Structural nanomedicine
Structural nanomedicine is a field focused on the deliberate design of nanoscale therapeutics with precise compositions and architectures to optimize efficacy and safety. Structural nanomedicines emphasize molecularly defined designs where composition, spatial arrangement, and linker chemistry are systematically controlled. Small structural modifications can significantly influence therapeutic performance, including cellular uptake, circulation, immune activation, and target engagement.[1][2][3]
Background
Traditional pharmaceuticals were dominated by small molecules, where minor chemical changes (e.g., stereochemistry) could dramatically alter biological activity.[4] Biologics, including nucleic acids, peptides, and proteins, have since become the largest drug class, offering greater complexity and customization.[5] Early structural nanomedicines such as lipid nanoparticle (LNP) mRNA vaccines and liposomal constructs[6], are effective but structurally heterogeneous, with particle-to-particle variability influencing pharmacokinetics.
Principles and Design
Nanomedicines are being improved through deliberate, atomically precise design, enabling highly optimized therapeutics. Progress relies on interdisciplinary collaboration across chemistry, physics, materials science, biology, and medicine, with applications spanning cancer, infectious diseases, and autoimmune diseases. In the current wave of development, structural nanomedicines are advancing toward molecularly precise architectures that can be systematically altered and studied in an effort to make drugs with greater potency and more attractive safety profiles.[7][8]
Key classes of structural nanomedicines
Structural nanomedicines highlight structure as a critical design parameter alongside composition.
Lipid Nanoparticles (LNPs)
Lipid particle delivery systems, including the COVID-19 mRNA vaccines. These structures package the genetic mRNA component inside a lipid particle structure. In the case of the lipid particle mRNA vaccines for COVID-19, the mRNA snippets encode for the COVID-19 virus’s spike protein. Upon production and recognition, immunity against this protein is bolstered.[9]
Spherical Nucleic Acids (SNAs)
Spherical nucleic acids (SNAs), nanoparticle cores surrounded by radially oriented nucleic acids, were first described by Chad Mirkin (1996). SNAs show enhanced cellular uptake, nuclease resistance, and low toxicity compared with linear nucleic acids of the same sequence. SNAs are being used for gene regulation, CRISPR-based gene editing[10], and immunotherapy. Clinically, they are under investigation for the treatment of glioblastoma, acute myeloid leukemia (AML), psoriasis, squamous cell carcinoma, and Merkel cell carcinoma, with some forms leading to complete remission in checkpoint inhibitor–refractory cancers. [11][12]
MegaMolecules
MegaMolecules, introduced by Milan Mrksich, are multifunctional mimics of antibodies composed of fusion proteins joined with linkers.[13] They can incorporate binding domains, drugs, contrast agents, and radionuclides to achieve functionalities that make them useful in the detection and treatment of cancers.
Chemoflares and RNA-responsive constructs
Chemoflares are cell-responsive structural nanomedicines, designed to release therapeutic drugs only when they encounter disease-specific conditions inside the body, such as the unique environment of cancer cells. Developed by Chad Mirkin and Natalie Artzi, chemoflares stay inactive in healthy tissue but “flare” into action via cellular cues from diseased cells. This targeted activation improves treatment precision and reduces side effects. [14]
Protein-like Polymers (PLPs)
Protein-like Polymers (PLPs), invented by Nathan Gianneschi, are synthetic macromolecules designed to mimic the structure and function of natural proteins. They are built from polymer backbones densely grafted with peptide side chains, forming brush-like architectures that can fold, bind targets, and perform biological functions similar to proteins. These PLPs have been engineered to interact with specific receptors or disrupt disease-related protein interactions, showing promise for treating conditions such as macular degeneration and neurodegenerative diseases.[15]
References
- ↑ Mirkin, Chad A.; Langer, Robert; Mrksich, Milan; Margolin, Adam A.; Petrosko, Sarah Hurst; Artzi, Natalie (2025-05-27). "Blueprints for Better Drugs: The Structural Revolution in Nanomedicine". ACS Nano. 19 (20): 18889–18901. Bibcode:2025ACSNa..1918889M. doi:10.1021/acsnano.5c06380. ISSN 1936-0851. PMC 12168243 Check
|pmc=value (help). PMID 40359339 Check|pmid=value (help). Unknown parameter|pmc-embargo-date=ignored (help) - ↑ Wang, Shuya; Qin, Lei; Yamankurt, Gokay; Skakuj, Kacper; Huang, Ziyin; Chen, Peng-Cheng; Dominguez, Donye; Lee, Andrew; Zhang, Bin; Mirkin, Chad A. (2019-05-21). "Rational vaccinology with spherical nucleic acids". Proceedings of the National Academy of Sciences. 116 (21): 10473–10481. Bibcode:2019PNAS..11610473W. doi:10.1073/pnas.1902805116. PMC 6535021 Check
|pmc=value (help). PMID 31068463. - ↑ Hu, Qinqin; Li, Hua; Wang, Lihua; Gu, Hongzhou; Fan, Chunhai (2019-05-22). "DNA Nanotechnology-Enabled Drug Delivery Systems". Chemical Reviews. 119 (10): 6459–6506. Bibcode:2019ChRv..119.6459H. doi:10.1021/acs.chemrev.7b00663. ISSN 1520-6890. PMID 29465222.
- ↑ Evans, A. M. (November 2001). "Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen". Clinical Rheumatology. 20: S9–S14. doi:10.1007/BF03342662. ISSN 0770-3198. PMID 11771573.
- ↑ Beck, Alain; Wurch, Thierry; Bailly, Christian; Corvaia, Nathalie (May 2010). "Strategies and challenges for the next generation of therapeutic antibodies". Nature Reviews Immunology. 10 (5): 345–352. doi:10.1038/nri2747. ISSN 1474-1741. PMID 20414207.
