Skip to main content
SpringerLink
Log in

Recent progress in dendrimer-based nanomedicine development

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural properties of dendrimers have created many applications for drug and gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers are not only capable of delivering drugs or diagnostic agents to desired sites by encapsulating or conjugating them to the periphery, but also have therapeutic efficacy in their own. When compared to traditional polymers for drug delivery, dendrimers have distinct advantages, such as high drug-loading capacity at the surface terminal for conjugation or interior space for encapsulation, size control with well-defined numbers of peripheries, and multivalency for conjugation to drugs, targeting moieties, molecular sensors, and biopolymers. This review focuses on recent applications of dendrimers for the development of dendrimer-based nanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still face some challenges including scale-up production and well-characterization, several dendrimer-based drug candidates are expected to enter clinical development phase in the near future.

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

  • Abdoli A, Radmehr N, Bolhassani A, Eidi A, Mehrbod P, Motevalli F, Kianmehr Z, Chiani M, Mahdavi M, Yazdani S, Ardestani MS, Kandi MR, Aghasadeghi MR (2017) Conjugated anionic PEG-citrate G2 dendrimer with multi-epitopic HIV-1 vaccine candidate enhance the cellular immune responses in mice. Artif Cells Nanomed Biotechnol 45:1762–1768

    Article  PubMed  CAS  Google Scholar 

  • Akhtar S, Al-Zaid B, El-Hashim AZ, Chandrasekhar B, Attur S, Benter IF (2016) Impact of PAMAM delivery systems on signal transduction pathways in vivo: modulation of ERK1/2 and p38 MAP kinase signaling in the normal and diabetic kidney. Int J Pharm 514:353–363

    Article  PubMed  CAS  Google Scholar 

  • Alarcón GS (2000) Methotrexate use in rheumatoid arthritis. A Clinician’s perspective. Immunopharmacology 47:259–271

    Article  PubMed  Google Scholar 

  • Avila-Salas F, Sandoval C, Caballero J, Guiñez-Molinos S, Santos LS, Cachau RE, González-Nilo FD (2012) Study of interaction energies between the PAMAM dendrimer and nonsteroidal anti-inflammatory drug using a distributed computational strategy and experimental analysis by ESI-MS/MS. J Phys Chem B 116:2031–2039

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bahadoran A, Ebrahimi M, Yeap SK, Safi N, Moeini H, Hair-Bejo M, Hussein MZ, Omar AR (2017) Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model. Int J Nanomedcine 12:8573–8585

    Article  Google Scholar 

  • Barth RF, Adams DM, Soloway AH, Alam F, Darby MV (1994) Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. Bioconjug Chem 5:58–66

    Article  PubMed  CAS  Google Scholar 

  • Barth RF, Coderre JA, Vicente MG, Blue TE (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002

    Article  PubMed  CAS  Google Scholar 

  • Barth RF, Wu G, Meisen WH, Nakkula RJ, Yang W, Huo T, Kellough DA, Kaumaya P, Turro C, Agius LM, Kaur B (2016) Design, synthesis, and evaluation of cisplatin-containing EGFR targeting bioconjugates as potential therapeutic agents for brain tumors. Onco Targets Ther 9:2769–2781

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bernstein DI, Stanberry LR, Sacks S, Ayisi NK, Gong YH, Ireland J, Mumper RJ, Holan G, Matthews B, McCarthy T, Bourne N (2003) Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes. Antimicrob Agents Chemother 47:3784–3788

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bhatia S, Camacho LC, Haag R (2016) Pathogen inhibition by multivalent ligand architectures. J Am Chem Soc 138:8654–8666

    Article  PubMed  CAS  Google Scholar 

  • Boas U, Heegaard PM (2004) Dendrimers in drug research. Chem Soc Rev 33:43–63

    Article  PubMed  CAS  Google Scholar 

  • Bosch X (2011) Dendrimers to treat rheumatoid arthritis. ACS Nano 5:6779–6785

    Article  PubMed  CAS  Google Scholar 

  • Bourne N, Stanberry LR, Kern ER, Holan G, Matthews B, Bernstein DI (2000) Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother 44:2471–2474

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Calixto GM, Bernegossi J, de Freitas LM, Fontana CR, Chorilli M (2016) Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: a review. Molecules 21:342

