Design and biomedical applications of core-shell tecto dendrimers

doi:10.16352/j.issn.1001-6325.2022.01.010

Abstract

Abstract: Core-shell tecto dendrimers (CSTDs) are a kind of superstructured dendrimeric nanoconstructs with relatively high-generation dendrimers as the cores and low-generation dendrimers as the shells. Recently, there is growing evidence that the performance of CSTDs constructed with poly(amidoamine) (PAMAM) dendrimers of different generations as reactive modules is not only superior to that of single-generation dendrimers, but also overcomes some biomedical limitations (e.g., restricted drug loading capacity, limited tumor passive targeting based on enhanced permeability and retention effect) of single-generation dendrimers. Herein, the design of CSTDs for biological imaging, chemotherapy, gene therapy, and combination therapy are reviewed. The current challenges and future development prospects of CSTDs in the field of biomedicine are also analyzed.

Key words: core-shell tecto dendrimers, poly(amidoamine) dendrimers, synthesis, imaging, therapy

CLC Number:

Q819

SONG Cong, WANG Da-yuan, SHEN Ming-wu, SHI Xiang-yang. Design and biomedical applications of core-shell tecto dendrimers[J]. Basic & Clinical Medicine, 2022, 42(1): 15-25.

References

[1]Xiao T, Li D, Shi X, et al. PAMAM dendrimer-based nanodevices for nuclear medicine applications[J]. Macromol Biosci, 2020, 20: 1900282
[2]Hawker CJ, Frechet JMJ. Preparation of polymers with controlled molecular architecture-a new convergent approach to dendritic macromolecules[J]. J Am Chem Soc, 1990, 112: 7638-7647.
[3]Mignani S, Rodrigues J, Tomas H, et al. Dendrimers in combination with natural products and analogues as anti-cancer agents[J]. Chem Soc Rev, 2018, 47: 514-532.
[4]Liu J, Xiong Z, Zhang J, et al. Zwitterionic gadolinium(Ⅲ)-complexed dendrimer-entrapped gold nanoparticles for enhanced computed tomography/magnetic resonance imaging of lung cancer metastasis[J]. ACS Appl Mater Interfaces, 2019, 11: 15212-15221.
[5]Zhao L, Wen S, Zhu M, et al. ^99mTc labeled multifunctional polyethylenimine-entrapped gold nanoparticles for dual mode SPECT and CT imaging[J]. Artif Cells Nanomed Biotechnol, 2018,46:488-498.
[6]Zhu J, Zheng L, Wen S, et al. Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles[J]. Biomaterials, 2014, 35: 7635-7646.
[7]Wang Y, Guo R, Cao X, et al. Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine) dendrimers for targeted cancer therapy[J]. Biomaterials, 2011, 32: 3322-3329.
[8]Kong L, Alves CS, Hou W, et al. RGD peptide-modified dendrimer-entrapped gold nanoparticles enable highly efficient and specific gene delivery to stem cells[J]. ACS Appl Mater Interfaces, 2015, 7: 4833-4843.
[9]Shan Y, Luo T, Peng C, et al. Gene delivery using dendrimer-entrapped gold nanoparticles as nonviral vectors[J]. Biomaterials, 2012, 33: 3025-3035.
[10]Zhu J, Shi X. Dendrimer-based nanodevices for targeted drug delivery applications[J]. J Mater Chem B, 2013, 1: 4199-4211.
[11]Kong L, Xing L, Zhou B, et al. Dendrimer-modified MoS2 nanoflakes as a platform for combinational gene silencing and photothermal therapy of tumors[J]. ACS Appl Mater Interfaces, 2017, 9: 15995-16005.
[12]Kala S, Mak ASC, Liu X, et al. Combination of dendrimer-nanovector-mediated small interfering RNA delivery to target Akt with the clinical anticancer drug paclitaxel for effective and potent anticancer activity in treating ovarian cancer[J]. J Med Chem, 2014, 57: 2634-2642.
[13]Zhao L, Zhu J, Cheng Y, et al. Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide I-131 for single photon emission computed tomography imaging and radiotherapy of gliomas[J]. ACS Appl Mater Interfaces, 2015, 7: 19798-19808.
