A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression DOI Creative Commons
Marco Deiana, José María Andrés Castán, Pierre Josse

и другие.

Nucleic Acids Research, Год журнала: 2023, Номер 51(12), С. 6264 - 6285

Опубликована: Май 16, 2023

Abstract Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors exosomes, which are key components cancer cell proliferation. Moreover, purified exosomal DNA was recognized G4-specific antibody, thus highlighting presence such G4-forming sequences vesicles. Despite absence signal from nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering 3-fold increase nuclear G4 foci, slowing fork progression elevated levels both base damage, 8-oxoguanine, double-stranded breaks. Consequently, found to exert significant phototoxic effects (at nanomolar scale) toward lines tumor organoids. Furthermore, vivo testing reveals induces not only formation damage but also apoptosis zebrafish, specifically area where had accumulated. Collectively, approach shows promise for image-guided PDT.

Язык: Английский

Photo‐Responsive Hydrogel for Contactless Dressing Change to Attenuate Secondary Damage and Promote Diabetic Wound Healing DOI

Zi‐Yuan Li,

Xiaojie Zhang,

Yiming Gao

и другие.

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(17)

Опубликована: Март 3, 2023

Abstract Dressing change is a significant and inevitable process during wound healing. Possible secondary damage caused through dressing removal may impose great threat on recovery, thus resulting in healing delays ultimately higher cost of hospitalization. Hence, non‐contact refreshable with an ease operation desire, especially for chronic wounds where long‐term repeated would be performed. Herein, all‐light‐operated hydrogel that achieve fast remote‐controllable (30 s gelation/4 min dissolution upon light irradiation) presented. In diabetic murine model, substantially improved within 2–3 weeks observed due to attenuated changes. Moreover, promising facilitation the processes epithelialization, collagen deposition, cell proliferation, inflammatory regulation also detected, representing synergistic effect photo‐responsive therapeutic efficiency.

Язык: Английский

Процитировано

30

Synthetic molecular motor activates drug delivery from polymersomes DOI Creative Commons
Ainoa Guinart, Maria Korpidou, Daniel Doellerer

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(27)

Опубликована: Июнь 26, 2023

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with unsolved needs current molecular drug delivery. Here, we present a delivery system high spatiotemporal control and tunable release profiles. is based on combination an hydrophobic synthetic rotary motor PDMS-b-PMOXA diblock copolymer to create responsive self-assembled system. successful incorporation selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed trigger fluorescent dye efficiencies (up 75%). Moreover, proved ability turn off behavior demand over sequential cycles. Low concentrations photoresponsive units (down 1 mol% motor) are shown effectively promote release. Our was also tested under relevant physiological conditions using lung cancer cell line encapsulation Food Drug Administration (FDA)-approved drug. Similar levels viability observed compared free given showing potential our platform deliver functional drugs request efficiency. This work provides important step for application machines next generation smart systems.

Язык: Английский

Процитировано

30

Turning Red without Feeling Embarrassed─Xanthenium-Based Photocages for Red-Light-Activated Phototherapeutics DOI Creative Commons

Alexandra Egyed,

Krisztina Németh,

Tibor Á. Molnár

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 4026 - 4034

Опубликована: Фев. 8, 2023

Herein, we present high-yielding, concise access to a set of xanthenium-derived, water-soluble, low-molecular-weight photocages allowing light-controlled cargo release in the green red region. Very importantly, these new allow installation various payloads through ester, carbamate, or carbonate linkages even at last stage synthesis. Payloads were uncaged with high efficiency upon green, orange, light irradiation, leading carboxylic acids, phenols, and amines. The near-ideal properties carboxanthenium derivative further evaluated context drug using camptothecin-derived chemotherapeutic drug, SN38. Notably, caged showed orders magnitude lower cellulo, which was reinstated after irradiation. presented offer that facilitate translation photoactivated chemotherapy toward clinical applications.

Язык: Английский

Процитировано

29

Light‐Driven Self‐Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption DOI Open Access
Haoze Li,

Sensen Zhou,

Min Wu

и другие.

Advanced Materials, Год журнала: 2023, Номер 35(24)

Опубликована: Март 20, 2023

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due off-target effects and repeated dose toxicity of agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPNP ) herein reported for precise tumor disruption through two-stage light manipulation. SPNP consists as photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon first photoirradiation, administered vivo generates mild hyperthermia trigger hemorrhage, which activates coagulation cascade recruits more injured blood vessels. Such enhanced targeting enables intense destroy vasculature during second leading complete eradication efficient metastasis inhibition. Intriguingly, mechanism study reveals strategy alleviates splenomegaly reverses immunosuppressive microenvironment by reducing myeloid-derived suppressor cells. Therefore, not only illustrates light-driven self-recruitment enhance via single therapeutics but also deciphers immunotherapeutic role conducive studies.

Язык: Английский

Процитировано

26

A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression DOI Creative Commons
Marco Deiana, José María Andrés Castán, Pierre Josse

и другие.

Nucleic Acids Research, Год журнала: 2023, Номер 51(12), С. 6264 - 6285

Опубликована: Май 16, 2023

Abstract Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors exosomes, which are key components cancer cell proliferation. Moreover, purified exosomal DNA was recognized G4-specific antibody, thus highlighting presence such G4-forming sequences vesicles. Despite absence signal from nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering 3-fold increase nuclear G4 foci, slowing fork progression elevated levels both base damage, 8-oxoguanine, double-stranded breaks. Consequently, found to exert significant phototoxic effects (at nanomolar scale) toward lines tumor organoids. Furthermore, vivo testing reveals induces not only formation damage but also apoptosis zebrafish, specifically area where had accumulated. Collectively, approach shows promise for image-guided PDT.

Язык: Английский

Процитировано

26