    Article  PubMed  CAS  Google Scholar 

  • Capala J, Barth RF, Bendayan M, Lauzon M, Adams DM, Soloway AH, Fenstermaker RA, Carlsson J (1996) Boronated epidermal growth factor as a potential targeting agent for boron neutron capture therapy of brain tumors. Bioconjug Chem 7:7–15

    Article  PubMed  CAS  Google Scholar 

  • Caster JM, Patel AN, Zhang T, Wang A (2017) Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. WIREs Nanomed Nanobiotechnol 9:e1416

    Article  Google Scholar 

  • Chang Y, Meng X, Zhao Y, Li K, Zhao B, Zhu M, Li Y, Chen X, Wang J (2011) Novel water-soluble and pH-responsive anticancer drug nanocarriers: doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs). J Colloid Interface Sci 363:403–409

    Article  PubMed  CAS  Google Scholar 

  • Chauhan AS, Diwan PV, Jain NK, Tomalia DA (2009) Unexpected in vivo anti-inflammatory activity observed for simple, surface functionalized poly(amidoamine) dendrimers. Biomacromol 10:1195–1202

    Article  CAS  Google Scholar 

  • Chen CZ, Cooper SL (2002) Interactions between dendrimer biocides and bacterial membranes. Biomaterials 23:3359–3368

    Article  PubMed  CAS  Google Scholar 

  • Choi SK, Myc A, Silpe JE, Sumit M, Wong PT, McCarthy K, Desai AM, Thomas TP, Kotlyar A, Holl MM, Orr BG, Baker JR Jr (2013) Dendrimer-based multivalent vancomycin nanoplatform for targeting the drug-resistant bacterial surface. ACS Nano 7:214–228

    Article  PubMed  CAS  Google Scholar 

  • Choi JY, Thapa RK, Yong CS, Kim JO (2016) Nanoparticle-based combination drug delivery systems for synergistic cancer treatment. J Pharm Investig 46:325–339

    Article  CAS  Google Scholar 

  • Chouai A, Venditto VJ, Simanek EE, Vanderplas BC, Ragan JA (2009) Large scale, green synthesis of a genenration-1 melamine (trazine) dendrimer. Organic Synth 86:151–160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Davignon JL, Hayder M, Baron M, Boyer JF, Constantin A, Apparailly F, Poupot R, Cantagrel A (2013) Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology 52:590–598

    Article  PubMed  CAS  Google Scholar 

  • Duncan R, Izzo L (2005) Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 57:2215–2237

    Article  PubMed  CAS  Google Scholar 

  • Durocher I, Girard D (2016) In vivo proinflammatory activity of generations 0–3 (G0-G3) polyamidoamine (PAMAM) nanoparticles. Inflamm Res 65:745–755

    Article  PubMed  CAS  Google Scholar 

  • Esfand R, Tomalia DA (2001) Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6:427–436

    Article  PubMed  CAS  Google Scholar 

  • Gajbhiye V, Palanirajan VK, Tekade RK, Jain NK (2009) Dendrimers as therapeutic agents: a systematic review. J Pharm Pharmacol 61:989–1003

    Article  PubMed  CAS  Google Scholar 

  • Gong Y, Matthews B, Cheung D, Tam T, Gadawski I, Leung D, Holan G, Raff J, Sacks S (2002) Evidence of dual sites of action of dendrimers: SPL-2999 inhibits both virus entry and late stages of herpes simplex virus replication. Antiviral Res 55:319–329

    Article  PubMed  CAS  Google Scholar 

  • Gupta U, Agashe HB, Asthana A, Jain NK (2006) Dendrimers: novel polymeric nanoarchitectures for solubility enhancement. Biomacromol 7:649–658

    Article  CAS  Google Scholar 

  • Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8:533–544

    Article  PubMed  CAS  Google Scholar 

  • Hayden F (2009) Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis 48:S3–S13

    Article  PubMed  CAS  Google Scholar 

  • Hayder M, Poupot M, Baron M, Nigon D, Turrin CO, Caminade AM, Majoral JP, Eisenberg RA, Fournié JJ, Cantagrel A, Poupot R, Davignon JL (2011) A phosphorus-based dendrimer targets inflammation and osteoclastogenesis in experimental arthritis. Sci Transl Med 3:81ra35

  • He H, Li Y, Jia XR, Du J, Ying X, Lu WL, Lou JN, Wei Y (2011) PEGylated poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials 32:478–487

