Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release

Chen, Shuyi; Zhao, Xianrui; Chen, Jingyi; Chen, Jin; Kuznetsova, Larisa; Wong, Stanislaus S.; Ojima, Iwao

doi:10.1021/bc9005656

Cited by 311 publications

(287 citation statements)

References 44 publications

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“…46 Hcy-Mito and Hcy-Biot had the same reaction mechanisms except the targeting functions. The proposed reaction mechanism was illustrated in Scheme 1.…”

Section: Design Strategies For Probes Hcy-mito and Hcy-biotmentioning

confidence: 98%

Near-Infrared Fluorescence Probe for in Situ Detection of Superoxide Anion and Hydrogen Polysulfides in Mitochondrial Oxidative Stress

et al. 2016

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H 2 S plays important physiological and pathological roles in cardiovascular system and nervous system. But recent evidences imply that hydrogen polysulfides (H 2 S n ) are the actual signaling molecules in cells. Although H 2 S n have been demonstrated to be responsible for mediating tumor suppressors, ion channels, and transcription factors, more of their biological effects are still need to be elaborated. On one hand, H 2 S n have been suggested to be generated from endogenous H 2 S upon reaction with reactive oxygen species (ROS). On the other hand, H 2 S n derivatives are proposed to be a kind of direct antioxidant against intracellular oxidative stress. This conflicting results should be attributed to the regulation of redox homeostasis between ROS and H 2 S n . Superoxide anion (O 2 •− ) is undoubtedly the primary ROS existing in mitochondria. We reason that the balance of O 2•− and H 2 S n are pivotal in physiological and pathological processes. Herein, we report two near-infrared fluorescent probes Hcy-Mito and Hcy-Biot for the detection of O 2•− and H 2 S n in cells and in vivo. Hcy-Mito is conceived to be applied in mitochondria, and Hcy-Biot is designed to target tumor tissue. Both of the probes were successfully applied for visualizing exogenous and endogenous O 2•− and H 2 S n in living cells and in tumor mice models. The results demonstrate that H 2 S n can be promptly produced by mitochondrial oxidative stress. Flow cytometry assays for apoptosis suggest that H 2 S n play critical roles in antioxidant systems.

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“…46 Hcy-Mito and Hcy-Biot had the same reaction mechanisms except the targeting functions. The proposed reaction mechanism was illustrated in Scheme 1.…”

Section: Design Strategies For Probes Hcy-mito and Hcy-biotmentioning

confidence: 98%

Near-Infrared Fluorescence Probe for in Situ Detection of Superoxide Anion and Hydrogen Polysulfides in Mitochondrial Oxidative Stress

et al. 2016

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“…Ojima et al used biotin as a tumor targeting ligand in the design of theranostic agents utilizing different anticancer drugs and fluorophores. [196][197][198] The biotinylated fluorescein coupled with SB-T-1214 via the selfimmolative disulfide linker formed theranostic agent 59.…”

Section: Thiol-mediated Modesmentioning

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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“…118 A study demonstrated that modification of drug delivery with biotin is an effective pattern to enhance cell specificity against the cancer cells overexpressed with biotin receptors on the cell surfaces and to accelerate the internalization of the drug delivery into the targeted cancer cells through receptor-mediated endocytosis. 119 To verify the potential value of biotin for targeted liver neoplasms, Mishra and Jain 120 designed biotinmodified erythrocytes loaded with MTX by combining with N-hydroxysuccinimide ester of biotin. In vivo study showed that the MTX level of liver administrated with biotinylated erythrocytes was increased ~3-fold compared with free MTX and 1.8-fold compared with nonbiotinylated erythrocytes at 1 h after injection into rats, indicating that this drug system could be used to place hepatic arterial catheters for locoregional treatment of liver neoplasms.…”

mentioning

confidence: 99%