Multifunctional biomolecule nanostructures for cancer therapy
Source abstract
Abstract
Biomolecule-based nanostructures are inherently multifunctional and harbour diverse biological activities, which can be explored for cancer nanomedicine. The supramolecular properties of biomolecules can be precisely programmed for the design of smart drug delivery vehicles, enabling efficient transport in vivo, targeted drug delivery and combinatorial therapy within a single design. In this Review, we discuss biomolecule-based nanostructures, including polysaccharides, nucleic acids, peptides and proteins, and highlight their enormous design space for multifunctional nanomedicines. We identify key challenges in cancer nanomedicine that can be addressed by biomolecule-based nanostructures and survey the distinct biological activities, programmability and in vivo behaviour of biomolecule-based nanostructures. Finally, we discuss challenges in the rational design, characterization and fabrication of biomolecule-based nanostructures, and identify obstacles that need to be overcome to enable clinical translation.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · Nanoplatforms for cancer theranostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20 (2016).10.1038/nrc.2016.108 ↗
2. Chen, H., Zhang, W., Zhu, G., Xie, J. & Chen, X. Rethinking cancer nanotheranostics. Nat. Rev. Mater. 2, 17024 (2017).10.1038/natrevmats.2017.24 ↗
3. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).10.1126/science.1214081 ↗
4. Anselmo, A. C. & Mitragotri, S. Nanoparticles in the clinic: an update. Bioeng. Transl. Med. 4, e10143 (2019).10.1002/btm2.10143 ↗
5. Zhao, Z., Ukidve, A., Kim, J. & Mitragotri, S. Targeting strategies for tissue-specific drug delivery. Cell 181, 151–167 (2020).10.1016/j.cell.2020.02.001 ↗
6. Cheng, Z., Al Zaki, A., Hui, J. Z., Muzykantov, V. R. & Tsourkas, A. Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science 338, 903 (2012).10.1126/science.1226338 ↗
7. Datta, L. P., Manchineella, S. & Govindaraju, T. Biomolecules-derived biomaterials. Biomaterials 230, 119633 (2020).10.1016/j.biomaterials.2019.119633 ↗
8. Liu, K., Jiang, X. & Hunziker, P. Carbohydrate-based amphiphilic nano delivery systems for cancer therapy. Nanoscale 8, 16091–16156 (2016).10.1039/C6NR04489A ↗
9. Habibi, N., Kamaly, N., Memic, A. & Shafiee, H. Self-assembled peptide-based nanostructures: smart nanomaterials toward targeted drug delivery. Nano Today 11, 41–60 (2016).10.1016/j.nantod.2016.02.004 ↗
10. Kakkar, A., Traverso, G., Farokhzad, O. C., Weissleder, R. & Langer, R. Evolution of macromolecular complexity in drug delivery systems. Nat. Rev. Chem. 1, 63 (2017).10.1038/s41570-017-0063 ↗
11. Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2018).10.1038/natrevmats.2017.68 ↗
12. Lammers, T. et al. Cancer nanomedicine: is targeting our target? Nat. Rev. Mater. 1, 16069 (2016).10.1038/natrevmats.2016.69 ↗
13. Bobo, D., Robinson, K. J., Islam, J., Thurecht, K. J. & Corrie, S. R. Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm. Res. 33, 2373–2387 (2016).10.1007/s11095-016-1958-5 ↗
14. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).10.1016/j.cell.2011.02.013 ↗
15. Valkenburg, K. C., de Groot, A. E. & Pienta, K. J. Targeting the tumour stroma to improve cancer therapy. Nat. Rev. Clin. Oncol. 15, 366–381 (2018).10.1038/s41571-018-0007-1 ↗