    Article  PubMed  CAS  Google Scholar 

  • Hoang NH, Lim C, Sim T, Oh KT (2017) Triblock copolymers for nano-sized drug delivery systems. J Pharm Investig 47:27–35

    Article  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 

  • Hu J, Su Y, Zhang H, Xu T, Cheng Y (2011) Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery. Biomaterials 32:9950–9959

    Article  PubMed  CAS  Google Scholar 

  • Huang B, Desai A, Zong H, Tang S, Leroueil P, Baker JR Jr (2011) Copper-free click conjugation of methotrexate to a PAMAM dendrimer platform. Tetrahedron Lett 52:1411–1414

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jain K, Kesharwani P, Gupta U, Jain NK (2010) Dendrimer toxicity: let’s meet the challenge. Int J Pharm 394:122–142

    Article  PubMed  CAS  Google Scholar 

  • Jain NK, Tare MS, Mishra V, Tripathi PK (2015) The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel. Nanomedicine 11:207–218

    Article  PubMed  CAS  Google Scholar 

  • Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB, D’Emanuele A (2003) The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm 252:263–266

    Article  PubMed  CAS  Google Scholar 

  • Jin Y, Ren X, Wang W, Ke L, Ning E, Du L, Bradshaw J (2011) A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting. Int J Pharm 420:378–384

    Article  PubMed  CAS  Google Scholar 

  • Kambhampati SP, Mishra MK, Mastorakos P, Oh Y, Lutty GA, Kannan RM (2015) Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells. Eur J Pharm Biopharm 95:239–249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaminskas LM, Kelly BD, McLeod VM, Boyd BJ, Krippner GY, Williams ED, Porter CJ (2009) Pharmacokinetics and tumor disposition of PEGylated, methotrexate conjugated poly-l-lysine dendrimers. Mol Pharm 6:1190–1204

    Article  PubMed  CAS  Google Scholar 

  • Kaminskas LM, McLeod VM, Porter CJ, Boyd BJ (2012) Association of chemotherapeutic drugs with dendrimer nanocarriers: an assessment of the merits of covalent conjugation compared to noncovalent encapsulation. Mol Pharm 9:355–373

    Article  PubMed  CAS  Google Scholar 

  • Kaminskas LM, McLeod VM, Ascher DB, Ryan GM, Jones S, Haynes JM, Trevaskis NL, Chan LJ, Sloan EK, Finnin BA, Williamson M, Velkov T, Williams ED, Kelly BD, Owen DJ, Porter CJ (2015) Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats. Mol Pharm 12:432–443

    Article  PubMed  CAS  Google Scholar 

  • Kannan RM, Nance E, Kannan S, Tomalia DA (2014) Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med 276:579–617

    Article  PubMed  CAS  Google Scholar 

  • Kesavan A, Ilaiyaraja P, Sofi Beaula W, Veena Kumari V, Sugin Lal J, Arunkumar C, Anjana G, Srinivas S, Ramesh A, Rayala SK, Ponraju D, Venkatraman G (2015) Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin. Eur J Pharm Biopharm 96:255–263

    Article  PubMed  CAS  Google Scholar 

  • Kesharwani P, Iyer AK (2015) Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discov Today 20:536–547

    Article  PubMed  CAS  Google Scholar 

  • Khatri S, Das NG, Das SK (2014) Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells. J Pharm Bioallied Sci 6:297–302

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim Y, Klutz AM, Jacobson KA (2008) Systematic investigation of polyamidoamine dendrimers surface-modified with poly(ethylene glycol) for drug delivery applications: synthesis, characterization, and evaluation of cytotoxicity. Bioconjug Chem 19:1660–1672

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim Y, Park EJ, Na DH (2016) Antibody-drug conjugates for targeted anticancer drug delivery. J Pharm Investig 46:341–349

    Article  CAS  Google Scholar 

  • Kim CH, Lee SG, Kang MJ, Lee S, Choi YW (2017) Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting. J Pharm Investig 47:203–227

    Article  CAS  Google Scholar 

  • Kirkpatrick GJ, Plumb JA, Sutcliffe OB, Flint DJ, Wheate NJ (2011) Evaluation of anionic half generation 3.5-6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin. J Inorg Biochem 105:1115–1122

    Article  PubMed  CAS  Google Scholar 

  • Klajnert B, Bryszewska M (2001) Dendrimers: properties and applications. Acta Biochim Pol 48:199–208