[14]Menjoge AR, Kannan RM, Tomalia DA. Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications[J]. Drug Discov Today, 2010, 15: 171-185.
[15]Zhu J, Wang G, Alves CS, et al. Multifunctional dendrimer-entrapped gold nanoparticles conjugated with doxorubicin for pH-responsive drug delivery and targeted computed tomography imaging[J]. Langmuir, 2018, 34: 12428-12435.
[16]Liu H, Wang H, Yang W, et al. Disulfide cross-linked low generation dendrimers with high gene transfection efficacy, low cytotoxicity, and low cost[J]. J Am Chem Soc, 2012, 134: 17680-17687.
[17]Haensler J, Szoka FC. Polyamidomine cascade polymers mediate efficient transfection of cells in culture[J]. Bioconjugate Chem, 1993, 4: 372-379.
[18]Kukowska-Latallo JF, Bielinska AU, Johnson J, et al. Efficient transfer of genetic material into mammalian cells using starburst polyamidoamine dendrimers[J]. Proc Natl Acad Sci U S A, 1996, 93: 4897-4902.
[19]Cheng Y, Li Y, Wu Q, et al. Generation-dependent encapsulation/electrostatic attachment of phenobarbital molecules by poly(amidoamine) dendrimers: Evidence from 2D-NOESY investigations[J]. Eur J Med Chem, 2009, 44: 2219-2223.
[20]Hong S, Leroueil PR, Janus EK, et al. Interaction of polycationic polymers with supported lipid bilayers and cells: Nanoscale hole formation and enhanced membrane permeability[J]. Bioconjugate Chem, 2006, 17: 728-734.
[21]Hong S, Rattan R, Majoros IJ, et al. The role of ganglioside GM(1) in cellular internalization mechanisms of poly(amidoamine) dendrimers[J]. Bioconjugate Chem, 2009, 20: 1503-1513.
[22]Malik N, Wiwattanapatapee R, Klopsch R, et al. Dendrimers: Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribu-tion of I-125-labelled polyamidoamine dendrimers in vivo[J]. J Controlled Release, 2000, 68: 299-302.
[23]Song C, Shen M, Rodrigues J, et al. Superstructured poly(amidoamine) dendrimer-based nanoconstructs as plat-forms for cancer nanomedicine: A concise review[J]. Coord Chem Rev, 2020, 421: 213463.
[24]Uppuluri S, Swanson DR, Piehler LT, et al. Core-shell tecto(dendrimers): I. Synthesis and characterization of saturated shell models[J]. Adv Mater, 2000, 12: 796-800.
[25]Chen F, Kong L, Wang L, et al. Construction of core-shell tecto dendrimers based on supramolecular host-guest assembly for enhanced gene delivery[J]. J Mater Chem B, 2017, 5: 8459-8466.
[26]Song C, Gao Y, Chen J, et al. Physicochemical aspects of zwitterionic core-shell tecto dendrimers characterized by a thorough NMR investigation[J]. Colloids Surf A, 2021, 618: 126466.
[27]Choi YS, Mecke A, Orr BG, et al. DNA-directed synthesis of generation 7 and 5 PAMAM dendrimer nanoclusters[J]. Nano Lett, 2004, 4: 391-397.
[28]Choi Y, Baker JR. Targeting cancer cells with DNA-assembled dendrimers-A mix and match strategy for cancer[J]. Cell Cycle, 2005, 4: 669-671.
[29]Choi Y, Thomas T, Kotlyar A, et al. Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting[J]. Chem Biol, 2005, 12: 35-43.
[30]Cheng Z, Thorek DLJ, Tsourkas A. Gadolinium-conjug-ated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent[J]. Angew Chem Int Ed, 2010, 49: 346-350.
[31]Huang CH, Nwe K, Al Zaki A, et al. Biodegradable polydisulfide dendrimer nanoclusters as MRI contrast agents[J]. ACS Nano, 2012, 6: 9416-9424.
[32]Zhang D, Hamilton PD, Kao JLF, et al. Formation of nanogel aggregates by an amphiphilic cholesteryl-poly(amidoamine) dendrimer in aqueous media[J]. J Polym Sci Part A Polym Chem, 2007, 45: 2569-2575.
[33]Goncalves M, Maciel D, Capelo D, et al. Dendrimer-assisted formation of fluorescent nanogels for drug delivery and intracellular imaging[J]. Biomacromolecules, 2014, 15: 492-499.
