A molecular dyad delivered by biodegradable polymeric nanoparticles for combined PDT and NO-PDT in cancer cells

Parisi, Cristina; Longobardi, Giuseppe; Graziano, Adriana Carol Eleonora; Fraix, Aurore; Conte, Claudia; Quaglia, Fabiana; Sortino, Salvatore

doi:10.1016/j.bioorg.2022.106050

Cited by 11 publications

(13 citation statements)

References 36 publications

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“…Such a reduction is not surprising. A similar effect was noted for other long-lived triplets embedded in the same type of polymeric NPs 30 and, according to the literature, is typically attributable to a shielding effect by host nanocarriers from the external environment, especially from molecular oxygen. 32 Based on these results and the concentration values of NBF-NO and O 2 , the quenching of the triplet state by the former largely dominates over the latter, making the NO photorelease process under aerobic conditions almost as effective as under hypoxic conditions.…”

Section: ■ Results and Discussionmentioning

confidence: 85%

“…mPEG-b-PCL is expected to provide more or less ordered core-shell structures with a PCL core surrounded by PEG chains depending on the polymer hydrophilic/lipophilic balance and experimental conditions adopted to form NPs. These NPs are well dispersible in water, 30 show excellent optical transparency, which is ideal for spectroscopic investigations, and represent suitable host nanocarriers to solubilize both NBF-NO and VTP, which are insoluble in an aqueous medium.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

et al. 2023

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The role of nitric oxide (NO) as an "unconventional" therapeutic and the strict dependence of biological effects on its concentration require the generation of NO with precise spatiotemporal control. The development of precursors and strategies to activate NO release by excitation in the so-called "therapeutic window" with highly biocompatible and tissue-penetrating red light is desirable and challenging. Herein, we demonstrate that one-photon red-light excitation of Verteporfin, a clinically approved photosensitizer (PS) for photodynamic therapy, activates NO release, in a catalytic fashion, from an otherwise blue-light activatable NO photodonor (NOPD) with an improvement of about 300 nm toward longer and more biocompatible wavelengths. Steady-state and time-resolved spectroscopic and photochemical studies combined with theoretical calculations account for an NO photorelease photosensitized by the lowest triplet state of the PS. In view of biological applications, the water-insoluble PS and NOPD have been co-entrapped within water-dispersible, biodegradable polymeric nanoparticles (NPs) of mPEG-b-PCL (about 84 nm in diameter), where the red-light activation of NO release takes place even more effectively than in an organic solvent solution and almost independently by the presence of oxygen. Moreover, the ideal spectroscopic prerequisites and the restricted environment of the NPs permit the green-fluorescent co-product formed concomitantly to NO photorelease to communicate with the PS via Forster resonance energy transfer. This leads to an enhancement of the typical red emission of the PS offering the possibility of a double color optical reporter useful for the real-time monitoring of the NO release through fluorescence techniques. The suitability of this strategy applied to the polymeric NPs as potential nanotherapeutics was evaluated through biological tests performed by using HepG2 hepatocarcinoma and A375 melanoma cancer cell lines. Fluorescence investigation in cells and cell viability experiments demonstrates the occurrence of the NO release under onephoton red-light illumination also in the biological environment. This confirms that the adopted strategy provides a valuable tool for generating NO from an already available NOPD, otherwise activatable with the poorly biocompatible blue light, without requiring any chemical modification and the use of sophisticated irradiation sources.

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Section: ■ Results and Discussionmentioning

confidence: 85%

Section: ■ Results and Discussionmentioning

confidence: 99%

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

et al. 2023

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“…As detailed above, although it was possible to enable the activation of NBDNO via a metal‐free photoredox catalysis mechanism in organic solvents under NIR irradiation, it would be more intriguing to enable this platform to work under physiological conditions. Unfortunately, NBDNO was not stable in aqueous media and spontaneous hydrolysis was observed, greatly hampering its biomedical applications (Figure S24) [14] . To overcome this drawback, amphiphilic diblock copolymers of PNO and PNH were synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization of 2‐isocyanatoethyl methacrylate using a poly(ethylene glycol) macroRAFT agent, followed by modification of the isocyanate groups in the side chains with NBDNO / NBDNH precursors (Scheme 1d).…”

Section: Resultsmentioning

confidence: 99%

“…Unfortunately, NBDNO was not stable in aqueous media and spontaneous hydrolysis was observed, greatly hampering its biomedical applications (Figure S24). [14] To overcome this drawback, amphiphilic Angewandte Chemie diblock copolymers of PNO and PNH were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-isocyanatoethyl methacrylate using a poly(ethylene glycol) macroRAFT agent, followed by modification of the isocyanate groups in the side chains with NBDNO/NBDNH precursors (Scheme 1d). We surmised that the self-assembly of PNO copolymers into micellar nanoparticles may efficiently inhibit the spontaneous hydrolysis of NBDNO moieties.…”

Section: Nir-mediated Onoo à Release In Aqueous Solutionsmentioning

confidence: 99%

Overcoming the Oxygen Dilemma in Photoredox Catalysis: Near‐Infrared (NIR) Light‐Triggered Peroxynitrite Generation for Antibacterial Applications

et al. 2023

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The peroxynitrite anion (ONOO−) is closely associated with many diseases and the creation of ONOO− donors is an essential means of understanding its pathophysiological functions. However, it is challenging to develop ONOO− donors due to the difficulties in simultaneously producing highly reactive and short‐lived nitric oxide (NO) and superoxide anion (O2⋅−). Here, we report a novel strategy for constructing ONOO− donors by combining near‐infrared (NIR)‐mediated type I photosensitization and photoredox catalysis. The key design using a Nile blue analogue that can serve as both a type I photosensitizer and a metal‐free photocatalyst. Intriguingly, the formation of O2⋅− via type I photosensitization avoids oxygen interference and instead activates nitrobenzofurazan‐based NO donors via oxygen‐tolerant NIR photoredox catalysis. The simultaneous release of O2⋅− and NO leads to ONOO− release, showing both antibacterial and antibiofilm activities.

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“…Unfortunately, NBDNO was not stable in aqueous media and spontaneous hydrolysis was observed, greatly hampering its biomedical applications (Figure S24). [14] To overcome this drawback, amphiphilic Angewandte Chemie Forschungsartikel diblock copolymers of PNO and PNH were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-isocyanatoethyl methacrylate using a poly(ethylene glycol) macroRAFT agent, followed by modification of the isocyanate groups in the side chains with NBDNO/NBDNH precursors (Scheme 1d). We surmised that the self-assembly of PNO copolymers into micellar nanoparticles may efficiently inhibit the spontaneous hydrolysis of NBDNO moieties.…”

Section: Nir-mediated Onoo à Release In Aqueous Solutionsmentioning

confidence: 99%

Overcoming the Oxygen Dilemma in Photoredox Catalysis: Near‐Infrared (NIR) Light‐Triggered Peroxynitrite Generation for Antibacterial Applications

et al. 2023

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A molecular dyad delivered by biodegradable polymeric nanoparticles for combined PDT and NO-PDT in cancer cells

Cited by 11 publications

References 36 publications

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles

Overcoming the Oxygen Dilemma in Photoredox Catalysis: Near‐Infrared (NIR) Light‐Triggered Peroxynitrite Generation for Antibacterial Applications

Overcoming the Oxygen Dilemma in Photoredox Catalysis: Near‐Infrared (NIR) Light‐Triggered Peroxynitrite Generation for Antibacterial Applications

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