    PubMed  CAS  Google Scholar 

  • Klajnert B, Rozanek M, Bryszewska M (2012) Dendrimers in photodynamic therapy. Curr Med Chem 19:4903–4912

    Article  PubMed  CAS  Google Scholar 

  • Koç FE, Senel M (2013) Solubility enhancement of non-steroidal anti-inflammatory drugs (NSAIDs) using polypolypropylene oxide core PAMAM dendrimers. Int J Pharm 451:18–22

    Article  PubMed  CAS  Google Scholar 

  • Kojima C, Regino C, Umeda Y, Kobayashi H, Kono K (2010) Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers. Int J Pharm 383:293–296

    Article  PubMed  CAS  Google Scholar 

  • Kulhari H, Pooja D, Singh MK, Chauhan AS (2015) Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation. Drug Dev Ind Pharm 41:232–238

    Article  PubMed  CAS  Google Scholar 

  • Kurtoglu YE, Navath RS, Wang B, Kannan S, Romero R, Kannan RM (2009) Poly(amidoamine) dendrimer–drug conjugates with disulfide linkages for intracellular drug delivery. Biomaterials 30:2112–2121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kwon SJ, Na DH, Kwak JH, Douaisi M, Zhang F, Park EJ, Park JH, Youn H, Song CS, Kane RS, Dordick JS, Lee KB, Linhardt RJ (2017) Nanostructured glycan architecture is important in the inhibition of influenza A virus infection. Nat Nanotechnol 12:48–54

    Article  PubMed  CAS  Google Scholar 

  • Ladd E, Sheikhi A, Li N, van de Ven TGM, Kakkar A (2017) Design and synthesis of dendrimers with facile surface group functionalization, and an evaluation of their bactericidal efficacy. Molecules 22:868

    Article  CAS  Google Scholar 

  • Landarani-Isfahani A, Moghadam M, Mohammadi S, Royvaran M, Moshtael-Arani N, Rezaei S, Tangestaninejad S, Mirkhani V, Mohammadpoor-Baltork I (2017) Elegant pH-responsive nanovehicle for drug delivery based on triazine dendrimer modified magnetic nanoparticles. Langmuir 33:8503–8515

    Article  PubMed  CAS  Google Scholar 

  • Landers JJ, Cao Z, Lee I, Piehler LT, Myc PP, Myc A, Hamouda T, Galecki AT, Baker JR Jr (2002) Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers. J Infect Dis 186:1222–1230

    Article  PubMed  CAS  Google Scholar 

  • Lee CC, MacKay JA, Fréchet JM, Szoka FC (2005) Designing dendrimers for biological applications. Nat Biotechnol 23:1517–1526

    Article  PubMed  CAS  Google Scholar 

  • Lei J, Rosenzweig JM, Mishra MK, Alshehri W, Brancusi F, McLane M, Almalki A, Bahabry R, Arif H, Rozzah R, Alyousif G, Shabi Y, Alhehaily N, Zhong W, Facciabene A, Kannan S, Kannan RM, Burd I (2017) Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury. Sci Rep 7:6106

    Article  PubMed  PubMed Central  Google Scholar 

  • Leiro V, Garcia JP, Tomás H, Pêgo AP (2015) The present and the future of degradable dendrimers and derivatives in theranostics. Bioconjug Chem 26:1182–1197

    Article  PubMed  CAS  Google Scholar 

  • Li Y, He H, Jia X, Lu WL, Lou J, Wei Y (2012) A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials 33:3899–3908

    Article  PubMed  CAS  Google Scholar 

  • Li N, Cai H, Jiang L, Hu J, Bains A, Hu J, Gong Q, Luo K, Gu Z (2017a) Enzyme-sensitive and amphiphilic PEGylated dendrimer-paclitaxel prodrug-based nanoparticles for enhanced stability and anticancer efficacy. ACS Appl Mater Interfaces 9:6865–6877

    Article  PubMed  CAS  Google Scholar 

  • Li Y, He H, Lu W, Jia X (2017b) A poly(amidoamine) dendrimer-based drug carrier for delivering DOX to gliomas cells. RSC Adv 7:15475–15481

