Skip to main content

Advertisement

SpringerLink
Log in

Synthetic Receptor-Based Targeting Strategies to Improve Tumor Drug Delivery

  • Review Article
  • Theme: NIPTE Research and Perspective: Advances in Nanotechnology-Based Drug Delivery
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Heterogeneity in tumor expression as well as expression in normal tissues of various targets limit the usefulness of current ligand-based active targeting approaches. Incorporation of synthetic receptors, which can be recognized by delivery systems engineered to present specific functional groups on the surface, is a novel approach to improve tumor targeting. Alternatively, introduction of synthetic functionalities on cellular carriers can also enhance tumor targeting. We review various strategies that have been utilized for the introduction of synthetic targets in tumor tissues. The introduction of synthetic functional groups in the tumor through improved strategies is anticipated to result in improved target specificity and reduced heterogeneity in target expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kutova OM, Guryev EL, Sokolova EA, Alzeibak R, Balalaeva IV. Targeted delivery to tumors: multidirectional strategies to improve treatment efficiency. Cancers (Basel). 2019;11(1). https://doi.org/10.3390/cancers11010068.

  2. Zamora AE, Crawford JC, Thomas PG. Hitting the target: how T cells detect and eliminate tumors. J Immunol. 2018;200(2):392–9. https://doi.org/10.4049/jimmunol.1701413.

    Article  CAS  PubMed  Google Scholar 

  3. Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9(1):1410. https://doi.org/10.1038/s41467-018-03705-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Shen J, Hu Y, Putt KS, Singhal S, Han H, Visscher DW, et al. Assessment of folate receptor alpha and beta expression in selection of lung and pancreatic cancer patients for receptor targeted therapies. Oncotarget. 2018;9(4):4485–95. https://doi.org/10.18632/oncotarget.23321.

    Article  PubMed  Google Scholar 

  5. Jabir NR, Tabrez S, Ashraf GM, Shakil S, Damanhouri GA, Kamal MA. Nanotechnology-based approaches in anticancer research. Int J Nanomedicine. 2012;7:4391–408. https://doi.org/10.2147/IJN.S33838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Singh R, Lillard JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86(3):215–23. https://doi.org/10.1016/j.yexmp.2008.12.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Prabhakar U, Maeda H, Jain RK, Sevick-Muraca EM, Zamboni W, Farokhzad OC, et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 2013;73(8):2412–7. https://doi.org/10.1158/0008-5472.Can-12-4561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bisht S, Maitra A. Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009;1(4):415–25. https://doi.org/10.1002/wnan.43.

    Article  CAS  PubMed  Google Scholar 

  9. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007;2(12):751–60.

    Article  CAS  Google Scholar 

  10. Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem. 2016;27(10):2225–38. https://doi.org/10.1021/acs.bioconjchem.6b00437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maeda H. Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88(3):53–71. https://doi.org/10.2183/pjab.88.53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang B, Hu Y, Pang Z. Modulating the tumor microenvironment to enhance tumor nanomedicine delivery. Front Pharmacol. 2017;8:952. https://doi.org/10.3389/fphar.2017.00952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zuo H. iRGD: a promising peptide for cancer imaging and a potential therapeutic agent for various cancers. J Oncol. 2019;2019:9367845–15. https://doi.org/10.1155/2019/9367845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yu W, Liu R, Zhou Y, Gao H. Size-tunable strategies for a tumor targeted drug delivery system. ACS Cent Sci. 2020;6(2):100–16. https://doi.org/10.1021/acscentsci.9b01139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kirtane AR, Sadhukha T, Kim H, Khanna V, Koniar B, Panyam J. Fibrinolytic enzyme cotherapy improves tumor perfusion and therapeutic efficacy of anticancer nanomedicine. Cancer Res. 2017;77(6):1465–75. https://doi.org/10.1158/0008-5472.CAN-16-1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang YR, Lin R, Li HJ, He WL, Du JZ, Wang J. Strategies to improve tumor penetration of nanomedicines through nanoparticle design. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019;11(1):e1519. https://doi.org/10.1002/wnan.1519.

    Article  CAS  PubMed  Google Scholar 

  17. Wong C, Stylianopoulos T, Cui J, Martin J, Chauhan VP, Jiang W, et al. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad Sci U S A. 2011;108(6):2426–31. https://doi.org/10.1073/pnas.1018382108.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kirtane AR, Kalscheuer SM, Panyam J. Exploiting nanotechnology to overcome tumor drug resistance: challenges and opportunities. Adv Drug Deliv Rev. 2013;65(13-14):1731–47. https://doi.org/10.1016/j.addr.2013.09.001.

