Site-Specific and Far-Red-Light-Activatable Prodrug of Combretastatin A-4 Using Photo-Unclick Chemistry

Bio, Moses; Rajaputra, Pallavi; Nkepang, Gregory; Awuah, Samuel G.; Hossion, Abugafar M. L.; You, Youngjae

doi:10.1021/jm400139w

Cited by 87 publications

(91 citation statements)

References 26 publications

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“…The same rational was adopted by You groups to develop NIR‐responsive ROS‐activable prodrugs 96. The prodrug is comprised of a phorphyrin derivative, a 1 O 2 ‐responsive aminoarylate linker and a combretastatin A‐4, a natural anticancer drug inhibiting tubulin polymerization.…”

Section: Ros‐activatable Prodrugsmentioning

confidence: 99%

Reactive‐Oxygen‐Species‐Responsive Drug Delivery Systems: Promises and Challenges

2016

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Given the increasing evidence indicates that many pathological conditions are associated with elevated reactive oxygen species (ROS) levels, there have been growing research efforts focused on the development of ROS‐responsive carrier systems because of their promising potential to realize more specific diagnosis and effective therapy. By judicious utilization of ROS‐responsive functional moieties, a wide range of carrier systems has been designed for ROS‐mediated drug delivery. In this review article, insights into design principle and recent advances on the development of ROS‐responsive carrier systems for drug delivery applications are provided alongside discussion of their in vitro and in vivo evaluation. In particular, the discussions in this article will mainly focus on polymeric nanoparticles, hydrogels, inorganic nanoparticles, and activatable prodrugs that have been integrated with diverse ROS‐responsive moieties for spatiotemporally controlled release of drugs for effective therapy.

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Section: Ros‐activatable Prodrugsmentioning

confidence: 99%

Reactive‐Oxygen‐Species‐Responsive Drug Delivery Systems: Promises and Challenges

2016

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“…You et al demonstrated that the aminoacrylate group could be cleaved to release parent drugs after oxidation by 1 O 2 when activated by NIR light. 233 The prodrugs of combretastatin A-4 (87a-c) contain core-modified porphyrin as a NIR photosensitizer to generate 1 O 2 . The aminoacrylate linker of 87a was broken by tissue-penetrable NIR light (690 nm), releasing the antitumor drug.…”

Section: à2mentioning

confidence: 99%

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

et al. 2017

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Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells. Advances in in vivo medical imaging for visualizing tumor lesions can aid diagnosis, facilitate surgical resection, investigate therapeutic efficacy, and improve prognosis. In particular, the modality of fluorescence imaging has high specificity and sensitivity and has been utilized for medical imaging. Therefore, there are great opportunities for chemists and physicians to conceive, synthesize, and exploit new chemical probes that can image tumors and release chemotherapy drugs in vivo. This review focuses on small molecular ligand-targeted fluorescent imaging probes and fluorescent theranostics, including their design strategies and applications in clinical tumor treatment. The progress in chemical probes described here suggests that fluorescence imaging is a vital and rapidly developing field for interventional surgical imaging, as well as tumor diagnosis and therapy.

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“…Our study of various singlet oxygen-cleavable linkers led to the discovery of an efficient aminoacrylate linker. 44, 45 Utilizing this aminoacrylate linker, our group prepared conjugates of model drugs, including combretastatin-A4 (CA4) 41–43 and SN-38. 40 Both of these compounds have a phenolic group and effectively released parent drugs with visible or far-red light illumination.…”

Section: Introductionmentioning

confidence: 99%

Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy

et al. 2016

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Paclitaxel (PTX) is one of the most useful chemotherapeutic agents approved for several cancers, including ovarian, breast, pancreatic, and non-small cell lung cancer. However, it causes systemic side effects when administered parenterally. Photodynamic therapy (PDT) is a new strategy for treating local cancers using light and photosensitizer. Unfortunately, PDT is often followed by recurrence, due to incomplete ablation of tumors. To overcome these problems, we prepared the far-red light-activatable prodrug of PTX by conjugating photosensitizer via singlet oxygen-cleavable aminoacrylate linker. Tubulin polymerization enhancement and cytotoxicity of prodrugs were dramatically reduced. However, once illuminated with far-red light, the prodrug effectively killed SKOV-3 ovarian cancer cells through the combined effects of PDT and locally released PTX. Ours is the first PTX prodrug that can be activated by singlet oxygen using tissue penetrable and clinically useful far-red light, which kills the cancer cells through the combined effects of PDT and site-specific PTX chemotherapy.

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Site-Specific and Far-Red-Light-Activatable Prodrug of Combretastatin A-4 Using Photo-Unclick Chemistry

Cited by 87 publications

References 26 publications

Reactive‐Oxygen‐Species‐Responsive Drug Delivery Systems: Promises and Challenges

Reactive‐Oxygen‐Species‐Responsive Drug Delivery Systems: Promises and Challenges

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy

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