Harnessing Cyanine Reactivity for Optical Imaging and Drug Delivery

Accounts of Chemical Research, Год журнала: 2018, Номер 51(12), С. 3226 - 3235

Опубликована: Ноя. 12, 2018

ConspectusOptical approaches that visualize and manipulate biological processes have transformed modern biomedical research. An enduring challenge is to translate these powerful methods into increasingly complex physiological settings. Longer wavelengths, typically in the near-infrared (NIR) range (∼650–900 nm), can enable advances both fundamental clinical settings; however, suitable probe molecules are needed. The pentamethine heptamethine cyanines, led by prototypes Cy5 Cy7, among most useful compounds for fluorescence-based applications, finding broad use a of contexts. defining chemical feature molecules, key chromophoric element, an odd-numbered polymethine links two nitrogen atoms. Not only light-harvesting functional group, cyanine chromophore subject thermal photochemical reactions dramatically alter many properties molecules.This Account describes our recent studies define intrinsic reactivity. hypothesis driving this research novel chemistries be used address challenging problems areas imaging drug delivery. We first review reaction discovery efforts seek limitations long-wavelength fluorophores: undesired thiol reactivity modest fluorescence quantum yield. Heptamethine cyanines with O-alkyl substituent at central C4′ carbon were prepared through N- O-transposition reaction. Unlike commonly C4′-phenol variants, new class fluorophores resistant modification exhibits improved vivo when as antibody tags. also developed strategy enhance yield far-red cyanines. Using synthetic involving cross metathesis/tetracyclization sequence, approach conformationally restrains scaffold. resulting exhibit enhanced (ΦF = 0.69 vs ΦF 0.15). Furthermore, conformational restraint improves interconversion between reduced hydrocyanine intact forms, which enables super resolution microscopy.This then highlights NIR photocaging. Our involves deliberate photooxidation, previously associated photodegradation. uncaging sequence initiated photooxidative cleavage (using wavelengths up 780 prompts C–N bond hydrolysis/cyclization phenol liberation. This has been applied generate NIR-activated antibody-drug conjugates. Tumor uptake monitored using fluorescence, prior external irradiation source. slow tumor progression increase survival MDA-MB-468-luc mouse model. Broadly, vantage point providing auspicious features delivery

Язык: Английский

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NIR-light-mediated spatially selective triggering of anti-tumor immunity via upconversion nanoparticle-based immunodevices

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Июнь 28, 2019

Abstract Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses superior spatiotemporal precision enhanced safety urgently needed. Here we report an activatable engineered immunodevice that enables remote control over antitumor immunity in vitro vivo near-infrared (NIR) light. The composed rationally designed UV light-activatable immunostimulatory agent upconversion nanoparticle, which acts as transducer shift light sensitivity device NIR window. controlled regulation allows generation effective response within tumor without disturbing elsewhere body, thereby maintaining efficacy while mitigating systemic toxicity. present work illustrates potential remote-controlled triggering immunoactivity at right time site.

Язык: Английский

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An orthogonally regulatable DNA nanodevice for spatiotemporally controlled biorecognition and tumor treatment

Science Advances, Год журнала: 2020, Номер 6(25)

Опубликована: Июнь 17, 2020

Despite the potential of nanodevices for intelligent drug delivery, it remains challenging to develop controllable therapeutic devices with high spatial-temporal selectivity. Here, we report a DNA nanodevice that can achieve tumor recognition and treatment improved spatiotemporal precision under regulation orthogonal near-infrared (NIR) light. The is built by combining an ultraviolet (UV) light-activatable aptamer module photosensitizer (PS) up-conversion nanoparticle (UCNP) enables operation deep tissue-penetrable NIR UCNPs convert two distinct excitations into UV green emissions programmable photoactivation modules PSs, respectively, allowing spatiotemporally controlled target photodynamic antitumor effect. Furthermore, when combined immune checkpoint blockade therapy, results in regression untreated distant tumors. This work provides new approach diagnostic activity at right time place.