    Article  CAS  PubMed  Google Scholar 

  19. Song X, Ren Y, Zhang J, Wang G, Han X, Zheng W, et al. Targeted delivery of doxorubicin to breast cancer cells by aptamer functionalized DOTAP/DOPE liposomes. Oncol Rep. 2015;34(4):1953–60. https://doi.org/10.3892/or.2015.4136.

    Article  CAS  PubMed  Google Scholar 

  20. Valetti S, Maione F, Mura S, Stella B, Desmaële D, Noiray M, et al. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor. J Control Release. 2014;192:29–39.

    Article  CAS  Google Scholar 

  21. Lim ZF, Ma PC. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019;12(1):134. https://doi.org/10.1186/s13045-019-0818-2.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature. 2013;501(7467):328–37. https://doi.org/10.1038/nature12624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105–17. https://doi.org/10.1016/j.bbcan.2009.11.002.

    Article  CAS  PubMed  Google Scholar 

  24. Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019;16(6):372–85. https://doi.org/10.1038/s41571-019-0184-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hsiao SC, Shum BJ, Onoe H, Douglas ES, Gartner ZJ, Mathies RA, et al. Direct cell surface modification with DNA for the capture of primary cells and the investigation of myotube formation on defined patterns. Langmuir. 2009;25(12):6985–91. https://doi.org/10.1021/la900150n.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee DY, Park SJ, Nam JH, Byun Y. A new strategy toward improving immunoprotection in cell therapy for diabetes mellitus: long-functioning PEGylated islets in vivo. Tissue Eng. 2006;12(3):615–23. https://doi.org/10.1089/ten.2006.12.615.

    Article  CAS  PubMed  Google Scholar 

  27. Holden CA, Yuan Q, Yeudall WA, Lebman DA, Yang H. Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery. Int J Nanomedicine. 2010;5:25–36.

    Article  CAS  Google Scholar 

  28. Krishnamachari Y, Pearce ME, Salem AK. Self-assembly of cell–microparticle hybrids. Adv Mate. 2008;20(5):989–93. https://doi.org/10.1002/adma.200701689.

    Article  CAS  Google Scholar 

  29. Murciano JC, Medinilla S, Eslin D, Atochina E, Cines DB, Muzykantov VR. Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nat Biotechnol. 2003;21(8):891–6. https://doi.org/10.1038/nbt846.

    Article  CAS  PubMed  Google Scholar 

  30. Sarkar D, Vemula PK, Teo GS, Spelke D, Karnik R, Wee Le Y, et al. Chemical engineering of mesenchymal stem cells to induce a cell rolling response. Bioconjug Chem. 2008;19(11):2105–9. https://doi.org/10.1021/bc800345q.

    Article  CAS  PubMed  Google Scholar 

  31. Boonyarattanakalin S, Athavankar S, Sun Q, Peterson BR. Synthesis of an artificial cell surface receptor that enables oligohistidine affinity tags to function as metal-dependent cell-penetrating peptides. J Am Chem Soc. 2006;128(2):386–7. https://doi.org/10.1021/ja056126j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen A, Zheng G, Tykocinski ML. Hierarchical costimulator thresholds for distinct immune responses: application of a novel two-step Fc fusion protein transfer method. J Immunol. 2000;164(2):705–11. https://doi.org/10.4049/jimmunol.164.2.705.

    Article  CAS  PubMed  Google Scholar 

  33. Chen X, Tam UC, Czlapinski JL, Lee GS, Rabuka D, Zettl A, et al. Interfacing carbon nanotubes with living cells. J Am Chem Soc. 2006;128(19):6292–3. https://doi.org/10.1021/ja060276s.

    Article  CAS  PubMed  Google Scholar 

  34. Chen X, Wu P, Rousseas M, Okawa D, Gartner Z, Zettl A, et al. Boron nitride nanotubes are noncytotoxic and can be functionalized for interaction with proteins and cells. J Am Chem Soc. 2009;131(3):890–1. https://doi.org/10.1021/ja807334b.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Swiston AJ, Cheng C, Um SH, Irvine DJ, Cohen RE, Rubner MF. Surface functionalization of living cells with multilayer patches. Nano Lett. 2008;8(12):4446–53. https://doi.org/10.1021/nl802404h.

