An excipient-free “sugar-coated bullet” for the targeted treatment of orthotopic hepatocellular carcinoma

Feiyang, 涛 易; Lingyan, 涛 易; Liu, Dongya; Wei, Peng; Feng, Wei; Yi, Tao

doi:10.1039/d2sc03365h

Cited by 11 publications

(4 citation statements)

References 53 publications

(61 reference statements)

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“…), resulting in a selective anticancer effect. [12][13][14][15][16][17][18][19][20][21] Glutathione (GSH) has a concentration of 2-10 mM in cancer cells, which is higher than in normal cells, making it favorable as an activator for selective chemotherapy. Most of the reported GSH-activated prodrugs use disulfide bonds as reactive linkers (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%

“…In general, such systems can be activated by tumor‐specific microenvironments (such as pH, reactive oxygen species (ROS), overexpressed enzymes, etc. ), resulting in a selective anticancer effect [12–21] . Glutathione (GSH) has a concentration of 2–10 mM in cancer cells, which is higher than in normal cells, making it favorable as an activator for selective chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy

Wang,

Pan,

et al. 2024

Smart Molecules

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Glutathione (GSH)‐activated prodrugs are promising for overcoming the limitations of conventional anti‐tumor drugs. However, current GSH‐responsive disulfide groups exhibit unregulated reactivity, making it impossible to precisely control the drug release rate. We herein report a series of GSH‐responsive prodrugs with a “three‐in‐one” molecular design by integrating a fluorescence report unit, stimuli‐responsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution (SNAr) reactivity. The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron‐withdrawing or ‐donating abilities on the BODIPY core. Furthermore, the prodrugs self‐assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy (PDT). The PDT process also increases the concentration of GSH in cells, further promoting the release of drugs for chemotherapy. This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy

Wang,

Pan,

et al. 2024

Smart Molecules

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“…Cancer remains a significant global health challenge, with traditional chemotherapy and radiotherapy showing limitations in terms of safety and efficacy, often accompanied by severe side effects [1][2][3]. Researchers have explored non-invasive approaches such as near-infrared (NIR) and ultrasound (US) for cancer treatment in pursuit of novel therapeutic modalities [4][5][6]. While NIR has limited penetration depth, ultrasound offers deeper tumor penetration capabilities, making it suitable for treating deepseated tumors [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Glutathione and acid dual-responsive bismuth-based nanosensitizer for chemo-mediated cancer sonodynamic therapy

Chen,

Ping,

et al. 2024

Biomed. Mater.

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Chemotherapeutic agents hold significant clinical potential in combating tumors. However, delivering these drugs to the tumor site for controlled release remains a crucial challenge. In this study, we synthesize and construct a glutathione (GSH) and acid dual-responsive bismuth-based nano-delivery platform (BOD), aiming for sonodynamic enhancement of docetaxel (DTX)-mediated tumor therapy. The bismuth nanomaterial can generate multiple reactive oxygen species under ultrasound stimulation. Furthermore, the loading of DTX to form BOD effectively reduces the toxicity of DTX in the bloodstream, ensuring its cytotoxic effect is predominantly exerted at the tumor site. DTX can be well released in high expression of GSH and acidic tumor microenvironment. Meanwhile, ultrasound can also promote the release of DTX. Results from both in vitro and in vivo experiments substantiate that the synergistic therapy involving chemotherapy and sonodynamic therapy significantly inhibits the growth and proliferation of tumor cells. This study provides a favorable paradigm for developing a synergistic tumor treatment platform for tumor microenvironment response and ultrasound-promoted drug release.

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“…In our previous studies, we have successfully developed a series of HOCl-specific fluorescent probes using methylene blue (MB) structure and utilized them to investigate the presence of HOCl in diverse conditions such as the arthritis 36 , tumor microenvironment 37 - 39 , psoriasis 40 , and other diseases 41 - 43 . Herein, we designed and synthesized a fluorescent probe DHU-CBA1 by attachment of IBP (ibuprofen, a nonsteroidal anti-inflammatory drug) and MB.…”

Section: Introductionmentioning

confidence: 99%

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics

Lu,

Wei,

Peng

et al. 2024

Theranostics

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Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro . Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

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An excipient-free “sugar-coated bullet” for the targeted treatment of orthotopic hepatocellular carcinoma

Abstract: Several components of traditional nanoformulations that result in structural heterogeneity, poor reproducibility, excipient-trigged biotoxicity, and low retention of antitumor drugs in neoplastic foci are important barriers limiting clinical translation. We...

Cited by 11 publications

References 53 publications

Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy

Activatable theranostic prodrug scaffold with tunable drug release rate for sequential photodynamic and chemotherapy

Glutathione and acid dual-responsive bismuth-based nanosensitizer for chemo-mediated cancer sonodynamic therapy

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics

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