16. Ji, T. et al. Transformable peptide nanocarriers for expeditious drug release and effective cancer therapy via cancer-associated fibroblast activation. Angew. Chem. Int. Ed. 55, 1050–1055 (2016).10.1002/anie.201506262 ↗
17. Han, X. et al. Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem. Nat. Commun. 9, 3390 (2018).10.1038/s41467-018-05906-x ↗
18. Li, S. et al. Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles. Nat. Biomed. Eng. 4, 732–742 (2020).10.1038/s41551-020-0573-2 ↗
19. Metselaar, J. M. & Lammers, T. Challenges in nanomedicine clinical translation. Drug Deliv. Transl. Res. 10, 721–725 (2020).10.1007/s13346-020-00740-5 ↗
20. Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater. 8, 543–557 (2009).10.1038/nmat2442 ↗
21. Cai, R. & Chen, C. The crown and the scepter: roles of the protein corona in nanomedicine. Adv. Mater. 31, 1805740 (2019).10.1002/adma.201805740 ↗
22. Banerjee, I., Pangule, R. C. & Kane, R. S. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv. Mater. 23, 690–718 (2011).10.1002/adma.201001215 ↗
23. Chelmowski, R. et al. Peptide-based SAMs that resist the adsorption of proteins. J. Am. Chem. Soc. 130, 14952–14953 (2008).10.1021/ja8065754 ↗
24. Tonigold, M. et al. Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona. Nat. Nanotechnol. 13, 862–869 (2018).10.1038/s41565-018-0171-6 ↗
25. Hamad-Schifferli, K. Exploiting the novel properties of protein coronas: emerging applications in nanomedicine. Nanomedicine 10, 1663–1674 (2015).10.2217/nnm.15.6 ↗
26. Setten, R. L., Rossi, J. J. & Han, S.-P. The current state and future directions of RNAi-based therapeutics. Nat. Rev. Drug Discov. 18, 421–446 (2019).10.1038/s41573-019-0017-4 ↗
27. Zhang, Z. et al. Brain-targeted drug delivery by manipulating protein corona functions. Nat. Commun. 10, 3561 (2019).10.1038/s41467-019-11593-z ↗
28. Mirshafiee, V., Kim, R., Park, S., Mahmoudi, M. & Kraft, M. L. Impact of protein pre-coating on the protein corona composition and nanoparticle cellular uptake. Biomaterials 75, 295–304 (2016).10.1016/j.biomaterials.2015.10.019 ↗
29. Owens, D. E. & Peppas, N. A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307, 93–102 (2006).10.1016/j.ijpharm.2005.10.010 ↗
30. Zhang, P., Sun, F., Liu, S. & Jiang, S. Anti-PEG antibodies in the clinic: current issues and beyond PEGylation. J. Control. Rel. 244, 184–193 (2016).10.1016/j.jconrel.2016.06.040 ↗
31. Hu, C.-M. J. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980 (2011).10.1073/pnas.1106634108 ↗
32. Rodriguez, P. L. et al. Minimal ‘self’ peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science 339, 971 (2013).10.1126/science.1229568 ↗
33. Kim, J. et al. Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance. Biomaterials 147, 14–25 (2017).10.1016/j.biomaterials.2017.08.045 ↗
34. Kang, T. et al. Nanoparticles coated with neutrophil membranes can effectively treat cancer metastasis. ACS Nano 11, 1397–1411 (2017).10.1021/acsnano.6b06477 ↗
35. Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).10.1038/s41565-020-0669-6 ↗
36. Blanco, E., Shen, H. & Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941 (2015).10.1038/nbt.3330 ↗
37. Nichols, J. W. & Bae, Y. H. EPR: evidence and fallacy. J. Control. Rel. 190, 451–464 (2014).10.1016/j.jconrel.2014.03.057 ↗
