Pattern recognition receptors on innate immune cells play an important role in guiding how cells interact with the rest of the organism and in determining the direction of the downstream immune response. Recent advances have elucidated the structure and function of these receptors, providing new opportunities for developing targeted drugs and vaccines to treat infections, cancers, and neurological disorders. C-type lectin receptors, Toll-like receptors, and folate receptors have attracted interest for their ability to endocytose their ligands or initiate signaling pathways that influence the immune response. Several novel technologies are being developed to engage these receptors, including recombinant antibodies, adoptive immunotherapy, and chemically modified antigens and drug delivery vehicles. These active targeting technologies will help address current challenges facing drug and vaccine delivery and lead to new tools to treat human diseases.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Adiseshaiah PP, Hall JB, McNeil SE. 1.  2010. Nanomaterial standards for efficacy and toxicity assessment. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2:99–112 [Google Scholar]
  2. van Vliet SJ, García-Vallejo JJ, van Kooyk Y. 2.  2008. Dendritic cells and C-type lectin receptors: coupling innate to adaptive immune responses. Immunol. Cell Biol. 86:580–87 [Google Scholar]
  3. Zamze S, Martinez-Pomares L, Jones H, Taylor PR, Stillion RJ. 3.  et al. 2002. Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the macrophage mannose receptor. J. Biol. Chem. 277:41613–23 [Google Scholar]
  4. Fiani ML, Beitz J, Turvy D, Blum JS, Stahl PD. 4.  1998. Regulation of mannose receptor synthesis and turnover in mouse J774 macrophages. J. Leukoc. Biol. 64:85–91 [Google Scholar]
  5. de Veerdonk FL, Marijnissen RJ, Kullberg BJ, Koenen HJ, Cheng SC. 5.  van et al. 2009. The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe 5:329–40 [Google Scholar]
  6. Lee SJ, Evers S, Roeder D, Parlow AF, Risteli J. 6.  et al. 2002. Mannose receptor–mediated regulation of serum glycoprotein homeostasis. Science 295:1898–901 [Google Scholar]
  7. Gadjeva M, Takahashi K, Thiel S. 7.  2004. Mannan-binding lectin—a soluble pattern recognition molecule. Mol. Immunol. 41:113–21 [Google Scholar]
  8. Ma YG, Cho MY, Zhao M, Park JW, Matsushita M. 8.  et al. 2004. Human mannose-binding lectin and l-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement. J. Biol. Chem. 279:25307–12 [Google Scholar]
  9. Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J. 9.  et al. 2008. Mannose-binding lectin (MBL)-associated serine protease (MASP) 1 contributes to activation of the lectin complement pathway. J. Immunol. 180:6132–38 [Google Scholar]
  10. Tacken PJ, de Vries IJ, Torensma R, Figdor CG. 10.  2007. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat. Rev. Immunol. 7:790–802 [Google Scholar]
  11. Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL. 11.  et al. 2000. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II–positive lysosomal compartments. J. Cell Biol. 151:673–84 [Google Scholar]
  12. Kato M, McDonald KJ, Khan S, Ross IL, Vuckovic S. 12.  et al. 2006. Expression of human DEC-205 (CD205) multilectin receptor on leukocytes. Int. Immunol. 18:857–69 [Google Scholar]
  13. Gliddon DR, Hope JC, Brooke GP, Howard CJ. 13.  2004. DEC-205 expression on migrating dendritic cells in afferent lymph. Immunology 111:262–72 [Google Scholar]
  14. Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G. 14.  et al. 2010. Targeting of DEC-205 on human dendritic cells results in efficient MHC class II–restricted antigen presentation. Blood 116:2277–85 [Google Scholar]
  15. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. 15.  2002. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196:1627–38 [Google Scholar]
