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Nano delivery systems and cancer immunotherapy

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Abstract

Cancer immunotherapy takes advantage of immune system to fight against cancer. Current clinical immunotherapies are based on the administration of immune checkpoint inhibitors or immune modulators to reverse the immune suppression. Although robust and long-term tumor suppression is induced in “certain treated population”, single immunotherapy still suffers from limited efficacy in clinic. Combination with nanomedicine would be one of major strategies that can widen the effective patient populations and reduce side effects. The basis in combining nanomedicine and immunotherapy stems from the close relationship of tumor and immune system. Depending on the therapeutic cargo, nanocarriers can not only facilitate stronger innate or adaptive immunity but also reverse of immunosuppression. In the other hand, nanotechnology can potentiate the efficacy of immunotherapy by enhancing the delivery, retention and narrow the toxicity of immunomodulators. The strategies and rationales of nanocarrier design in the context of cancer immunotherapy are discussed in this review.

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References

  • Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Röhl I, Hopfner KP, Ludwig J, Hornung V (2013) CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498:380–384

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Acquavella N, Kluger H, Rhee J, Farber L, Tara H, Ariyan S, Narayan D, Kelly W, Sznol M (2008) Toxicity and activity of a twice daily high-dose bolus interleukin 2 regimen in patients with metastatic melanoma and metastatic renal cell cancer. J Immunother 31:569–576

    Article  PubMed  CAS  Google Scholar 

  • Agostinis P, Berg K, Cengel K, Foster T, Girotti A, Gollnick S, Hahn S, Hamblin M, Juzeniene A, Kessel D, Koberlik M, Moan J, Mroz P, Nowis D, Piette J, Wilson B, Golab J (2011) Photodynamic therapy of cancer: an update. CA Cancer J Clin 61:250–281

    Article  PubMed  PubMed Central  Google Scholar 

  • Alander JT, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin VV, Venermo M, Välisuo P (2012) A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012:940585

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Appelbe OK, Moynihan KD, Flor A, Rymut N, Irvine DJ, Kron SJ (2017) Radiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide. J Control Release 266:248–255

    Article  PubMed  CAS  Google Scholar 

  • Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, Tran T, Guerin CL, Chauvat A, Dransart E, Alanio C, Albert S et al (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-Associated head and neck cancer. Cancer Res 73:128–138

    Article  PubMed  CAS  Google Scholar 

  • Bhatia S, Tykodi SS, Thompson JA (2009) Treatment of metastatic melanoma: an overview. Oncology (Williston Park) 23:488–496

    Google Scholar 

  • Bringmann A, Held SAE, Heine A, Brossart P (2010) RNA vaccines in cancer treatment. J Biomed Biotechnol 2010:623687

  • Cano-Mejia J, Burga RA, Sweeney EE, Fisher JP, Bollard CM, Sandler AD, Cruz CRY, Fernandes R (2017) Prussian blue nanoparticle-based photothermal therapy combined with checkpoint inhibition for photothermal immunotherapy of neuroblastoma. Nanomed Nanotechnol Biol Med 13:771–781

    Article  CAS  Google Scholar 

  • Casares N, Pequignot MO, Tesniere A, Ghiringhelli F, Roux S, Chaput N, Schmitt E, Hamai A, Hervas-Stubbs S, Obeid M, Coutant F, Métivier D, Pichard E, Aucouturier P, Pierron G, Garrido C, Zitvogel L, Kroemer G (2005) Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202:1691–1701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z (2016a) Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun 7:1–13

    Google Scholar 

  • Chen Y, Xia R, Huang Y, Zhao W, Li J, Zhang X, Wang P, Venkataramanan R, Fan J, Xie W, Ma X, Lu B, Li S (2016b) An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat Commun 7:13443

    Article  PubMed  CAS  Google Scholar 

  • Claesson MH (2009) Why current peptide-based cancer vaccines fail: lessons from the three Es. Immunotherapy 1:513–516

    PubMed  Google Scholar 

  • Connolly DJ, O’Neill LA (2012) New developments in Toll-like receptor targeted therapeutics. Curr Opin Pharmacol 12:510–518

