholar
  60. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the US Preventive Services Task Force. Ann Intern Med. 2008;149(9):638–58.PubMedCrossRefPubMedCentralGoogle Scholar
  61. WHO. Cancer fact sheet N 297. 2015.Google Scholar
  62. Wolinsky JB, Grinstaff MW. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Deliv Rev. 2008;60(9):1037–55.PubMedCrossRefPubMedCentralGoogle Scholar
  63. World Health Organization. Cancer fact sheet. Updated Feb 2017.Google Scholar
  64. Xie J, Lee S, Chen X. Nanoparticle-based theranostic agents. Adv Drug Deliv Rev. 2010;62(11):1064–79.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Xie J, Liu G, Eden HS, Ai H, Chen X. Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. Acc Chem Res. 2011;44(10):883–92.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Yallapu MM, Othman SF, Curtis ET, Gupta BK, Jaggi M, Chauhan SC. Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials. 2011;32(7):1890–905.PubMedCrossRefPubMedCentralGoogle Scholar
  67. Yang K, Hu L, Ma X, Ye S, Cheng L, Shi X, Li C, Li Y, Liu Z. Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles. Adv Mater. 2012;24(14):1868–72.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Yuan J, Zhang H, Kaur H, Oupicky D, Peng F. Synthesis and characterization of theranostic poly (HPMA)-c (RGDyK)-DOTA-64Cu copolymer targeting tumor angiogenesis: tumor localization visualized by positron emission tomography. Mol Imaging. 2013;12(3):203–12.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Zedan AF, Moussa S, Terner J, Atkinson G, El-Shall MS. Ultrasmall gold nanoparticles anchored to graphene and enhanced photothermal effects by laser irradiation of gold nanostructures in graphene oxide solutions. ACS Nano. 2012;7(1):627–36.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Zhang L, Gu F, Chan J, Wang A, Langer R, Farokhzad O. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761–9.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Zhang MH, Man HT, Zhao XD, Dong N, Ma SL. Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials. Biomed Rep. 2014;2(1):41–52.PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Qurrat Ul Ain
    • 1
  1. 1.Department of Molecular MedicineNational University of Medical SciencesRawalpindiPakistan

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