    Article  CAS  PubMed  Google Scholar 

  36. Layek B, Sadhukha T, Prabha S. Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors. Biomaterials. 2016;88:97–109. https://doi.org/10.1016/j.biomaterials.2016.02.024.

    Article  CAS  PubMed  Google Scholar 

  37. Layek B, Shetty M, Nethi SK, Sehgal D, Starr TK, Prabha S. Mesenchymal stem cells as guideposts for nanoparticle-mediated targeted drug delivery in ovarian cancer. Cancers. 2020;12(4):965.

    Article  CAS  Google Scholar 

  38. Sampathkumar SG, Li AV, Jones MB, Sun Z, Yarema KJ. Metabolic installation of thiols into sialic acid modulates adhesion and stem cell biology. Nat Chem Biol. 2006;2(3):149–52. https://doi.org/10.1038/nchembio770.

    Article  CAS  PubMed  Google Scholar 

  39. Chen I, Howarth M, Lin W, Ting AY. Site-specific labeling of cell surface proteins with biophysical probes using biotin ligase. Nat Methods. 2005;2(2):99–104. https://doi.org/10.1038/nmeth735.

    Article  CAS  PubMed  Google Scholar 

  40. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73. https://doi.org/10.1126/scitranslmed.3002842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–33. https://doi.org/10.1056/NEJMoa1103849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chambers E, Mitragotri S. Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J Control Release. 2004;100(1):111–9. https://doi.org/10.1016/j.jconrel.2004.08.005.

    Article  CAS  PubMed  Google Scholar 

  43. Thierry B, Winnik FM, Merhi Y, Tabrizian M. Nanocoatings onto arteries via layer-by-layer deposition: toward the in vivo repair of damaged blood vessels. J Am Chem Soc. 2003;125(25):7494–5. https://doi.org/10.1021/ja034321x.

    Article  CAS  PubMed  Google Scholar 

  44. Ukidve A, Zhao Z, Fehnel A, Krishnan V, Pan DC, Gao Y, et al. Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function. Proc Natl Acad Sci U S A. 2020;117(30):17727–36. https://doi.org/10.1073/pnas.2002880117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wilson JT, Krishnamurthy VR, Cui W, Qu Z, Chaikof EL. Noncovalent cell surface engineering with cationic graft copolymers. J Am Chem Soc. 2009;131(51):18228–9. https://doi.org/10.1021/ja908887v.

    Article  CAS  PubMed  Google Scholar 

  46. Chuah MK, Collen D, VandenDriessche T. Biosafety of adenoviral vectors. Curr Gene Ther. 2003;3(6):527–43. https://doi.org/10.2174/1566523034578140.

    Article  CAS  PubMed  Google Scholar 

  47. Halim L, Maher J. CAR T-cell immunotherapy of B-cell malignancy: the story so far. Ther Adv Vaccines Immunother. 2020;8:2515135520927164. https://doi.org/10.1177/2515135520927164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yip A, Webster RM. The market for chimeric antigen receptor T cell therapies. Nat. Rev. Drug Discov. 2018;17(3):161–2. https://doi.org/10.1038/nrd.2017.266.

    Article  CAS  PubMed  Google Scholar 

  49. Choe JH, Williams JZ, Lim WA. Engineering T cells to treat cancer: the convergence of immuno-oncology and synthetic biology. Annu Rev Cancer Biol. 2020;4(1):121–39. https://doi.org/10.1146/annurev-cancerbio-030419-033657.

    Article  Google Scholar 

  50. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–50. https://doi.org/10.1038/s41591-018-0014-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cerwenka A, Lanier LL. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 2016;16(2):112–23.

    Article  CAS  Google Scholar 

  52. Jiang H, Zhang W, Shang P, Zhang H, Fu W, Ye F, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8(2):297–310. https://doi.org/10.1016/j.molonc.2013.12.001.

    Article  CAS  PubMed  Google Scholar 

  53. Chu J, Deng Y, Benson DM, He S, Hughes T, Zhang J, et al. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia. 2014;28(4):917–27. https://doi.org/10.1038/leu.2013.279.

    Article  CAS  PubMed  Google Scholar 

  54. Zhang X, Wang J, Chen Z, Hu Q, Wang C, Yan J, et al. Engineering PD-1-presenting platelets for cancer immunotherapy. Nano Lett. 2018;18(9):5716–25. https://doi.org/10.1021/acs.nanolett.8b02321.

    Article  CAS  PubMed  Google Scholar 

  55. Wang C, Sun W, Ye Y, Hu Q, Bomba HN, Gu Z. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat Biomed Eng. 2017;1(2):0011. https://doi.org/10.1038/s41551-016-0011.