- ↑ Hou, Xucheng; Zaks, Tal; Langer, Robert; Dong, Yizhou (December 2021). "Lipid nanoparticles for mRNA delivery". Nature Reviews Materials. 6 (12): 1078–1094. Bibcode:2021NatRM...6.1078H. doi:10.1038/s41578-021-00358-0. ISSN 2058-8437. PMC 8353930 Check
|pmc=value (help). PMID 34394960 Check|pmid=value (help). - ↑ Akinc, Akin; Zumbuehl, Andreas; Goldberg, Michael; Leshchiner, Elizaveta S.; Busini, Valentina; Hossain, Naushad; Bacallado, Sergio A.; Nguyen, David N.; Fuller, Jason; Alvarez, Rene; Borodovsky, Anna; Borland, Todd; Constien, Rainer; de Fougerolles, Antonin; Dorkin, J. Robert (May 2008). "A combinatorial library of lipid-like materials for delivery of RNAi therapeutics". Nature Biotechnology. 26 (5): 561–569. doi:10.1038/nbt1402. ISSN 1546-1696. PMC 3014085. PMID 18438401.
- ↑ Teplensky, Michelle H.; Evangelopoulos, Michael; Dittmar, Jasper W.; Forsyth, Connor M.; Sinegra, Andrew J.; Wang, Shuya; Mirkin, Chad A. (July 2023). "Multi-antigen spherical nucleic acid cancer vaccines". Nature Biomedical Engineering. 7 (7): 911–927. doi:10.1038/s41551-022-01000-2. ISSN 2157-846X. PMC 10424220 Check
|pmc=value (help). PMID 36717738 Check|pmid=value (help). - ↑ Patel, Rikin; Kaki, Mohamad; Potluri, Venkat S.; Kahar, Payal; Khanna, Deepesh (2022-12-31). "A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson". Human Vaccines & Immunotherapeutics. 18 (1): 2002083. doi:10.1080/21645515.2021.2002083. ISSN 2164-554X. PMC 8862159 Check
|pmc=value (help). PMID 35130825 Check|pmid=value (help). - ↑ Huang, Chi; Han, Zhenyu; Evangelopoulos, Michael; Mirkin, Chad A. (2022-10-19). "CRISPR Spherical Nucleic Acids". Journal of the American Chemical Society. 144 (41): 18756–18760. Bibcode:2022JAChS.14418756H. doi:10.1021/jacs.2c07913. ISSN 0002-7863. PMC 10430604 Check
|pmc=value (help). PMID 36201634 Check|pmid=value (help). - ↑ Kumthekar, Priya; Ko, Caroline H.; Paunesku, Tatjana; Dixit, Karan; Sonabend, Adam M.; Bloch, Orin; Tate, Matthew; Schwartz, Margaret; Zuckerman, Laura; Lezon, Ray; Lukas, Rimas V.; Jovanovic, Borko; McCortney, Kathleen; Colman, Howard; Chen, Si (2021-03-10). "A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma". Science Translational Medicine. 13 (584): eabb3945. doi:10.1126/scitranslmed.abb3945. PMC 8272521 Check
|pmc=value (help). PMID 33692132 Check|pmid=value (help). - ↑ O’Day, Steven; Perez, Cesar; Wise-Draper, Trisha; Hanna, Glenn; Bhatia, Shailender; Kelly, Ciara; Medina, Theresa; Laux, Douglas; Daud, Adil; Chandra, Sunandana; Shaheen, Montaser; Gao, Ling; Burgess, Melissa; Hernandez-Aya, Leonel; Yeung, Cecilia (December 2020). "423 Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors". Journal for Immunotherapy of Cancer. 8 (Suppl 3): A257.2–A258. doi:10.1136/jitc-2020-SITC2020.0423. ISSN 2051-1426.
- ↑ Modica, Justin A.; Iderzorig, Tsatsral; Mrksich, Milan (2020-08-12). "Design and Synthesis of Megamolecule Mimics of a Therapeutic Antibody". Journal of the American Chemical Society. 142 (32): 13657–13661. Bibcode:2020JAChS.14213657M. doi:10.1021/jacs.0c05093. ISSN 0002-7863. PMC 8534297 Check
|pmc=value (help). PMID 32706963 Check|pmid=value (help). - ↑ Halo, Tiffany L.; McMahon, Kaylin M.; Angeloni, Nicholas L.; Xu, Yilin; Wang, Wei; Chinen, Alyssa B.; Malin, Dmitry; Strekalova, Elena; Cryns, Vincent L.; Cheng, Chonghui; Mirkin, Chad A.; Thaxton, C. Shad (2014-12-02). "NanoFlares for the detection, isolation, and culture of live tumor cells from human blood". Proceedings of the National Academy of Sciences. 111 (48): 17104–17109. Bibcode:2014PNAS..11117104H. doi:10.1073/pnas.1418637111. PMC 4260589. PMID 25404304.
- ↑ Choi, Wonmin; Nensel, Ashley K.; Droho, Steven; Fattah, Mara A.; Mokashi-Punekar, Soumitra; Swygart, David I.; Burton, Spencer T.; Schwartz, Greg W.; Lavine, Jeremy A.; Gianneschi, Nathan C. (2023-10-13). "Thrombospondin-1 proteomimetic polymers exhibit anti-angiogenic activity in a neovascular age-related macular degeneration mouse model". Science Advances. 9 (41): eadi8534. Bibcode:2023SciA....9I8534C. doi:10.1126/sciadv.adi8534. PMC 10575579 Check
|pmc=value (help). PMID 37831763 Check|pmid=value (help).
This article "Structural nanomedicine" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Structural nanomedicine. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