    Article  PubMed  CAS  Google Scholar 

  • Diner EJ, Burdette DL, Wilson SC, Monroe KM, Kellenberger CA, Hyodo M, Hayakawa Y, Hammond MC, Vance RE (2013) The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep 3:1355–1361

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fourcade J, Sun Z, Pagliano O, Chauvin JM, Sander C, Janjic B, Tarhini AA, Tawbi HA, Kirkwood JM, Moschos S, Wang H, Guillaume P, Luescher IF, Krieg A, Anderson AC, Kuchroo VK, Zarour HM (2014) PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8+ T cells induced by melanoma vaccines. Cancer Res 74:1045–1055

    Article  PubMed  CAS  Google Scholar 

  • Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S (2005) Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 353:38–52

    Article  PubMed  CAS  Google Scholar 

  • Guo X, You J (2017) Near infrared light-controlled therapeutic molecules release of nanocarriers in cancer therapy. J Pharm Investig 47:297–316

    Article  CAS  Google Scholar 

  • Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang X-Y (2013) Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res 119:421–475

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • He C, Duan X, Guo N, Chan C, Poon C, Weichselbaum RR, Lin W (2016) Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat Commun 7:1–12

    Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJM, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hong SH, Choi Y (2018) Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents. J Pharm Investig 48:3–17

    Article  CAS  Google Scholar 

  • Hwang HS, Shin H, Han J, Na K (2018) Combination of photodynamic therapy (PDT) and anti-tumor immunity in cancer therapy. J Pharm Investig 48:143–151

    Article  CAS  Google Scholar 

  • Jenkins RW, Barbie DA, Flaherty KT (2018) Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 118:9–16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jiang X, Zhou J, Giobbie-Hurder A, Wargo J, Hodi FS (2013) The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res 19:598–609

    Article  PubMed  CAS  Google Scholar 

  • Kong M, Tang J, Qiao Q, Wu T, Qi Y, Tan S, Gao X, Zhang Z (2017) Biodegradable hollow mesoporous silica nanoparticles for regulating tumor microenvironment and enhancing antitumor efficiency. Theranostics 7:3276–3292

    Article  PubMed  PubMed Central  Google Scholar 

  • Krieg AM (2006) Therapeutic potential of toll-like receptor 9 activation. Nat Rev Drug Discov 5:471–484

    Article  PubMed  CAS  Google Scholar 

  • Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72

    Article  PubMed  CAS  Google Scholar 

  • Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ (2016) Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater 16:489–496

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kulkarni A, Natarajan SK, Chandrasekar V, Pandey PR, Sengupta S (2016) Combining immune checkpoint inhibitors and kinase-inhibiting supramolecular therapeutics for enhanced anticancer efficacy. ACS Nano 10:9227–9242

    Article  CAS  Google Scholar 

  • Lakshminarayanan V, Thompson P, Wolfert MA, Buskas T, Bradley JM, Pathangey LB, Madsen CS, Cohen PA, Gendler SJ, Boons G-J (2012) Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc Natl Acad Sci 109:261–266

    Article  PubMed  Google Scholar 

  • Li L, Yang S, Song L, Zeng Y, Gong C (2018) An endogenous vaccine based on fluorophores and multivalent immunoadjuvants regulates tumor micro-environment for synergistic photothermal and immunotherapy. Theranostics 8:860–873

    Article  PubMed  PubMed Central  Google Scholar 

  • Lipson EJ, Forde PM, Hammers HJ, Emens LA, Taube JM, Topalian SL (2015) Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol 42:587–600

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Y, Qiao L, Zhang S, Wan G, Chen B, Zhou P, Zhang N, Wang Y (2017) Dual pH-responsive multifunctional nanoparticles for targeted treatment of breast cancer by combining immunotherapy and chemotherapy. Acta Biomater 66:310–324

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Wang Y, Miao L, Liu Q, Musetti S, Li J, Huang L (2018) Combination immunotherapy of MUC1 mRNA nano-vaccine and CTLA-4 blockade effectively inhibits growth of triple negative breast cancer. Mol Ther 26:45–55

