A removable bio-orthogonal catalytic patch: A local “landmine”

Recently, Zhejiang University scientists developed a local “landmine.” They engineered patch device consisting of microneedle arrays integrated with palladium nanoparticles supported by TiO2 nanosheets to catalyze prodrug-into-drug conversion via bio-orthogonal reaction for tumor inhibition. This study provides novel paradigm biological application chemistry in treatment. From patches therapy, our understanding smart drug delivery systems continues evolve the efforts bold innovators. Professor Zhen Gu, from University, is one most outstanding biomedical engineering world. He innovatively proposes blood sugar-responsive “smart insulin patch” concept closed-circuit transdermal system and further systematically expands its application. As recently described Nature Nanotechnology,1Chen Z. Li H. Bian Y. Wang Chen G. Zhang X. Miao Wen D. J. Wan et al.Bioorthogonal catalytic patch.Nat. Nanotechnol. 2021; https://doi.org/10.1038/s41565-021-00910-7Crossref Scopus (29) Google Scholar Gu group applied construct catalyst carrier achieve activation innocuous prodrug at site. like planting landmine tumor: when are combined, will detonate then kill precisely. Bio-orthogonal chemical reactions that neither interact nor interfere under biocompatible conditions. catalysis based on abiotic transition metals (TMs), including Pd, Ru, Cu, has achieved series exciting new applications control spatiotemporally prodrugs proteins direct manipulation intact cells physiological conditions.2Li P.R. Development bond cleavage bioorthogonal chemistry.Nat. Chem. Biol. 2016; 12: 129-137https://doi.org/10.1038/nchembio.2024Crossref PubMed (266) Scholar,3Sancho-Albero M. Rubio-Ruiz B. Pérez-López A.M. Sebastián V. Martín-Duque P. Arruebo Santamaría Unciti-Broceta A. Cancer-derived exosomes loaded ultrathin targeted catalysis.Nat. Catal. 2019; 2: 864-872https://doi.org/10.1038/s41929-019-0333-4Crossref (107) However, due safety issues TMs toxicity, off-target effect limited stability, effective living organism still challenging.4Latocheski E. Dal Forno G.M. Ferreira T.M. Oliveira B.L. Bernardes G.J.L. Domingos J.B. Mechanistic insights into metal-mediated uncaging reactions.Chem. Soc. Rev. 2020; 49: 7710-7729https://doi.org/10.1039/d0cs00630kCrossref (17) Moreover, there concerns about how withdraw after treatment avoid immunogenicity unexpected reaction. The development removable mediate decaging active state subcutaneous sites can reduce off-targeting side effects, as al. recent issue Nanotechnology.1Chen Let us shuttle through explore “landmine” constructed. shown Figure 1, this work group’s previous patches.5Chen Zeng Dotti Wirz R.E. Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy.Proc. Natl. Acad. Sci. USA. 117: 3687-3692https://doi.org/10.1073/pnas.1917891117Crossref (85) Polyvinyl alcohol (PVA) was matrix, deposited Pd-nanoparticles (Pd-TNSs) were incorporated it fabricate bio-orthogonally called PT-MNs, which precisely 15 × array conical shape, tip radius 10 μm, height 1,500 base diameter 500 center-to-center space 800 μm. uniform dispersion Pd-TNSs PVA matrix interfacial interactions between TNSs hydroxyl groups strengthen mechanical toughness patch, making easy penetrate skin minimally invasive manner be removed swelling vivo. Furthermore, three-dimensional needle swollen hydrogel accelerates N-(allyloxycarbonyl)-Doxorubicin (alloc-DOX), prodrug, Pd-TNSs. In vitro experiments proved alloc-DOX/PT-MN increased cell toxicity compared alloc-DOX. When vivo, PT-MN could fully inserted site acts activate production DOX situ intraperitoneal injection alloc-DOX, leading growth inhibition apoptosis. alloc-DOX instead parent significantly avoided toxic effects high doses, 3D structure not only restricted leakage plasma major organs, but also benefited diffusion activated tumors. modification increases possibility better tools anti-tumor paves way realizing inert small molecules agents tissues live animals. integrate Pd-TNs device, achieves insertion enhances spatially controlled restoration drug’s pharmacological property an alternative therapeutic strategy cancer contrast bio-liable converted metabolic or abnormalities tissues.6Rautio Meanwell N.A. Di L. Hageman M.J. expanding role contemporary design development.Nat. Drug Discov. 2018; 17: 559-587https://doi.org/10.1038/nrd.2018.46Crossref (268) greatly allows mitigation TM catalysis. other platforms such antibody engineering,7Rossin R. Versteegen R.M. Wu Khasanov Wessels H.J. Steenbergen E.J. Ten Hoeve W. Janssen H.M. van Onzen A.H.A.M. Hudson P.J. Robillard M.S. Chemically triggered release antibody-drug conjugate leads potent antitumour activity mice.Nat. Commun. 9: 1484https://doi.org/10.1038/s41467-018-03880-yCrossref click ligation reaction8Bilodeau D.A. Margison K.D. Serhan Pezacki J.P. Bioorthogonal Reactions Utilizing Nitrones Versatile Dipoles Cycloaddition Reactions.Chem. https://doi.org/10.1021/acs.chemrev.0c00832Crossref (14) immunotherapy.9Wang Gao Liu Guo S. Ma Tian Yang Immunogenic-cell-killing immunosuppression-inhibiting nanomedicine.Bioact. Mater. 6: 1513-1527https://doi.org/10.1016/j.bioactmat.2020.11.016Crossref (32) long term, realize vast versatility high-level entities.