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The spatiotemporal control over the structure of nanoparticles while monitoring their localization in tumor cells can improve the precision of controlled drug release, thus enhancing the efficiency of drug delivery. Here, we report on a photochromic nanoparticle system ( LSNP ), assembled from fluorescent bistable hydrazone photoswitch-modified amphiphilic copolymers. The intrinsic emission of the hydrazone switch allows for the visualization of particle uptake, as well as their intracellular distribution. The Z → E photoswitching of the hydrazone switch within the nanoparticle leads to the expansion of the nanoparticles ( i.e. , drug release) accompanied by emission quenching, the degree of which can function as an internal indicator for the amount of drug released. The bistability of the switch enables the kinetic trapping of particles of different sizes as a function of irradiation time, and allows for the exhibition of light-dependent cell cytotoxicity in MDA-MB-231 cells using LSNP loaded with doxorubicin.
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DNA Functionality with Photoswitchable Hydrazone Cytidine
A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into oligodeoxynucleotides to construct photoswitchable DNA strands. The E-Z isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by 1H NMR and HPLC in the contexts of both nucleoside and oligodeoxynucleotides. The light activated Z form isomer of this hydrazone-cytidine with a six-member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by using Bst DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting the potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that have potential chemical biology and bio-medicinal applications to control DNA synthesis and DNA-enzyme interactions using cell friendly blue light irradiation.
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- Award ID(s):
- 1715234
- PAR ID:
- 10223804
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/chem.202100742