    Article  CAS  Google Scholar 

  56. Zhang X, Yao S, Liu C, Jiang Y. Tumor tropic delivery of doxorubicin-polymer conjugates using mesenchymal stem cells for glioma therapy. Biomaterials. 2015;39:269–81. https://doi.org/10.1016/j.biomaterials.2014.11.003.

    Article  CAS  PubMed  Google Scholar 

  57. Wang X, Gao J, Ouyang X, Wang J, Sun X, Lv Y. Mesenchymal stem cells loaded with paclitaxel-poly(lactic-co-glycolic acid) nanoparticles for glioma-targeting therapy. Int J Nanomedicine. 2018;13:5231–48. https://doi.org/10.2147/IJN.S167142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sadhukha T, O'Brien TD, Prabha S. Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release. 2014;196:243–51.

    Article  CAS  Google Scholar 

  59. Li L, Guan Y, Liu H, Hao N, Liu T, Meng X, et al. Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS Nano. 2011;5(9):7462–70. https://doi.org/10.1021/nn202399w.

    Article  CAS  PubMed  Google Scholar 

  60. Hadrys A, Sochanik A, McFadden G, Jazowiecka-Rakus J. Mesenchymal stem cells as carriers for systemic delivery of oncolytic viruses. Eur J Pharmacol. 2020;874:172991. https://doi.org/10.1016/j.ejphar.2020.172991.

    Article  CAS  PubMed  Google Scholar 

  61. Komarova S, Roth J, Alvarez R, Curiel DT, Pereboeva L. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. J Ovarian Res. 2010;3:12. https://doi.org/10.1186/1757-2215-3-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Stephan MT, Irvine DJ. Enhancing Cell therapies from the Outside In: Cell Surface Engineering Using Synthetic Nanomaterials. Nano Today. 2011;6(3):309–25. https://doi.org/10.1016/j.nantod.2011.04.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Stephan MT, Moon JJ, Um SH, Bershteyn A, Irvine DJ. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med. 2010;16(9):1035–41. https://doi.org/10.1038/nm.2198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Smith WJ, Tran H, Griffin JI, Jones J, Vu VP, Nilewski L, et al. Lipophilic indocarbocyanine conjugates for efficient incorporation of enzymes, antibodies and small molecules into biological membranes. Biomaterials. 2018;161:57–68. https://doi.org/10.1016/j.biomaterials.2018.01.029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kavanaugh JS, Flack CE, Lister J, Ricker EB, Ibberson CB, Jenul C, et al. Identification of extracellular DNA-binding proteins in the biofilm matrix. mBio. 2019;10(3). https://doi.org/10.1128/mBio.01137-19.

  66. Matsusaki M, Akashi M. Cell surface engineering using a layer-by-layer nanofilm for biomedical applications. Cell surface engineering: fabrication of functional nanoshells: Royal Society of Chemistry; 2014. p. 216-239.

  67. Boonyarattanakalin S, Martin SE, Sun Q, Peterson BR. A synthetic mimic of human Fc receptors: defined chemical modification of cell surfaces enables efficient endocytic uptake of human immunoglobulin-G. J Am Chem Soc. 2006;128(35):11463–70. https://doi.org/10.1021/ja062377w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Niu J, Lunn DJ, Pusuluri A, Yoo JI, O'Malley MA, Mitragotri S, et al. Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization. Nat Chem. 2017;9(6):537–45. https://doi.org/10.1038/nchem.2713.

    Article  CAS  PubMed  Google Scholar 

  69. Paderi J, Prestwich GD, Panitch A, Boone T, Stuart K. Glycan therapeutics: resurrecting an almost Pharma-Forgotten Drug Class. Adv Ther-Germany. 2018;1(8):2. https://doi.org/10.1002/adtp.201800082.

    Article  Google Scholar 

  70. Moh ESX, Sayyadi N, Packer NH. Chemoenzymatic glycan labelling as a platform for site-specific IgM-antibody drug conjugates. Anal Biochem. 2019;584:113385. https://doi.org/10.1016/j.ab.2019.113385.

    Article  CAS  PubMed  Google Scholar 

  71. Kayser H, Zeitler R, Kannicht C, Grunow D, Nuck R, Reutter W. Biosynthesis of a nonphysiological sialic acid in different rat organs, using N-propanoyl-D-hexosamines as precursors. J Biol Chem. 1992;267(24):16934–8.