    Article  CAS  Google Scholar 

  • Lim LY, Koh PY, Somani S, Al Robaian M, Karim R, Yean YL, Mitchell J, Tate RJ, Edrada-Ebel R, Blatchford DR, Mullin M, Dufès C (2015) Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. Nanomedicine 11:1445–1454

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ly TU, Tran NQ, Hoang TK, Phan KN, Truong HN, Nguyen CK (2013) Pegylated dendrimer and its effect in fluorouracil loading and release for enhancing antitumor activity. J Biomed Nanotechnol 9:213–220

    Article  PubMed  CAS  Google Scholar 

  • Ma P, Zhang X, Ni L, Li J, Zhang F, Wang Z, Lian S, Sun K (2015) Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab. Int J Nanomedcine 10:2173–2190

    Article  CAS  Google Scholar 

  • Maeda H (2017) Polymer therapeutics and the EPR effect. J Drug Target 25:781–785

    Article  PubMed  CAS  Google Scholar 

  • Mastorakos P, Kambhampati SP, Mishra MK, Wu T, Song E, Hanes J, Kannan RM (2015) Hydroxyl PAMAM dendrimer-based gene vectors for transgene delivery to human retinal pigment epithelial cells. Nanoscale 7:3845–3856

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matai I, Sachdev A, Gopinath P (2015) Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells. Biomater Sci 3:457–468

    Article  PubMed  CAS  Google Scholar 

  • McCarthy TD, Karellas P, Henderson SA, Giannis M, O’Keefe DF, Heery G, Paull JR, Matthews BR, Holan G (2005) Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention. Mol Pharm 2:312–318

    Article  PubMed  CAS  Google Scholar 

  • Medina SH, El-Sayed ME (2009) Dendrimers as carriers for delivery of chemotherapeutic agents. Chem Rev 109:3141–3157

    Article  PubMed  CAS  Google Scholar 

  • Mehendale R, Joshi M, Patravale VB (2013) Nanomedicines for treatment of viral diseases. Crit Rev Ther Drug Carrier Syst 30:1–49

    Article  PubMed  CAS  Google Scholar 

  • Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15:171–185

    Article  PubMed  CAS  Google Scholar 

  • Michiue H, Sakurai Y, Kondo N, Kitamatsu M, Bin F, Nakajima K, Hirota Y, Kawabata S, Nishiki T, Ohmori I, Tomizawa K, Miyatake S, Ono K, Matsui H (2014) The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide. Biomaterials 35:3396–3405

    Article  PubMed  CAS  Google Scholar 

  • Mintzer MA, Dane EL, O’Toole GA, Grinstaff MW (2012) Exploiting dendrimer multivalency to combat emerging and re-emerging infectious diseases. Mol Pharm 9:342–354

    Article  PubMed  CAS  Google Scholar 

  • Nakamura Y, Mochida A, Choyke PL, Kobayashi H (2016) Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 27:2225–2238

    Article  PubMed  CAS  Google Scholar 

  • Nakashima-Matsushita N, Homma T, Yu S, Matsuda T, Sunahara N, Nakamura T, Tsukano M, Ratnam M, Matsuyama T (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616

    Article  PubMed  CAS  Google Scholar 

  • Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, Johnston MV, Rangaramanujam K, Blue ME, Kannan S (2017) Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome. J Neuroinflamm 14:252

    Article  Google Scholar 

  • Narsireddy A, Vijayashree K, Adimoolam MG, Manorama SV, Rao NM (2015) Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy. Int J Nanomedcine 10:6865–6878

    CAS  Google Scholar 

  • Navath RS, Kurtoglu YE, Wang B, Kannan S, Romero R, Kannan RM (2008) Dendrimer-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjug Chem 19:2446–2455

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Neibert K, Gosein V, Sharma A, Khan M, Whitehead MA, Maysinger D, Kakkar A (2013) “Click” dendrimers as anti-inflammatory agents: with insights into their binding from molecular modeling studies. Mol Pharm 10:2502–2508

    Article  PubMed  CAS  Google Scholar 

  • Park EJ, Na DH (2014) Palmitoylation of octreotide for incorporation into poly(amidoamine) dendrimers. J Pharm Investig 44:141–145

    Article  CAS  Google Scholar 

  • Park EJ, Na DH (2015) Difference in microchip electrophoretic mobility between partially and fully PEGylated poly(amidoamine) dendrimers. Anal Biochem 488:9–11