38. Nakamura, H., Jun, F. & Maeda, H. Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls. Expert Opin. Drug Deliv. 12, 53–64 (2015).10.1517/17425247.2014.955011 ↗
39. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1, 16014 (2016).10.1038/natrevmats.2016.14 ↗
40. Li, S. et al. Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours. Nat. Biomed. Eng. 1, 667–679 (2017).10.1038/s41551-017-0115-8 ↗
41. Miller, M. A. et al. Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle. Sci. Transl. Med. 7, 314ra183 (2015).10.1126/scitranslmed.aac6522 ↗
42. Shah, S., Liu, Y., Hu, W. & Gao, J. Modeling particle shape-dependent dynamics in nanomedicine. J. Nanosci. Nanotechnol. 11, 919–928 (2011).10.1166/jnn.2011.3536 ↗
43. Liang, Q. et al. The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency. Nat. Biomed. Eng. 3, 729–740 (2019).10.1038/s41551-019-0405-4 ↗
44. Palomba, R. et al. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability. Sci. Rep. 6, 34422 (2016).10.1038/srep34422 ↗
45. Sindhwani, S. et al. The entry of nanoparticles into solid tumours. Nat. Mater. 19, 566–575 (2020).10.1038/s41563-019-0566-2 ↗
46. Liu, X., Jiang, J. & Meng, H. Transcytosis — an effective targeting strategy that is complementary to ‘EPR effect’ for pancreatic cancer nano drug delivery. Theranostics 9, 8018–8025 (2019).10.7150/thno.38587 ↗
47. Pandit, S., Dutta, D. & Nie, S. Active transcytosis and new opportunities for cancer nanomedicine. Nat. Mater. 19, 478–480 (2020).10.1038/s41563-020-0672-1 ↗
48. Guo, Y. et al. Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma. ACS Nano 9, 6918–6933 (2015).10.1021/acsnano.5b01042 ↗
49. Xu, J. et al. Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment. Biomaterials 216, 119247 (2019).10.1016/j.biomaterials.2019.119247 ↗
50. Shields, C. W. et al. Cellular backpacks for macrophage immunotherapy. Sci. Adv. 6, eaaz6579 (2020).10.1126/sciadv.aaz6579 ↗
51. Ngambenjawong, C., Gustafson, H. H. & Pun, S. H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev. 114, 206–221 (2017).10.1016/j.addr.2017.04.010 ↗
52. Dowdy, S. F. Overcoming cellular barriers for RNA therapeutics. Nat. Biotechnol. 35, 222–229 (2017).10.1038/nbt.3802 ↗
53. Thambi, T., Phan, V. H. G. & Lee, D. S. Stimuli-sensitive injectable hydrogels based on polysaccharides and their biomedical applications. Macromol. Rapid Commun. 37, 1881–1896 (2016).10.1002/marc.201600371 ↗
54. Lin, N., Huang, J. & Dufresne, A. Preparation, properties and applications of polysaccharide nanocrystals in advanced functional nanomaterials: a review. Nanoscale 4, 3274–3294 (2012).10.1039/c2nr30260h ↗
55. Hu, H. et al. Redox-responsive polycation-functionalized cotton cellulose nanocrystals for effective cancer treatment. ACS Appl. Mater. Interfaces 7, 8942–8951 (2015).10.1021/acsami.5b02432 ↗
56. Swierczewska, M., Han, H. S., Kim, K., Park, J. H. & Lee, S. Polysaccharide-based nanoparticles for theranostic nanomedicine. Adv. Drug Deliv. Rev. 99, 70–84 (2016).10.1016/j.addr.2015.11.015 ↗
57. Butt, A. M. et al. Doxorubicin and siRNA codelivery via chitosan-coated pH-responsive mixed micellar polyplexes for enhanced cancer therapy in multidrug-resistant tumors. Mol. Pharm. 13, 4179–4190 (2016).10.1021/acs.molpharmaceut.6b00776 ↗
58. Shi, G.-N. et al. Enhanced antitumor immunity by targeting dendritic cells with tumor cell lysate-loaded chitosan nanoparticles vaccine. Biomaterials 113, 191–202 (2017).10.1016/j.biomaterials.2016.10.047 ↗
