Dual-targeted 5-aminolevulinic acid derivatives with glutathione depletion function for enhanced photodynamic therapy

Li, Ke; Dong, Wenyi; Miao, Yinxing; Liu, Qingzhu; Qiu, Ling; Lin, Jianguo

doi:10.1016/j.jphotobiol.2020.112107

Cited by 11 publications

(4 citation statements)

References 40 publications

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“…In Vitro Cytotoxicity Assay: HeLa cells were seeded in 96-well plates at a density of 1 × 10 4 cells per well. After attachment for 24 h, the cells were treated with or without DEM (1 mm) or GSH-OEt (5 mm) for 2 h, [45,46] followed by 200 μL of fresh medium containing free ARV-771 and ARV@PDSA at a concentration of 1000 nm ARV-771 for 24 h. In terms of concentration-dependent cytotoxicity, the seeded HeLa cells or B16F10 cells were incubated with free ARV-771 or ARV@PDSA at the concentrations of 0, 50, 100, 200, 500, and 1000 nm ARV-771 for 24 h. Then, 10 μL of MTT solution (5 mg mL −1 ) was added to each well followed by incubation for another 4 h. Finally, the medium was replaced by 100 μL of DMSO. The absorbance of the DMSO solutions in each well was measured at 570 nm using a microplate reader (TECAN, Infinite M Plex).…”

Section: Methodsmentioning

confidence: 99%

Glutathione‐Scavenging Nanoparticle‐Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

Liu

Chen

et al. 2023

Advanced Science

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PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins.

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Section: Methodsmentioning

confidence: 99%

Glutathione‐Scavenging Nanoparticle‐Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

Liu

Chen

et al. 2023

Advanced Science

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“…With 5-ALA for PDT and doxorubicin (DOX) as a chemo drug, the "Trojan Horse" nanogel shows effective response against the 4T1 cancer cell line. For glutathione depletion, Li et al used dual-targeted 5-ALA for enhanced PDT [50]. By using ALA methyl ester (OMe), which can be metabolized to PpIX inside the cells, the combination of dual targeting with PDT provides enhanced cancer therapeutic efficacy.…”

Section: Porfimer Sodium (Photofrin)mentioning

confidence: 99%

Photosensitizer-Functionalized Nanocomposites for Light-Activated Cancer Theranostics

Dash

Das

Chen

2021

IJMS

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Photosensitizers (PSs) have received significant attention recently in cancer treatment due to its theranostic capability for imaging and phototherapy. These PSs are highly responsive to light source of a suitable wavelength for image-guided cancer therapy from generated singlet oxygen and/or thermal heat. Various organic dye PSs show tremendous attenuation of tumor cells during cancer treatment. Among them, porphyrin and chlorophyll-based ultraviolet-visible (UV-Vis) dyes are employed for photodynamic therapy (PDT) by reactive oxygen species (ROS) and free radicals generated with 400–700 nm laser lights, which have poor tissue penetration depth. To enhance the efficacy of PDT, other light sources such as red light laser and X-ray have been suggested; nonetheless, it is still a challenging task to improve the light penetration depth for deep tumor treatment. To overcome this deficiency, near infrared (NIR) (700–900 nm) PSs, indocyanine green (ICG), and its derivatives like IR780, IR806 and IR820, have been introduced for imaging and phototherapy. These NIR PSs have been used in various cancer treatment modality by combining photothermal therapy (PTT) and/or PDT with chemotherapy or immunotherapy. In this review, we will focus on the use of different PSs showing photothermal/photodynamic response to UV-Vis or NIR-Vis light. The emphasis is a comprehensive review of recent smart design of PS-loaded nanocomposites for targeted delivery of PSs in light-activated combination cancer therapy.

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“…However, tumor cells contain abundant GSH, which can weaken the efficiency of PDT by clearing ROS, thus limiting the effect of PDT combined with PTT. − In PDT, the most influential factor on the therapeutic effect is the produced GSH, which has the most significant impact on ROS. Therefore, consuming the overexpressed GSH within cells can effectively improve the efficacy of PDT. − The basic principle of PTT is that photothermal agents (PTAs) absorb specific wavelength light and convert the photonic energy into thermal energy to ablate tumor cells . Heat shock proteins (HSPs) are molecular chaperones that play an important role in maintaining correct protein expression, cell growth, and development.…”

Section: Introductionmentioning

confidence: 99%

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors

Deng,

Li,

Pan

et al. 2024

ACS Appl. Mater. Interfaces

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Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.

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Dual-targeted 5-aminolevulinic acid derivatives with glutathione depletion function for enhanced photodynamic therapy

Cited by 11 publications

References 40 publications

Glutathione‐Scavenging Nanoparticle‐Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

Glutathione‐Scavenging Nanoparticle‐Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

Photosensitizer-Functionalized Nanocomposites for Light-Activated Cancer Theranostics

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors

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