  16. Geijtenbeek TB, van Vliet SJ, Engering A, 't Hart BA, van Kooyk Y. 16.  2004. Self- and nonself-recognition by C-type lectins on dendritic cells. Annu. Rev. Immunol. 22:33–54 [Google Scholar]
  17. Tabarani G, Reina JJ, Ebel C, Vives C, Lortat-Jacob H. 17.  et al. 2006. Mannose hyperbranched dendritic polymers interact with clustered organization of DC-SIGN and inhibit gp120 binding. FEBS Lett. 580:2402–8 [Google Scholar]
  18. Feinberg H, Guo Y, Mitchell DA, Drickamer K, Weis WI. 18.  2005. Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR. J. Biol. Chem. 280:1327–35 [Google Scholar]
  19. Azad AK, Torrelles JB, Schlesinger LS. 19.  2008. Mutation in the DC-SIGN cytoplasmic triacidic cluster motif markedly attenuates receptor activity for phagocytosis and endocytosis of mannose-containing ligands by human myeloid cells. J. Leukoc. Biol. 84:1594–603 [Google Scholar]
  20. Reid DM, Montoya M, Taylor PR, Borrow P, Gordon S. 20.  et al. 2004. Expression of the β-glucan receptor, dectin-1, on murine leukocytes in situ correlates with its function in pathogen recognition and reveals potential roles in leukocyte interactions. J. Leukoc. Biol. 76:86–94 [Google Scholar]
  21. Herre J, Marshall AS, Caron E, Edwards AD, Williams DL. 21.  et al. 2004. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 104:4038–45 [Google Scholar]
  22. Gringhuis SI, Wevers BA, Kaptein TM, van Capel TM, Theelen B. 22.  et al. 2011. Selective C-Rel activation via Malt1 controls anti-fungal TH-17 immunity by dectin-1 and dectin-2. PLOS Pathog. 7:e1001259 [Google Scholar]
  23. O'Neill LA, Golenbock D, Bowie AG. 23.  2013. The history of Toll-like receptors—redefining innate immunity. Nat. Rev. Immunol. 13:453–60 [Google Scholar]
  24. Baumann CL, Aspalter IM, Sharif O, Pichlmair A, Blüml S. 24.  et al. 2010. CD14 is a coreceptor of Toll-like receptors 7 and 9. J. Exp. Med. 207:2689–701 [Google Scholar]
  25. Bernasconi NL, Onai N, Lanzavecchia A. 25.  2003. A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood 101:4500–4 [Google Scholar]
  26. Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY. 26.  2004. TLR2 is expressed on activated T cells as a costimulatory receptor. PNAS 101:3029–34 [Google Scholar]
  27. Núñez MR, Wong J, Westoll JF, Brooks HJ, O'Neill LA. 27.  et al. 2007. A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins. PLOS ONE 2:e788 [Google Scholar]
  28. Lebeis SL, Bommarius B, Parkos CA, Sherman MA, Kalman D. 28.  2007. TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium. J. Immunol. 179:566–77 [Google Scholar]
  29. Higgins SC, Jarnicki AG, Lavelle EC, Mills KH. 29.  2006. TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J. Immunol. 177:7980–89 [Google Scholar]
  30. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP. 30.  et al. 2000. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 1:398–401 [Google Scholar]
  31. Alderson MR, McGowan P, Baldridge JR, Probst P. 31.  2006. TLR4 agonists as immunomodulatory agents. J. Endotoxin Res. 12:313–19 [Google Scholar]
  32. Ohashi K, Burkart V, Flohe S, Kolb H. 32.  2000. Cutting edge: Heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor 4 complex. J. Immunol. 164:558–61 [Google Scholar]
  33. Farhat K, Riekenberg S, Heine H, Debarry J, Lang R. 33.  et al. 2008. Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. J. Leukoc. Biol. 83:692–701 [Google Scholar]
  34. Yoon SI, Kurnasov O, Natarajan V, Hong M, Gudkov AV. 34.  et al. 2012. Structural basis of TLR5–flagellin recognition and signaling. Science 335:859–64 [Google Scholar]
  35. Van Maele L, Carnoy C, Cayet D, Songhet P, Dumoutier L. 35.  et al. 2010. TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3negCD127+ immune cells in spleen and mucosa. J. Immunol. 185:1177–85 [Google Scholar]