    Article  PubMed  CAS  Google Scholar 

  • Lu K, He C, Guo N, Chan C, Ni K, Weichselbaum RR, Lin W (2016) Chlorin-based nanoscale metal–organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy. J Am Chem Soc 138:12502–12510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu J, Liu X, Liao YP, Salazar F, Sun B, Jiang W, Chang CH, Jiang J, Wang X, Wu AM, Meng H, Nel AE (2017) Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression. Nat Commun 8:1811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luo M, Wang H, Wang Z, Cai H, Lu Z, Li Y, Du M, Huang G, Wang C, Chen X, Porembka MR, Lea J, Frankel AE, Fu YX, Chen ZJ, Gao J (2017) A STING-activating nanovaccine for cancer immunotherapy. Nat Nanotechnol 12:648–654

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, Lush RM, Antonia S, Gabrilovich DI (2006) All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66:9299–9307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, Chawla A, Curran M, Hwu P, Sharma P, Litton JK, Molldrem JJ, Alatrash G (2014) PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2:361–370

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Munn DH, Mellor AL (2016) IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol 37:193–207

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Neill LAJ, Golenbock D, Bowie AG (2013) The history of Toll-like receptors-redefining innate immunity. Nat Rev Immunol 13:453–460

    Article  PubMed  CAS  Google Scholar 

  • Palucka AK, Coussens LM (2016) The basis of oncoimmunology. Cell 164:1233–1247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park J, Wrzesinski SH, Stern E, Look M, Criscione J, Ragheb R, Jay SM, Demento SL, Agawu A, Licona Limon P, Ferrandino AF, Gonzalez D, Habermann A, Flavell RA, Fahmy TM (2012) Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat Mater 11:895–905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park O, Yu G, Jung H, Mok H (2017) Recent studies on micro-/nano-sized biomaterials for cancer immunotherapy. J Pharm Investig 47:11–18

    Article  CAS  Google Scholar 

  • Pfirschke C, Engblom C, Rickelt S, Cortez-Retamozo V, Garris C, Pucci F, Yamazaki T, Poirier-Colame V, Newton A, Redouane Y, Lin YJ, Wojtkiewicz G, Iwamoto Y, Mino-Kenudson M, Huynh TG, Hynes RO, Freeman GJ, Kroemer G, Zitvogel L et al (2016) Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity 44:343–354

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Seth A, Lee H, Cho MY, Park C, Korm S, Lee J-Y, Choi I, Lim YT, Hong KS (2017) Combining vasculature disrupting agent and Toll-like receptor 7/8 agonist for cancer therapy. Oncotarget 8:5371–5381

    Article  PubMed  Google Scholar 

  • Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A (2017) Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168:707–723

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shim G, Kim MG, Park JY, Oh YK (2016) Graphene-based nanosheets for delivery of chemotherapeutics and biological drugs. Adv Drug Deliv Rev 105:205–227

    Article  PubMed  CAS  Google Scholar 

  • Shim G, Ko S, Kim D, Le QV, Park GT, Lee J, Kwon T, Choi HG, Kim YB, Oh YK (2017) Light-switchable systems for remotely controlled drug delivery. J Control Release 267:67–79

    Article  PubMed  CAS  Google Scholar 

  • Smits ELJM., Ponsaerts P, Berneman ZN, Van Tendeloo VFI (2008) The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 13:859–875

    Article  PubMed  CAS  Google Scholar 

  • Sonpavde G (2017) PD-1 and PD-L1 inhibitors as salvage therapy for urothelial carcinoma. N Engl J Med 376:1073–1074

    Article  PubMed  Google Scholar 

  • Sun J, Chen Y, Huang Y, Zhao W, Liu Y, Venkataramanan R, Lu B, Li S (2017) Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier. Acta Pharmacol Sin 38:823

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tao Y, Ju E, Ren J, Qu X (2014) Immunostimulatory oligonucleotides-loaded cationic graphene oxide with photothermally enhanced immunogenicity for photothermal/immune cancer therapy. Biomaterials 35:9963–9971