    Article  CAS  Google Scholar 

  72. Agatemor C, Buettner MJ, Ariss R, Muthiah K, Saeui CT, Yarema KJ. Exploiting metabolic glycoengineering to advance healthcare. Nat Rev Chem. 2019;3(10):605–20. https://doi.org/10.1038/s41570-019-0126-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem. 1991;266(8):4706–12.

    Article  CAS  Google Scholar 

  74. Keppler OT, Stehling P, Herrmann M, Kayser H, Grunow D, Reutter W, et al. Biosynthetic modulation of sialic acid-dependent virus-receptor interactions of two primate polyoma viruses. J Biol Chem. 1995;270(3):1308–14. https://doi.org/10.1074/jbc.270.3.1308.

    Article  CAS  PubMed  Google Scholar 

  75. Sletten EM, Bertozzi CR. Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed Engl. 2009;48(38):6974–98. https://doi.org/10.1002/anie.200900942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kang SW, Lee S, Na JH, Yoon HI, Lee DE, Koo H, et al. Cell labeling and tracking method without distorted signals by phagocytosis of macrophages. Theranostics. 2014;4(4):420–31. https://doi.org/10.7150/thno.7265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Koo H, Lee S, Na JH, Kim SH, Hahn SK, Choi K, et al. Bioorthogonal copper-free click chemistry in vivo for tumor-targeted delivery of nanoparticles. Angew Chem Int Ed Engl. 2012;51(47):11836–40. https://doi.org/10.1002/anie.201206703.

    Article  CAS  PubMed  Google Scholar 

  78. Best MD. Click chemistry and bioorthogonal reactions: unprecedented selectivity in the labeling of biological molecules. Biochemistry. 2009;48(28):6571–84. https://doi.org/10.1021/bi9007726.

    Article  CAS  PubMed  Google Scholar 

  79. Lee S, Koo H, Na JH, Han SJ, Min HS, Lee SJ, et al. Chemical tumor-targeting of nanoparticles based on metabolic glycoengineering and click chemistry. ACS Nano. 2014;8(3):2048–63. https://doi.org/10.1021/nn406584y.

    Article  CAS  PubMed  Google Scholar 

  80. Cheng S, Nethi SK, Rathi S, Layek B, Prabha S. Engineered mesenchymal stem cells for targeting solid tumors: therapeutic potential beyond regenerative therapy. J Pharmacol Exp Ther. 2019;370(2):231–41. https://doi.org/10.1124/jpet.119.259796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Heidari R, Gholamian Dehkordi N, Mohseni R, Safaei M. Engineering mesenchymal stem cells: a novel therapeutic approach in breast cancer. J Drug Target. 2020;28(7-8):732–41. https://doi.org/10.1080/1061186X.2020.1775842.

    Article  CAS  PubMed  Google Scholar 

  82. Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984;44(2):753–60.

    CAS  PubMed  Google Scholar 

  83. Gan HK, Kaye AH, Luwor RB. The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci. 2009;16(6):748–54. https://doi.org/10.1016/j.jocn.2008.12.005.

    Article  CAS  PubMed  Google Scholar 

  84. Balyasnikova IV, Ferguson SD, Sengupta S, Han Y, Lesniak MS. Mesenchymal stem cells modified with a single-chain antibody against EGFRvIII successfully inhibit the growth of human xenograft malignant glioma. PLoS One. 2010;5(3):e9750. https://doi.org/10.1371/journal.pone.0009750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kalimuthu S, Oh JM, Gangadaran P, Zhu L, Lee HW, Rajendran RL, et al. In vivo tracking of chemokine receptor CXCR4-engineered mesenchymal stem cell migration by optical molecular imaging. Stem Cells Int. 2017;2017:8085637–10. https://doi.org/10.1155/2017/8085637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Marquez-Curtis LA, Gul-Uludag H, Xu P, Chen J, Janowska-Wieczorek A. CXCR4 transfection of cord blood mesenchymal stromal cells with the use of cationic liposome enhances their migration toward stromal cell-derived factor-1. Cytotherapy. 2013;15(7):840–9. https://doi.org/10.1016/j.jcyt.2013.02.009.

    Article  CAS  PubMed  Google Scholar 

  87. Heidari P, Kunawudhi A, Martinez-Quintanilla J, Szretter A, Shah K, Mahmood U. Somatostatin receptor type 2 as a radiotheranostic PET reporter gene for oncologic interventions. Theranostics. 2018;8(12):3380–91. https://doi.org/10.7150/thno.24017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nelson CA, Azure MT, Adams CT, Zinn KR. The somatostatin analog 188Re-P2045 inhibits the growth of AR42J pancreatic tumor xenografts. J Nucl Med. 2014;55(12):2020–5. https://doi.org/10.2967/jnumed.114.140780.