  36. Stahl-Hennig C, Eisenblätter M, Jasny E, Rzehak T, Tenner-Racz K. 36.  et al. 2009. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLOS Pathog. 5:e1000373 [Google Scholar]
  37. Liu L, Botos I, Wang Y, Leonard JN, Shiloach J. 37.  et al. 2008. Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320:379–81 [Google Scholar]
  38. Jelinek I, Leonard JN, Price GE, Brown KN, Meyer-Manlapat A. 38.  et al. 2011. TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J. Immunol. 186:2422–29 [Google Scholar]
  39. Chen K, Xiang Y, Yao X, Liu Y, Gong W. 39.  et al. 2011. The active contribution of Toll-like receptors to allergic airway inflammation. Int. Immunopharmacol. 11:1391–98 [Google Scholar]
  40. Iwasaki A, Medzhitov R. 40.  2015. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16:343–53 [Google Scholar]
  41. Re F, Strominger JL. 41.  2004. IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J. Immunol. 173:7548–55 [Google Scholar]
  42. Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC. 42.  et al. 2005. Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J. Immunol. 174:1259–68 [Google Scholar]
  43. Simchoni N, Cunningham-Rundles C. 43.  2015. TLR7- and TLR9-responsive human B cells share phenotypic and genetic characteristics. J. Immunol. 194:3035–44 [Google Scholar]
  44. Franchi L, Warner N, Viani K, Nuñez G. 44.  2009. Function of Nod-like receptors in microbial recognition and host defense. Immunol. Rev. 227:106–28 [Google Scholar]
  45. van Stijn CM, Meyer S, van den Broek M, Bruijns SC, van Kooyk Y. 45.  et al. 2010. Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN. Mol. Immunol. 47:1544–52 [Google Scholar]
  46. Varghese B, Vlashi E, Xia W, Ayala Lopez W, Paulos CM. 46.  et al. 2014. Folate receptor-β in activated macrophages: ligand binding and receptor recycling kinetics. Mol. Pharm. 11:3609–16 [Google Scholar]
  47. Sabharanjak S, Mayor S. 47.  2004. Folate receptor endocytosis and trafficking. Adv. Drug Deliv. Rev. 56:1099–109 [Google Scholar]
  48. Gonen N, Assaraf YG. 48.  2012. Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist. Updates 15:183–210 [Google Scholar]
  49. Hilgenbrink AR, Low PS. 49.  2005. Folate receptor–mediated drug targeting: from therapeutics to diagnostics. J. Pharm. Sci. 94:2135–46 [Google Scholar]
  50. Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID. 50.  2008. The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol. Pharmacol. 74:854–62 [Google Scholar]
  51. Wang Y, Zhao R, Goldman ID. 51.  2004. Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier. Clin. Cancer Res. 10:6256–64 [Google Scholar]
  52. Assaraf YG, Leamon CP, Reddy JA. 52.  2014. The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resist. Updates 17:89–95 [Google Scholar]
  53. Wen Y, Graybill WS, Previs RA, Hu W, Ivan C. 53.  et al. 2014. Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer. Clin. Cancer Res. 15:448–59 [Google Scholar]
  54. Shen J, Hilgenbrink AR, Xia W, Feng Y, Dimitrov DS. 54.  et al. 2014. Folate receptor-β constitutes a marker for human proinflammatory monocytes. J. Leukoc. Biol. 96:563–70 [Google Scholar]
  55. Lu J, Pang Y, Xie F, Guo H, Li Y. 55.  et al. 2011. Synthesis and in vitro/in vivo evaluation of 99mTc-labeled folate conjugates for folate receptor imaging. Nucl. Med. Biol. 38:557–65 [Google Scholar]
  56. Muller C, Schibli R. 56.  2011. Folic acid conjugates for nuclear imaging of folate receptor–positive cancer. J. Nucl. Med. 52:1–4 [Google Scholar]
  57. Lu Y, Stinnette TW, Westrick E, Klein PJ, Gehrke MA. 57.  et al. 2011. Treatment of experimental adjuvant arthritis with a novel folate receptor–targeted folic acid–aminopterin conjugate. Arthritis Res. Ther. 13:R56 [Google Scholar]