    Article  PubMed  CAS  Google Scholar 

  • Park EJ, Cho H, Kim SW, Na DH (2014) Chromatographic methods for characterization of poly(ethylene glycol)-modified polyamidoamine dendrimers. Anal Biochem 449:42–44

    Article  PubMed  CAS  Google Scholar 

  • Park EJ, Kim JE, Kim DK, Park JH, Lee KB, Na DH (2016) Glucosamine-conjugated anionic poly(amidoamine) dendrimers inhibit interleukin-8 production by Helicobacter pylori in gastric epithelial cells. Bull Korean Chem Soc 37:596–599

    Article  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 

  • Price CF, Tyssen D, Sonza S, Davie A, Evans S, Lewis GR, Xia S, Spelman T, Hodsman P, Moench TR, Humberstone A, Paull JR, Tachedjian G (2011) SPL7013 Gel (VivaGel®) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. PLoS One 6:e24095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qi R, Majoros I, Misra AC, Koch AE, Campbell P, Marotte H, Bergin IL, Cao Z, Goonewardena S, Morry J, Zhang S, Beer M, Makidon P, Kotlyar A, Thomas TP, Baker JR Jr (2015) Folate receptor-targeted dendrimer-methotrexate conjugate for inflammatory arthritis. J Biomed Nanotechnol 11:1431–1441

    Article  PubMed  CAS  Google Scholar 

  • Qi X, Qin J, Fan Y, Qin X, Jiang Y, Wu Z (2016) Carboxymethyl chitosan-modified polyamidoamine dendrimer enables progressive drug targeting of tumors via pH-sensitive charge inversion. J Biomed Nanotechnol 12:667–678

    Article  PubMed  CAS  Google Scholar 

  • Quintana A, Raczka E, Piehler L, Lee I, Myc A, Majoros I, Patri AK, Thomas T, Mulé J, Baker JR Jr (2002) Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res 19:1310–1316

    Article  PubMed  CAS  Google Scholar 

  • Reuter JD, Myc A, Hayes MM, Gan Z, Roy R, Qin D, Yin R, Piehler LT, Esfand R, Tomalia DA, Baker JR Jr (1999) Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers. Bioconjug Chem 10:271–278

    Article  PubMed  CAS  Google Scholar 

  • Ryan GM, McLeod VM, Mehta D, Kelly BD, Stanislawski PC, Owen DJ, Kaminskas LM, Porter CJH (2017) Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site. Nanomedicine 13:2485–2494

    Article  PubMed  CAS  Google Scholar 

  • Safavi MS, Shojaosadati SA, Yang HG, Kim Y, Park EJ, Lee KC, Na DH (2017) Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature. Int J Pharm 529:303–309

    Article  PubMed  CAS  Google Scholar 

  • Schumann C, Taratula O, Khalimonchuk O, Palmer AL, Cronk LM, Jones CV, Escalante CA, Taratula O (2015) ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression. Nanomedicine 11:1961–1970

    Article  PubMed  CAS  Google Scholar 

  • Sepúlveda-Crespo D, Gómez R, De La Mata FJ, Jiménez JL, Muñoz-Fernández MÁ (2015) Polyanionic carbosilane dendrimer-conjugated antiviral drugs as efficient microbicides: recent trends and developments in HIV treatment/therapy. Nanomedicine 11:1481–1498

    Article  PubMed  CAS  Google Scholar 

  • Sepúlveda-Crespo D, Ceña-Díez R, Jiménez JL, Ángeles Muñoz-Fernández M (2017) Mechanistic studies of viral entry: an overview of dendrimer-based microbicides as entry inhibitors against both HIV and HSV-2 overlapped infections. Med Res Rev 37:149–179

    Article  PubMed  CAS  Google Scholar 

  • Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U (2017) Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery. Drug Discov Today 22:314–326

    Article  PubMed  CAS  Google Scholar 

  • Shaunak S (2015) Perspective: dendrimer drugs for infection and inflammation. Biochem Biophys Res Commun 468:435–441

    Article  PubMed  CAS  Google Scholar 

  • Shaunak S, Thomas S, Gianasi E, Godwin A, Jones E, Teo I, Mireskandari K, Luthert P, Duncan R, Patterson S, Khaw P, Brocchini S (2004) Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Nat Biotechnol 22:977–984