[34]Li HJ, Du JZ, Du XJ, et al. Stimuli-responsive clustered nanoparticles for improved tumor penetration and thera-peutic efficacy[J]. Proc Natl Acad Sci U S A, 2016, 113: 4164-4169.
[35]Li HJ, Du JZ, Liu J, et al. Smart superstructures with ultrahigh pH-sensitivity for targeting acidic tumor microenvironment: instantaneous size switching and improved tumor penetration[J]. ACS Nano, 2016, 10: 6753-6761.
[36]Tomalia DA, Brothers HM, Piehler LT, et al. Partial shell-filled core-shell tecto(dendrimers): A strategy to surface differentiated nano-clefts and cusps[J]. Proc Natl Acad Sci U S A, 2002, 99: 5081-5087.
[37]Tomalia DA. Birth of a new macromolecular architecture: dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry[J]. Prog Polym Sci, 2005, 30: 294-324.
[38]Li J, Swanson DR, Qin D, et al. Characterizations of core-shell tecto-(dendrimer) molecules by tapping mode atomic force microscopy[J]. Langmuir, 1999, 15: 7347-7350.
[39]Schilrreff P, Mundina-Weilenmann C, Lilia Romero E, et al. Selective cytotoxicity of PAMAM G5 core-PAMAM G2.5 shell tecto-dendrimers on melanoma cells[J]. Int J Nanomed, 2012, 7: 4121-4133.
[40]Studzian M, Działak P, Pułaski Ł, et al. Synthesis, internalization and visualization of N-(4-carbomethoxy) pyrrolidone terminated PAMAM [G5:G3-TREN]tecto(dendrimers) in mammalian cells[J]. Molecules, 2020, 25: 4406.
[41]Schmidt BVKJ, Barner-Kowollik C. Dynamic macromolecular material design-The versatility of cyclodextrin-based host-guest chemistry[J]. Angew Chem Int Ed, 2017, 56: 8350-8369.
[42]Rekharsky MV, Inoue Y. Complexation thermodynamics of cyclodextrins[J]. Chem Rev, 1998, 98: 1875-1918.
[43]Ma X, Zhao Y. Biomedical applications of supramolecular systems based on host-guest interactions[J]. Chem Rev, 2015, 115: 7794-7839.
[44]Song C, Ouyang Z, Guo H, et al. Core-shell tecto dendrimers enable enhanced tumor mr imaging through an amplified EPR effect[J]. Biomacromolecules, 2021, 22: 2181-2188.
[45]Wang J, Li D, Fan Y, et al. Core-shell tecto dendrimers formed via host-guest supramolecular assembly as pH-responsive intelligent carriers for enhanced anticancer drug delivery[J]. Nanoscale, 2019, 11: 22343-22350.
[46]Volz P, Schilrreff P, Brodwolf R, et al. Pitfalls in using fluorescence tagging of nanomaterials: tecto-dendrimers in skin tissue as investigated by Cluster-FLIM[J]. Ann N Y Acad Sci, 2017, 1405: 202-214.
[47]Murta V, Schilrreff P, Rosciszewski G, et al. G5G2.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia[J]. J Neurochem, 2018, 144: 748-760.
[48]Schilrreff P, Cervini G, Romero E, et al. Enhanced antimelanoma activity of methotrexate and zoledronic acid within polymeric sandwiches[J]. Colloids Surf B, 2014, 122: 19-29.
[49]Wang D, Chen L, Gao Y, et al. Impact of molecular rigidity on the gene delivery efficiency of core-shell tecto dendrimers[J]. J Mater Chem B, 2021, 9: 6149-6154.
[50]Song C, Xiao Y, Ouyang Z, et al. Efficient co-delivery of microRNA 21 inhibitor and doxorubicin to cancer cells using core-shell tecto dendrimers formed via supramolecular host-guest assembly[J]. J Mater Chem B, 2020, 8: 2768-2774.
[51]Qiao Z, Shi X. Dendrimer-based molecular imaging contrast agents[J]. Prog Polym Sci, 2015, 44: 1-27.
[52]Zhu J, Xiong Z, Shen M, et al. Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells[J]. RSC Adv, 2015, 5: 30286-30296.
[53]Xiong Z, Wang Y, Zhu J, et al. Gd-Chelated poly(propylene imine) dendrimers with densely organized maltose shells for enhanced MR imaging applications[J]. Biomater Sci, 2016, 4: 1622-1629.
[54]Liu R, Guo H, Ouyang Z, et al. Multifunctional core-shell tecto dendrimers incorporated with gold nanoparticles for targeted dual mode CT/MR imaging of tumors[J]. ACS Appl Bio Mater, 2021, 4: 1803-1812.