  58. Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS. 58.  et al. 2013. Structural basis for molecular recognition of folic acid by folate receptors. Nature 500:486–89 [Google Scholar]
  59. Wibowo AS, Singh M, Reeder KM, Carter JJ, Kovach AR. 59.  et al. 2013. Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. PNAS 110:15180–88 [Google Scholar]
  60. van der Meel R, Vehmeijer LJ, Kok RJ, Storm G, van Gaal EV. 60.  2013. Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status. Adv. Drug Deliv. Rev. 65:1284–98 [Google Scholar]
  61. Hesse C, Ginter W, Förg T, Mayer CT, Baru AM. 61.  et al. 2013. In vivo targeting of human DC-SIGN drastically enhances CD8+ T-cell-mediated protective immunity. Eur. J. Immunol. 43:2543–53 [Google Scholar]
  62. Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I. 62.  et al. 2011. Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. PNAS 108:2384–89 [Google Scholar]
  63. Cheong C, Choi JH, Vitale L, He LZ, Trumpfheller C. 63.  et al. 2010. Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116:3828–38 [Google Scholar]
  64. Hogarth PM, Pietersz GA. 64.  2012. Fc receptor–targeted therapies for the treatment of inflammation, cancer and beyond. Nat. Rev. Drug Discov. 11:311–31 [Google Scholar]
  65. Hong Y, Peng Y, Xiao H, Mi M, Munn D, He Y. 65.  2012. Immunoglobulin Fc fragment tagging allows strong activation of endogenous CD4 T cells to reshape the tumor milieu and enhance the antitumor effect of lentivector immunization. J. Immunol. 188:4819–27 [Google Scholar]
  66. Rawool DB, Bitsaktsis C, Li Y, Gosselin DR, Lin Y. 66.  et al. 2008. Utilization of Fc receptors as a mucosal vaccine strategy against an intracellular bacterium, Francisella tularensis. J. Immunol. 180:5548–57 [Google Scholar]
  67. Ejaz A, Ammann CG, Werner R, Huber G, Oberhauser V. 67.  et al. 2012. Targeting viral antigens to CD11c on dendritic cells induces retrovirus-specific T cell responses. PLOS ONE 7:e45102 [Google Scholar]
  68. Castro FV, Tutt AL, White AL, Teeling JL, James S. 68.  et al. 2008. CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses. Eur. J. Immunol. 38:2263–73 [Google Scholar]
  69. Daniels TR, Delgado T, Helguera G, Penichet ML. 69.  2006. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clin. Immunol. 121:159–76 [Google Scholar]
  70. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M. 70.  et al. 2006. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16 [Google Scholar]
  71. Lin J, Spidel JL, Maddage CJ, Rybinski KA, Kennedy RP. 71.  et al. 2013. The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity. Cancer Biol. Ther. 14:1032–38 [Google Scholar]
  72. Carter PJ, Senter PD. 72.  2008. Antibody–drug conjugates for cancer therapy. Cancer J. 14:154–69 [Google Scholar]
  73. Carter PJ.73.  2006. Potent antibody therapeutics by design. Nat. Rev. Immunol. 6:343–57 [Google Scholar]
  74. Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC. 74.  2005. Monoclonal antibody successes in the clinic. Nat. Biotechnol. 23:1073–78 [Google Scholar]
  75. Palmer DH, Midgley RS, Mirza N, Torr EE, Ahmed F. 75.  et al. 2009. A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology 49:124–32 [Google Scholar]
  76. Raïch-Regué D, Naranjo-Gómez M, Grau-López L, Ramo C, Pujol-Borrell R. 76.  et al. 2012. Differential effects of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. Vaccine 30:378–87 [Google Scholar]
  77. Fučíková J, Rožková D, Ulčová H, Budinský V, Sochorová K. 77.  et al. 2011. Poly I:C–activated dendritic cells that were generated in CellGro for use in cancer immunotherapy trials. J. Transl. Med. 9:223 [Google Scholar]
  78. Thomas-Kaskel AK, Zeiser R, Jochim R, Robbel C, Schultze-Seemann W. 78.  et al. 2006. Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival. Int. J. Cancer 119:2428–34 [Google Scholar]