59. Thambi, T. et al. Bioreducible carboxymethyl dextran nanoparticles for tumor-targeted drug delivery. Adv. Healthc. Mater. 3, 1829–1838 (2014).10.1002/adhm.201300691 ↗
60. Han, H. S. et al. Bioreducible shell-cross-linked hyaluronic acid nanoparticles for tumor-targeted drug delivery. Biomacromolecules 16, 447–456 (2015).10.1021/bm5017755 ↗
61. Wang, X. et al. Amphiphilic carboxymethyl chitosan–quercetin conjugate with P-gp inhibitory properties for oral delivery of paclitaxel. Biomaterials 35, 7654–7665 (2014).10.1016/j.biomaterials.2014.05.053 ↗
62. Schmidt, K. T. et al. Measurement of NLG207 (formerly CRLX101) nanoparticle-bound and released camptothecin in human plasma. J. Pharm. Biomed. Anal. 181, 113073 (2020).10.1016/j.jpba.2019.113073 ↗
63. Choi, K. Y. et al. Versatile RNA interference nanoplatform for systemic delivery of RNAs. ACS Nano 8, 4559–4570 (2014).10.1021/nn500085k ↗
64. Lallana, E. et al. Chitosan/hyaluronic acid nanoparticles: rational design revisited for RNA delivery. Mol. Pharm. 14, 2422–2436 (2017).10.1021/acs.molpharmaceut.7b00320 ↗
65. Kim, T. et al. Nanoparticle-patterned multicompartmental chitosan capsules for oral delivery of oligonucleotides. ACS Biomater. Sci. Eng. 4, 4163–4173 (2018).10.1021/acsbiomaterials.8b00806 ↗
66. Wu, L. et al. A review about the development of fucoidan in antitumor activity: progress and challenges. Carbohydr. Polym. 154, 96–111 (2016).10.1016/j.carbpol.2016.08.005 ↗
67. Shamay, Y. et al. P-selectin is a nanotherapeutic delivery target in the tumor microenvironment. Sci. Transl. Med. 8, 345ra87 (2016).10.1126/scitranslmed.aaf7374 ↗
68. Juenet, M. et al. Thrombolytic therapy based on fucoidan-functionalized polymer nanoparticles targeting P-selectin. Biomaterials 156, 204–216 (2018).10.1016/j.biomaterials.2017.11.047 ↗
69. Otterlei, M. et al. Induction of cytokine production from human monocytes stimulated with alginate. J. Immunother. 10, 286–291 (1991).10.1097/00002371-199108000-00007 ↗
70. Jani, M. S., Veetil, A. T. & Krishnan, Y. Precision immunomodulation with synthetic nucleic acid technologies. Nat. Rev. Mater. 4, 451–458 (2019).10.1038/s41578-019-0105-4 ↗
71. Zhao, Y. et al. Nanofabrication based on DNA nanotechnology. Nano Today 26, 123–148 (2019).10.1016/j.nantod.2019.03.004 ↗
72. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).10.1016/0022-5193(82)90002-9 ↗
73. Guo, P., Zhang, C., Chen, C., Garver, K. & Trottier, M. Inter-RNA interaction of phage phi29 pRNA to form a hexameric complex for viral DNA transportation. Mol. Cell 2, 149–155 (1998).10.1016/S1097-2765(00)80124-0 ↗
74. Guo, P. The emerging field of RNA nanotechnology. Nat. Nanotechnol. 5, 833–842 (2010).10.1038/nnano.2010.231 ↗
75. Xu, C. et al. Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy. Cancer Lett. 414, 57–70 (2018).10.1016/j.canlet.2017.09.043 ↗
76. Jasinski, D., Haque, F., Binzel, D. W. & Guo, P. Advancement of the emerging field of RNA nanotechnology. ACS Nano 11, 1142–1164 (2017).10.1021/acsnano.6b05737 ↗
77. Watts, J. K., Deleavey, G. F. & Damha, M. J. Chemically modified siRNA: tools and applications. Drug Discov. Today 13, 842–855 (2008).10.1016/j.drudis.2008.05.007 ↗
78. Piao, X., Xia, X., Mao, J. & Bong, D. Peptide ligation and RNA cleavage via an abiotic template interface. J. Am. Chem. Soc. 137, 3751–3754 (2015).10.1021/jacs.5b00236 ↗
79. Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).10.1038/28998 ↗
80. Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).10.1038/nature04586 ↗
81. Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012).10.1038/nature11075 ↗
82. Ali, M. M. et al. Rolling circle amplification: a versatile tool for chemical biology, materials science and medicine. Chem. Soc. Rev. 43, 3324–3341 (2014).10.1039/c3cs60439j ↗
83. Wang, C., Sun, W., Wright, G., Wang, A. Z. & Gu, Z. Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and anti-PD1 antibody. Adv. Mater. 28, 8912–8920 (2016).10.1002/adma.201506312 ↗
84. Ramezani, H. & Dietz, H. Building machines with DNA molecules. Nat. Rev. Genet. 21, 5–26 (2020).10.1038/s41576-019-0175-6 ↗
85. Wang, P., Ko, S. H., Tian, C., Hao, C. & Mao, C. RNA–DNA hybrid origami: folding of a long RNA single strand into complex nanostructures using short DNA helper strands. Chem. Commun. 49, 5462–5464 (2013).10.1039/c3cc41707g ↗
86. Zhou, J. & Rossi, J. Aptamers as targeted therapeutics: current potential and challenges. Nat. Rev. Drug Discov. 16, 181–202 (2017).10.1038/nrd.2016.199 ↗
87. Li, L. et al. Nucleic acid aptamers for molecular diagnostics and therapeutics: advances and perspectives. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.202003563 (2020).10.1002/anie.202003563 ↗
88. Ren, K. et al. A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery. Nat. Commun. 7, 13580 (2016).10.1038/ncomms13580 ↗
89. Ma, W. et al. An intelligent DNA nanorobot with in vitro enhanced protein lysosomal degradation of HER2. Nano Lett. 19, 4505–4517 (2019).10.1021/acs.nanolett.9b01320 ↗
90. Jiang, D. et al. Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl. Mater. Interfaces 8, 4378–4384 (2016).10.1021/acsami.5b10792 ↗
91. Lee, H. et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 7, 389–393 (2012).10.1038/nnano.2012.73 ↗
92. Zhang, Q. et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano 8, 6633–6643 (2014).10.1021/nn502058j ↗
93. Yang, Y. et al. G-quadruplex-based nanoscale coordination polymers to modulate tumor hypoxia and achieve nuclear-targeted drug delivery for enhanced photodynamic therapy. Nano Lett. 18, 6867–6875 (2018).10.1021/acs.nanolett.8b02732 ↗
94. Veetil, A. T. et al. Cell-targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules. Nat. Nanotechnol. 12, 1183–1189 (2017).10.1038/nnano.2017.159 ↗
95. Bujold, K. E., Hsu, J. C. C. & Sleiman, H. F. Optimized DNA ‘nanosuitcases’ for encapsulation and conditional release of siRNA. J. Am. Chem. Soc. 138, 14030–14038 (2016).10.1021/jacs.6b08369 ↗
96. Ranallo, S., Prevost-Tremblay, C., Idili, A., Vallee-Belisle, A. & Ricci, F. Antibody-powered nucleic acid release using a DNA-based nanomachine. Nat. Commun. 8, 15150 (2017).10.1038/ncomms15150 ↗
97. Amir, Y. et al. Universal computing by DNA origami robots in a living animal. Nat. Nanotechnol. 9, 353–357 (2014).10.1038/nnano.2014.58 ↗
98. Arnon, S. et al. Thought-controlled nanoscale robots in a living host. PLoS ONE 11, e0161227 (2016).10.1371/journal.pone.0161227 ↗
99. Li, S. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 36, 258–264 (2018).10.1038/nbt.4071 ↗
100. Ma, P. Q., Huang, Q., Li, H. D., Yin, B. C. & Ye, B. C. Multimachine communication network that mimics the adaptive immune response. J. Am. Chem. Soc. 142, 3851–3861 (2020).10.1021/jacs.9b11545 ↗