    Article  CAS  PubMed  Google Scholar 

  89. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl. 2001;40(11):2004–21. https://doi.org/10.1002/1521-3773.

    Article  CAS  PubMed  Google Scholar 

  90. Hsu TL, Hanson SR, Kishikawa K, Wang SK, Sawa M, Wong CH. Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells. Proc Natl Acad Sci U S A. 2007;104(8):2614–9. https://doi.org/10.1073/pnas.0611307104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Debets MF, van Berkel SS, Dommerholt J, Dirks AT, Rutjes FP, van Delft FL. Bioconjugation with strained alkenes and alkynes. Acc Chem Res. 2011;44(9):805–15. https://doi.org/10.1021/ar200059z.

    Article  CAS  PubMed  Google Scholar 

  92. Willems LI, Verdoes M, Florea BI, van der Marel GA, Overkleeft HS. Two-step labeling of endogenous enzymatic activities by Diels-Alder ligation. Chembiochem. 2010;11(12):1769–81. https://doi.org/10.1002/cbic.201000280.

    Article  CAS  PubMed  Google Scholar 

  93. Dommerholt J, Schmidt S, Temming R, Hendriks LJ, Rutjes FP, van Hest JC, et al. Readily accessible bicyclononynes for bioorthogonal labeling and three-dimensional imaging of living cells. Angew Chem Int Ed Engl. 2010;49(49):9422–5. https://doi.org/10.1002/anie.201003761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lang K, Davis L, Wallace S, Mahesh M, Cox DJ, Blackman ML, et al. Genetic Encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions. J Am Chem Soc. 2012;134(25):10317–20. https://doi.org/10.1021/ja302832g.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Natunen S, Lampinen M, Suila H, Ritamo I, Pitkanen V, Nairn AV, et al. Metabolic glycoengineering of mesenchymal stromal cells with N-propanoylmannosamine. Glycobiology. 2013;23(8):1004–12. https://doi.org/10.1093/glycob/cwt039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Layek B, Sadhukha T, Panyam J, Prabha S. Nano-engineered mesenchymal stem cells increase therapeutic efficacy of anticancer drug through true active tumor targeting. Mol Cancer Ther. 2018;17(6):1196–206. https://doi.org/10.1158/1535-7163.MCT-17-0682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hart C, Chase LG, Hajivandi M, Agnew B. Metabolic labeling and click chemistry detection of glycoprotein markers of mesenchymal stem cell differentiation. Methods Mol Biol. 2011;698:459–84. https://doi.org/10.1007/978-1-60761-999-4_33.

    Article  CAS  PubMed  Google Scholar 

  98. Layek B, Sehgal D, Argenta PA, Panyam J, Prabha S. Nanoengineering of mesenchymal stem cells via surface modification for efficient cancer therapy. Adv Ther-Germany. 2019;2(9):1900043. https://doi.org/10.1002/adtp.201900043.

    Article  CAS  Google Scholar 

Download references

Funding

Funding support received from National Institute of Health (EB022558).

Author information

Author notes

    Authors and Affiliations

    1. Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, 19140, USA

      Susheel Kumar Nethi & Swayam Prabha

    2. School of Pharmacy, Temple University, Philadelphia, Pennsylvania, 19140, USA

      Shubhmita Bhatnagar

    3. Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, 19140, USA

      Swayam Prabha

    Authors
    1. Susheel Kumar Nethi
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Shubhmita Bhatnagar
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Swayam Prabha
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Swayam Prabha.

    Ethics declarations

    Disclaimer

    All the authors alone are responsible for the content and writing of this article.

    Conflict of Interest

    The authors declare that they have no conflict of interest.

    Additional information

    Susheel Kumar Nethi and Shubhmita Bhatnagar contributed equally to this work.

    Publisher’s Note

    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Nethi, S.K., Bhatnagar, S. & Prabha, S. Synthetic Receptor-Based Targeting Strategies to Improve Tumor Drug Delivery. AAPS PharmSciTech 22, 93 (2021). https://doi.org/10.1208/s12249-021-01919-w

    Download citation

    • Received:

    • Accepted:

    • Published:

    • DOI: https://doi.org/10.1208/s12249-021-01919-w

    KEY WORDS

    Search

    Navigation