  79. Restifo NP, Dudley ME, Rosenberg SA. 79.  2012. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat. Rev. Immunol. 12:269–81 [Google Scholar]
  80. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS. 80.  et al. 2011. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 17:4550–57 [Google Scholar]
  81. Kondo H, Hazama S, Kawaoka T, Yoshino S, Yoshida S. 81.  et al. 2008. Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. Anticancer Res. 28:379–87 [Google Scholar]
  82. Adams EW, Ratner DM, Seeberger PH, Hacohen N. 82.  2008. Carbohydrate-mediated targeting of antigen to dendritic cells leads to enhanced presentation of antigen to T cells. ChemBioChem 9:294–303 [Google Scholar]
  83. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S. 83.  et al. 2004. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199:815–24 [Google Scholar]
  84. Carrillo-Conde B, Song EH, Chavez-Santoscoy A, Phanse Y, Ramer-Tait AE. 84.  et al. 2011. Mannose-functionalized “pathogen-like” polyanhydride nanoparticles target C-type lectin receptors on dendritic cells. Mol. Pharm. 8:1877–86 [Google Scholar]
  85. Singh SK, Stephani J, Schaefer M, Kalay H, García-Vallejo JJ. 85.  et al. 2009. Targeting glycan modified OVA to murine DC-SIGN transgenic dendritic cells enhances MHC class I and II presentation. Mol. Immunol. 47:164–74 [Google Scholar]
  86. Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, van Kooyk Y. 86.  2011. Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int. J. Cancer 128:1371–83 [Google Scholar]
  87. Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C. 87.  et al. 2009. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat. Biotechnol. 27:925–32 [Google Scholar]
  88. Higgins SC, Mills KH. 88.  2010. TLR, NLR agonists, and other immune modulators as infectious disease vaccine adjuvants. Curr. Infect. Dis. Rep. 12:4–12 [Google Scholar]
  89. Kufer TA, Sansonetti PJ. 89.  2007. Sensing of bacteria: NOD a lonely job. Curr. Opin. Microbiol. 10:62–69 [Google Scholar]
  90. Vecchi S, Bufali S, Uno T, Wu T, Arcidiacono L. 90.  et al. 2014. Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model. Eur. J. Pharm. Biopharm. 87:310–17 [Google Scholar]
  91. Ambrosio AJ, Suzin D, Palmer EL, Penson RT. 91.  2014. Vintafolide (EC145) for the treatment of folate-receptor-α-positive platinum-resistant ovarian cancer. Expert Rev. Clin. Pharmacol. 7:443–50 [Google Scholar]
  92. Jia F, Liu X, Li L, Mallapragada S, Narasimhan B, Wang Q. 92.  2013. Multifunctional nanoparticles for targeted delivery of immune activating and cancer therapeutic agents. J. Control. Release 172:1020–34 [Google Scholar]
  93. Phanse Y, Carrillo-Conde BR, Ramer-Tait AE, Roychoudhury R, Pohl NL. 93.  et al. 2013. Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells. Acta Biomater. 9:8902–9 [Google Scholar]
  94. Chavez-Santoscoy AV, Roychoudhury R, Pohl NL, Wannemuehler MJ, Narasimhan B, Ramer-Tait AE. 94.  2012. Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using “pathogen-like” amphiphilic polyanhydride nanoparticles. Biomaterials 33:4762–72 [Google Scholar]
  95. Goodman JT, Vela Ramirez JE, Boggiatto PM, Roychoudhury R, Pohl NL. 95.  et al. 2014. Nanoparticle chemistry and functionalization differentially regulates dendritic cell–nanoparticle interactions and triggers dendritic cell maturation. Part. Part. Syst. Charact. 31:11 [Google Scholar]
  96. Vela-Ramirez JE, Goodman JT, Boggiatto PM, Roychoudhury R, Pohl NL. 96.  et al. 2014. Safety and biocompatibility of carbohydrate-functionalized polyanhydride nanoparticles. AAPS J. 17:256–67 [Google Scholar]
  97. Tamayo I, Irache JM, Mansilla C, Ochoa-Repáraz J, Lasarte JJ, Gamazo C. 97.  2010. Poly(anhydride) nanoparticles act as active Th1 adjuvants through Toll-like receptor exploitation. Clin. Vaccine Immunol. 17:1356–62 [Google Scholar]