    Article  PubMed  CAS  Google Scholar 

  • Shcharbin D, Shcharbina N, Dzmitruk V, Pedziwiatr-Werbicka E, Ionov M, Mignani S, de la Mata FJ, Gómez R, Muñoz-Fernández MA, Majoral JP, Bryszewska M (2017) Dendrimer-protein interactions versus dendrimer-based nanomedicine. Colloids Surf B Biointerfaces 152:414–422

    Article  PubMed  CAS  Google Scholar 

  • Sim T, Lim C, Hoang NH, Joo H, Lee JW, Kim D, Lee ES, Youn YS, Kim JO, Oh KT (2016) Nanomedicines for oral administration based on diverse nanoplatform. J Pharm Investig 46:351–362

    Article  CAS  Google Scholar 

  • Singh P (2007) Dendrimers and their applications in immunoassays and clinical diagnostics. Biotechnol Appl Biochem 48:1–9

    Article  PubMed  CAS  Google Scholar 

  • Singh L, Kruger HG, Maguire GEM, Govender T, Parboosing R (2017) The role of nanotechnology in the treatment of viral infections. Ther Adv Infect Dis 4:105–131

    PubMed  PubMed Central  CAS  Google Scholar 

  • Sk UH, Kojima C (2015) Dendrimers for theranostic applications. Biomol Concepts 6:205–217

    Article  PubMed  CAS  Google Scholar 

  • Soler M, Mesa-Antunez P, Estevez MC, Ruiz-Sanchez AJ, Otte MA, Sepulveda B, Collado D, Mayorga C, Torres MJ, Perez-Inestrosa E, Lechuga LM (2015) Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis. Biosens Bioelectron 66:115–123

    Article  PubMed  CAS  Google Scholar 

  • Son S, Lim SM, Chae SY, Kim K, Park EJ, Lee KC, Na DH (2015) Mono-lithocholated exendin-4-loaded glycol chitosan nanoparticles with prolonged antidiabetic effects. Int J Pharm 495:81–86

    Article  PubMed  CAS  Google Scholar 

  • Soto-Castro D, Cruz-Morales JA, Apan MTR, Guadarrama P (2012) Solubilization and anticancer-activity enhancement of Methotrexate by novel dendrimeric nanodevices synthesized in one-step reaction. Bioorg Chem 41:13–21

    Article  PubMed  CAS  Google Scholar 

  • Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications—reflections on the field. Adv Drug Deliv Rev 57:2106–2129

    Article  PubMed  CAS  Google Scholar 

  • Teow HM, Zhou Z, Najlah M, Yusof SR, Abbott NJ, D’Emanuele A (2013) Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier. Int J Pharm 441:701–711

    Article  PubMed  CAS  Google Scholar 

  • Thomas TP, Majoros IJ, Kotlyar A, Kukowska-Latallo JF, Bielinska A, Myc A, Baker JR Jr (2005) Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J Med Chem 48:3729–3735

    Article  PubMed  CAS  Google Scholar 

  • Thomas TP, Goonewardena SN, Majoros IJ, Kotlyar A, Cao Z, Leroueil PR, Baker JR Jr (2011) Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheum 63:2671–2680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tomalia DA, Fréchet JM (2002) Discovery of dendrimers and dendritic polymers: a brief historical perspective. J Polym Sci Part A: Polym Chem 40:2719–2728

    Article  CAS  Google Scholar 

  • Wang Q, Li J, An S, Chen Y, Jiang C, Wang X (2015) Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer. Int J Nanomedcine 10:4479–4490

    Article  CAS  Google Scholar 

  • Wang J, He H, Cooper RC, Yang H (2017) In situ-forming polyamidoamine dendrimer hydrogels with tunable properties prepared via aza-michael addition reaction. ACS Appl Mater Interfaces 9:10494–10503

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wiley DC, Skehel JJ (1987) The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 56:365–394

    Article  PubMed  CAS  Google Scholar 

  • Witvrouw M, Fikkert V, Pluymers W, Matthews B, Mardel K, Schols D, Raff J, Debyser Z, De Clercq E, Holan G, Pannecouque C (2000) Polyanionic (i.e., polysulfonate) dendrimers can inhibit the replication of human immunodeficiency virus by interfering with both virus adsorption and later steps (reverse transcriptase/integrase) in the virus replicative cycle. Mol Pharmacol 58:1100–1108