Язык: Английский

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Visible Light-Initiated Bioorthogonal Photoclick Cycloaddition

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(44), С. 14542 - 14546

Опубликована: Окт. 23, 2018

Here we report a visible light-triggered, catalyst free bioorthogonal reaction that proceeds via distinct pathway from reported reactions. The prototype of this was the photocycloaddition 9,10-phenanthrenequinone with electron-rich alkenes to form fluorogenic [4+2] cycloadducts. photoclick cycloaddition readily initiated using conventional light source such as hand-held LED lamp. proceeded rapidly under biocompatible conditions, without observable competition side reactions nucleophilic additions by water or common species. functionality in did not cross react various alkynes and electron-deficient monomethyl fumarate. We demonstrated orthogonal labeling two proteins together strain promoting azide–alkyne click UV-triggered tetrazole application temporal spatial live cells also demonstrated.

Язык: Английский

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Selective Modification of Tryptophan Residues in Peptides and Proteins Using a Biomimetic Electron Transfer Process

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(20), С. 9112 - 9118

Опубликована: Апрель 29, 2020

We report here a photochemical process for the selective modification of tryptophan (Trp) residues in peptides and small proteins using electron-responsive N-carbamoylpyridinium salts UV-B light. Preliminary mechanistic experiments suggest that photoconjugation proceeds through photoinduced electron transfer (PET) between Trp pyridinium salt, followed by fragmentation N-N bond concomitant this group to Trp. The reaction displays excellent site selectivity is tolerant other, redox-active amino-acid residues. Moreover, pure aqueous conditions without requirement organic cosolvents or photocatalysts, enhanced glutathione, operates efficiently over wide range peptide concentrations (10-700 μM). scope was explored labeling 6-Trp-containing ranging from 1 14 kDa. demonstrate versatility salt both tuning electrochemical properties scaffold enable challenging reactions carbamoyl moiety tether plethora productive functional groups, including reactive handles, purification tags, removable protecting groups.

Язык: Английский

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Nucleic Acids Analysis

Science China Chemistry, Год журнала: 2020, Номер 64(2), С. 171 - 203

Опубликована: Дек. 2, 2020

Язык: Английский

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Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Фев. 22, 2019

Manipulation of neuronal activity using two-photon excitation azobenzene photoswitches with near-infrared light has been recently demonstrated, but their practical use in tissue to photostimulate individual neurons three-dimensional precision hampered by firstly, the low efficacy and reliability NIR-induced photoisomerization compared one-photon excitation, secondly, short cis state lifetime responsive azo switches. Here we report rational design based on theoretical calculations synthesis endowed both high absorption cross section slow thermal back-isomerization. These compounds provide optimized sustained stimulation light-scattering brain Caenorhabditis elegans nematodes, displaying photoresponse intensities that are comparable those achieved under excitation. This finding opens way genetically targeted pharmacologically selective dissect intact circuits three dimensions.

Язык: Английский

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General Principles for the Design of Visible‐Light‐Responsive Photoswitches: Tetra‐ortho‐Chloro‐Azobenzenes

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(48), С. 21663 - 21670

Опубликована: Авг. 28, 2020

Molecular photoswitches enable reversible external control of biological systems, nanomachines, and smart materials. Their development is driven by the need for low energy (green-red-NIR) light switching, to allow non-invasive operation with deep tissue penetration. The lack clear design principles adaptation optimization such systems limits further applications. Here we provide a rulebook tetra-ortho-chloroazobenzenes, an emerging class visible-light-responsive photochromes, elucidating role that substituents play in defining their key characteristics: absorption spectra, band overlap, photoswitching efficiencies, half-lives unstable cis isomers. This achieved through joint photochemical theoretical analyses representative library molecules featuring varying electronic nature. A set guidelines presented enables tuning properties desired application informed photochrome engineering.

Язык: Английский

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Recent advances in the optical control of protein function through genetic code expansion

Current Opinion in Chemical Biology, Год журнала: 2018, Номер 46, С. 99 - 107

Опубликована: Июль 26, 2018

Язык: Английский

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Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(46), С. 15764 - 15773

Опубликована: Окт. 10, 2018

The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over cytotoxic activity would allow improving chemotherapy treatments, light-regulated drugs well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor human dihydrofolate reductase (DHFR), as a photochromic analogue methotrexate, widely prescribed chemotherapeutic drug treat cancer psoriasis. Quantification DHFR enzymatic activity, cell proliferation, in vivo effects zebrafish show that phototrexate behaves potent antifolate its photoactivated cis configuration it is nearly inactive dark-relaxed trans form. Thus, constitutes proof-of-concept design small molecules step forward develop targeted photochemotherapies with localized reduced adverse

Язык: Английский

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