  98. Raghuwanshi D, Mishra V, Das D, Kaur K, Suresh MR. 98.  2012. Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein. Mol. Pharm. 9:946–56 [Google Scholar]
  99. Demento SL, Bonafe N, Cui W, Kaech SM, Caplan MJ. 99.  et al. 2010. TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis. J. Immunol. 185:2989–97 [Google Scholar]
  100. Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A. 100.  2005. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J. Exp. Med. 202:1715–24 [Google Scholar]
  101. Fahmy TM, Samstein RM, Harness CC, Saltzman MW. 101.  2005. Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting. Biomaterials 26:5727–36 [Google Scholar]
  102. de Titta A, Ballester M, Julier Z, Nembrini C, Jeanbart L. 102.  et al. 2013. Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose. PNAS 110:19902–7 [Google Scholar]
  103. Pavot V, Rochereau N, Primard C, Genin C, Perouzel E. 103.  et al. 2013. Encapsulation of Nod1 and Nod2 receptor ligands into poly(lactic acid) nanoparticles potentiates their immune properties. J. Control. Release 167:60–67 [Google Scholar]
  104. Jena PK, Singh S, Prajapati B, Nareshkumar G, Mehta T, Seshadri S. 104.  2014. Impact of targeted specific antibiotic delivery for gut microbiota modulation on high-fructose-fed rats. Appl. Biochem. Biotechnol. 172:3810–26 [Google Scholar]
  105. Xiong MH, Li YJ, Bao Y, Yang XZ, Hu B, Wang J. 105.  2012. Bacteria-responsive multifunctional nanogel for targeted antibiotic delivery. Adv. Mater. 24:6175–80 [Google Scholar]
  106. Zhang L, Pornpattananangku D, Hu CM, Huang CM. 106.  2010. Development of nanoparticles for antimicrobial drug delivery. Curr. Med. Chem. 17:585–94 [Google Scholar]
  107. Toti US, Guru BR, Hali M, McPharlin CM, Wykes SM. 107.  et al. 2011. Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles. Biomaterials 32:6606–13 [Google Scholar]
  108. Montes-Worboys A, Brown S, Regev D, Bellew BF, Mohammed KA. 108.  et al. 2010. Targeted delivery of amikacin into granuloma. Am. J. Respir. Crit. Care Med. 182:1546–53 [Google Scholar]
  109. Skountzou I, del Pilar Martin, Wang B, Ye L, Koutsonanos D. 109.  et al. 2010. Salmonella flagellins are potent adjuvants for intranasally administered whole inactivated influenza vaccine. Vaccine 28:4103–12 [Google Scholar]
  110. Turley CB, Rupp RE, Johnson C, Taylor DN, Wolfson J. 110.  et al. 2011. Safety and immunogenicity of a recombinant M2e–flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine 29:5145–52 [Google Scholar]
  111. Treanor JJ, Taylor DN, Tussey L, Hay C, Nolan C. 111.  et al. 2010. Safety and immunogenicity of a recombinant hemagglutinin influenza–flagellin fusion vaccine (VAX125) in healthy young adults. Vaccine 28:8268–74 [Google Scholar]
  112. Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ. 112.  et al. 2010. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLOS ONE 5:e13677 [Google Scholar]
  113. Ichinohe T, Watanabe I, Ito S, Fujii H, Moriyama M. 113.  et al. 2005. Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection. J. Virol. 79:2910–19 [Google Scholar]
  114. Urban P, Valle-Delgado JJ, Mauro N, Marques J, Manfredi A. 114.  et al. 2014. Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium. J. Control. Release 177:84–95 [Google Scholar]
  115. Movellan J, Urban P, Moles E, de la Fuente JM, Sierra T. 115.  et al. 2014. Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs. Biomaterials 35:7940–50 [Google Scholar]
  116. Marques J, Moles E, Urban P, Prohens R, Busquets MA. 116.  et al. 2014. Application of heparin as a dual agent with antimalarial and liposome targeting activities toward Plasmodium-infected red blood cells. Nanomedicine 10:1719–28 [Google Scholar]