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Barth RF, Yang W, Chatterjee M, Tjarks W, Ciesielski MJ, Fenstermaker RA (2004) Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy. Bioconjug Chem 15:185–194

    Article  PubMed  CAS  Google Scholar 

  • Wu LP, Ficker M, Christensen JB, Trohopoulos PN, Moghimi SM (2015) Dendrimers in medicine: therapeutic concepts and pharmaceutical challenges. Bioconjug Chem 26:1198–1211

    Article  PubMed  CAS  Google Scholar 

  • Xue X, Shi X, Dong H, You S, Cao H, Wang K, Wen Y, Shi D, He B, Li Y (2018) Delivery of MicroRNA-1 Inhibitor by dendrimer-based nanovector: an early targeting therapy for myocardial infarction in mice. Nanomedicine 14:619–631

    Article  PubMed  CAS  Google Scholar 

  • Yang H (2016) Targeted nanosystems: advances in targeted dendrimers for cancer therapy. Nanomedicine 12:309–316

    Article  PubMed  CAS  Google Scholar 

  • Yang R, Mao Y, Ye T, Xia S, Wang S, Wang S (2016) Study on enhanced lymphatic exposure of polyamidoamin-alkali blue dendrimer for paclitaxel delivery and influence of the osmotic pressure on the lymphatic targeting. Drug Deliv 23:2617–2629

    Article  PubMed  CAS  Google Scholar 

  • Yellepeddi VK, Kumar A, Maher DM, Chauhan SC, Vangara KK, Palakurthi S (2011) Biotinylated PAMAM dendrimers for intracellular delivery of cisplatin to ovarian cancer: role of SMVT. Anticancer Res 31:897–906

    PubMed  CAS  Google Scholar 

  • Zhang L, Zhu S, Qian L, Pei Y, Qiu Y, Jiang Y (2011a) RGD-modified PEG-PAMAM-DOX conjugates: in vitro and in vivo studies for glioma. Eur J Pharm Biopharm 79:232–240

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Thomas TP, Lee KH, Li M, Zong H, Desai AM, Kotlyar A, Huang B, Holl MM, Baker JR Jr (2011b) Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conjugate as a potential anticancer agent. Bioorg Med Chem 19:2557–2564

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang F, Nance E, Zhang Z, Jasty V, Kambhampati SP, Mishra MK, Burd I, Romero R, Kannan S, Kannan RM (2016a) Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers. J Control Release 237:61–70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang F, Nance E, Alnasser Y, Kannan R, Kannan S (2016b) Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation. J Neuroinflammation 13:65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zheng W, Cao C, Liu Y, Yu Q, Zheng C, Sun D, Ren X, Liu J (2015) Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance. Acta Biomater 11:368–380

    Article  PubMed  CAS  Google Scholar 

  • Zhong D, Tu Z, Zhang X, Li Y, Xu X, Gu Z (2017) Bioreducible peptide-dendrimeric nanogels with abundant expanded voids for efficient drug entrapment and delivery. Biomacromolecules 18:3498–3505

    Article  PubMed  CAS  Google Scholar 

  • Zhu S, Hong M, Tang G, Qian L, Lin J, Jiang Y, Pei Y (2010) Partly PEGylated polyamidoamine dendrimer for tumor-selective targeting of doxorubicin: the effects of PEGylation degree and drug conjugation style. Biomaterials 31:1360–1371

    Article  PubMed  CAS  Google Scholar 

  • Zong H, Thomas TP, Lee KH, Desai AM, Li MH, Kotlyar A, Zhang Y, Leroueil PR, Gam JJ, Banaszak Holl MM, Baker JR Jr (2012) Bifunctional PAMAM dendrimer conjugates of folic acid and methotrexate with defined ratio. Biomacromolecule 13:982–991

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Chung-Ang University Research Scholarship Grants in 2017. This work was supported by the National Research Foundation of Korea (NRF) Grants funded by the Ministry of Education (NRF-2016R1D1A1B03934847).

Author information

Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea

    Yejin Kim, Eun Ji Park & Dong Hee Na

Authors
  1. Yejin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eun Ji Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Hee Na
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong Hee Na.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, Y., Park, E.J. & Na, D.H. Recent progress in dendrimer-based nanomedicine development. Arch. Pharm. Res. 41, 571–582 (2018). https://doi.org/10.1007/s12272-018-1008-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-018-1008-4

Keywords

Search

Navigation