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Ma R, Yan L, Chen X, Zhu G (2015) Combined chemotherapy and photodynamic therapy using a nanohybrid based on layered double hydroxides to conquer cisplatin resistance. Chem Commun 51:11587–11590

    Article  CAS  Google Scholar 

  • Wang C, Sun W, Wright G, Wang AZ, Gu Z (2016a) Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and anti-PD1 antibody. Adv Mater 28:8912–8920

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang D, Wang T, Liu J, Yu H, Jiao S, Feng B, Zhou F, Fu Y, Yin Q, Zhang P, Zhang Z, Zhou Z, Li Y (2016b) Acid-activatable versatile micelleplexes for PD-L1 blockade-enhanced cancer photodynamic immunotherapy. Nano Lett 16:5503–5513

    Article  PubMed  CAS  Google Scholar 

  • Wang N, Wang Z, Xu Z, Chen X, Zhu G (2018) A cisplatin-loaded immuno-chemotherapeutic nanohybrid bearing immune checkpoint inhibitors for enhanced cervical cancer therapy. Angew Chemie Int Ed. https://doi.org/10.1002/anie.201800422

    Article  Google Scholar 

  • Wilson DR, Sen R, Sunshine JC, Pardoll DM, Green JJ, Kim YJ (2018) Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy. Nanomed Nanotechnol Biol Med 14:237–246

    Article  CAS  Google Scholar 

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon R-A, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE et al (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MYK, Duggan R, Wang Y, Barber GN, Fitzgerald KA, Alegre ML, Gajewski TF (2014) STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:830–842

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wrzesinski SH, Wan YY, Flavell RA (2007) Transforming growth factor-β and the immune response: Implications for anticancer therapy. Clin Cancer Res 13:5262–5270

    Article  PubMed  CAS  Google Scholar 

  • Wu MX, Yang YW (2017) Metal–organic framework (MOF)-based drug/cargo delivery and cancer therapy. Adv Mater 29:1–20

    Google Scholar 

  • Yang G, Xu L, Chao Y, Xu J, Sun X, Wu Y, Peng R, Liu Z (2017) Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat Commun 8:902

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhai L, Ladomersky E, Lenzen A, Nguyen B, Patel R, Lauing KL, Wu M, Wainwright DA (2018) IDO1 in cancer: a Gemini of immune checkpoints. Cell Mol Immunol 15:1–11

    Article  CAS  Google Scholar 

  • Zhang M, Zhang Z, Blessington D, Li H, Busch TM, Madrak V, Miles J, Chance B, Glickson JD, Zheng G (2003) Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters. Bioconjug Chem 14:709–714

    Article  PubMed  CAS  Google Scholar 

  • Zhao L, Seth A, Wibowo N, Zhao CX, Mitter N, Yu C, Middelberg APJ (2014) Nanoparticle vaccines. Vaccine 32:327–337

    Article  PubMed  Google Scholar 

  • Zhou F, Nordquist RE, Chen WR (2016) Photonics immunotherapy—a novel strategy for cancer treatment. J Innov Opt Health Sci 9:1–11

    Article  CAS  Google Scholar 

  • Zhu G, Lynn GM, Jacobson O, Chen K, Liu Y, Zhang H, Ma Y, Zhang F, Tian R, Ni Q, Cheng S, Wang Z, Lu N, Yung BC, Wang Z, Lang L, Fu X, Jin A, Weiss ID et al (2017) Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy. Nat Commun 8:1954

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715–727

    Article  PubMed  CAS  Google Scholar 

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Funding

This study was funded by research grants from the Ministry of Science and Future Planning, Republic of Korea (NRF-2018R1A2A1A05019203), and the Korean Health Technology R&D Project (No. HI15C2842), Ministry of Health & Welfare, Republic of Korea.

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Correspondence to Yu-Kyoung Oh.

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These authors (Q.-V. Le, J. Choi, and Y.K. Oh) declare that there is no conflict of interest.

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This article does not contain any studies with human and animal subjects performed by any of the authors.

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Le, QV., Choi, J. & Oh, YK. Nano delivery systems and cancer immunotherapy. J. Pharm. Investig. 48, 527–539 (2018). https://doi.org/10.1007/s40005-018-0399-z

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