  117. Rosenholm J, Sahlgren C, Lindén M. 117.  2010. Cancer-cell targeting and cell-specific delivery by mesoporous silica nanoparticles. J. Mater. Chem. 20:2707–13 [Google Scholar]
  118. Brannon-Peppas L, Blanchette JO. 118.  2004. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev. 56:1649–59 [Google Scholar]
  119. Danhier F, Feron O, Préat V. 119.  2010. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J. Control. Release 148:135–46 [Google Scholar]
  120. Chan JM, Rhee JW, Drum CL, Bronson RT, Golomb G. 120.  et al. 2011. In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid-polymeric nanoparticles. PNAS 108:19347–52 [Google Scholar]
  121. Bhojani MS, Van Dort M, Rehemtulla A, Ross BD. 121.  2010. Targeted imaging and therapy of brain cancer using theranostic nanoparticles. Mol. Pharm. 7:1921–29 [Google Scholar]
  122. Guo XX, He W, Zhang XJ, Hu XM. 122.  2013. Cytotoxicity of cationic liposomes coated by N-trimethyl chitosan and their in vivo tumor angiogenesis targeting containing doxorubicin. J. Appl. Polym. Sci. 128:21–27 [Google Scholar]
  123. Brigger I, Dubernet C, Couvreur P. 123.  2002. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev. 54:631–51 [Google Scholar]
  124. Na JH, Koo H, Lee S, Min KH, Park K. 124.  et al. 2011. Real-time and non-invasive optical imaging of tumor-targeting glycol chitosan nanoparticles in various tumor models. Biomaterials 32:5252–61 [Google Scholar]
  125. Gao J, Chen K, Xie R, Xie J, Lee S. 125.  et al. 2010. Ultrasmall near-infrared non-cadmium quantum dots for in vivo tumor imaging. Small 6:256–61 [Google Scholar]
  126. Wang F, Zhang D, Zhang Q, Chen Y, Zheng D. 126.  et al. 2011. Synergistic effect of folate-mediated targeting and verapamil-mediated P-gp inhibition with paclitaxel–polymer micelles to overcome multi-drug resistance. Biomaterials 32:9444–56 [Google Scholar]
  127. Suzawa T, Nagamura S, Saito H, Ohta S, Hanai N. 127.  et al. 2002. Enhanced tumor cell selectivity of adriamycin-monoclonal antibody conjugate via a poly(ethylene glycol)-based cleavable linker. J. Control. Release 79:229–42 [Google Scholar]
  128. Caldorera-Moore ME, Liechty WB, Peppas NA. 128.  2011. Responsive theranostic systems: integration of diagnostic imaging agents and responsive controlled release drug delivery carriers. Acc. Chem. Res. 44:1061–70 [Google Scholar]
  129. Hood JD, Bednarski M, Frausto R, Guccione S, Reisfeld RA. 129.  et al. 2002. Tumor regression by targeted gene delivery to the neovasculature. Science 296:2404–7 [Google Scholar]
  130. Chen QR, Zhang L, Gasper W, Mixson AJ. 130.  2001. Targeting tumor angiogenesis with gene therapy. Mol. Genet. Metabol. 74:120–27 [Google Scholar]
  131. Teicher BA.131.  2000. Molecular targets and cancer therapeutics: discovery, development and clinical validation. Drug Resist. Updates 3:67–73 [Google Scholar]
  132. Pardridge WM.132.  2005. The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14 [Google Scholar]
  133. Alley SC, Okeley NM, Senter PD. 133.  2010. Antibody–drug conjugates: targeted drug delivery for cancer. Curr. Opin. Chem. Biol. 14:529–37 [Google Scholar]
  134. Zhao X, Li H, Lee RJ. 134.  2008. Targeted drug delivery via folate receptors. Expert Opin. Drug Deliv. 5:309–19 [Google Scholar]
  135. Michaelis K, Hoffmann MM, Dreis S, Herbert E, Alyautdin RN. 135.  et al. 2006. Covalent linkage of apolipoprotein E to albumin nanoparticles strongly enhances drug transport into the brain. J. Pharmacol. Exp. Ther. 317:1246–53 [Google Scholar]
  136. Bansal A, Kapoor DN, Kapil R, Chhabra N, Dhawan S. 136.  2011. Design and development of paclitaxel-loaded bovine serum albumin nanoparticles for brain targeting. Acta Pharm. 61:141–56 [Google Scholar]
  137. Wong HL, Wu XY, Bendayan R. 137.  2012. Nanotechnological advances for the delivery of CNS therapeutics. Adv. Drug Deliv. Rev. 64:686–700 [Google Scholar]
  138. Wohlfart S, Khalansky AS, Gelperina S, Begley D, Kreuter J. 138.  2011. Kinetics of transport of doxorubicin bound to nanoparticles across the blood–brain barrier. J. Control. Release 154:103–7 [Google Scholar]
  139. Wohlfart S, Gelperina S, Kreuter J. 139.  2012. Transport of drugs across the blood–brain barrier by nanoparticles. J. Control. Release 161:264–73 [Google Scholar]
  140. Mallapragada SK, Brenza TM, McMillan JM, Narasimhan B, Sakaguchi DS. 140.  et al. 2015. Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines. Nanomedicine 11:715–29 [Google Scholar]
  141. Puligujja P, McMillan J, Kendrick L, Li T, Balkundi S. 141.  et al. 2013. Macrophage folate receptor–targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections. Nanomedicine 9:1263–73 [Google Scholar]
  142. Kanmogne GD, Singh S, Roy U, Liu X, McMillan J. 142.  et al. 2012. Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells. Int. J. Nanomed. 7:2373–88 [Google Scholar]
  143. Wu D, Pardridge WM. 143.  1998. Pharmacokinetics and blood–brain barrier transport of an anti-transferrin receptor monoclonal antibody (OX26) in rats after chronic treatment with the antibody. Drug Metabol. Dispos. 26:937–39 [Google Scholar]
  144. Wong HL, Wu XY, Bendayan R. 144.  2012. Nanotechnological advances for the delivery of CNS therapeutics. Adv. Drug Deliv. Rev. 64:686–700 [Google Scholar]
  145. Bechara C, Sagan S. 145.  2013. Cell-penetrating peptides: 20 years later, where do we stand. ? FEBS Lett. 587:1693–702 [Google Scholar]
  146. Shao K, Huang R, Li J, Han L, Ye L. 146.  et al. 2010. Angiopep-2 modified PE-PEG based polymeric micelles for amphotericin B delivery targeted to the brain. J. Control. Release 147:118–26 [Google Scholar]
  147. Shao K, Huang R, Li J, Han L, Ye L. 147.  et al. 2010. Angiopep-2 modified PE-PEG based polymeric micelles for amphotericin B delivery targeted to the brain. J. Control. Release 147:118–26 [Google Scholar]
  148. Ke W, Shao K, Huang R, Han L, Liu Y. 148.  et al. 2009. Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials 30:6976–85 [Google Scholar]
  149. Xin H, Sha X, Jiang X, Chen L, Law K. 149.  et al. 2012. The brain targeting mechanism of Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles. Biomaterials 33:1673–81 [Google Scholar]
  150. Jin H, Kanthasamy A, Ghosh A, Anantharam V, Kalyanaraman B, Kanthasamy AG. 150.  2014. Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim. Biophys. Acta 1842:1282–94 [Google Scholar]
  151. Allen TM, Cullis PR. 151.  2004. Drug delivery systems: entering the mainstream. Science 303:1818–22 [Google Scholar]
  152. Vela Ramirez JE, Roychoudhury R, Habte HH, Cho MW, Pohl NL, Narasimhan B. 152.  2014. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells. J. Biomater. Sci. 25:1387–406 [Google Scholar]
  153. Ross KA, Loyd H, Wu W, Huntimer L, Wannemuehler MJ. 153.  et al. 2014. Structural and antigenic stability of H5N1 hemagglutinin trimer upon release from polyanhydride nanoparticles. J. Biomed. Mater. Res. A 102:4161–68 [Google Scholar]
  154. Haughney SL, Petersen LK, Schoofs AD, Ramer-Tait AE, King JD. 154.  et al. 2013. Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles. Acta Biomater. 9:8262–71 [Google Scholar]
  155. Petersen LK, Sackett CK, Narasimhan B. 155.  2010. High-throughput analysis of protein stability in polyanhydride nanoparticles. Acta Biomater. 6:3873–81 [Google Scholar]
  156. Hua Z, Hou B. 156.  2013. TLR signaling in B-cell development and activation. Cell. Mol. Immunol. 10:103–6 [Google Scholar]
  157. Plattner F, Yarovinsky F, Romero S, Didry D, Carlier MF. 157.  et al. 2008. Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. Cell Host Microbe 3:77–87 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error