A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

Garland, Megan; Yim, Joshua J.; Bogyo, Matthew

doi:10.1016/j.chembiol.2015.12.003

Cited by 217 publications

(196 citation statements)

References 100 publications

(143 reference statements)

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“…This is particularly true as newer target probes are being developed to enhance tumor specificity. 87 In fact, a number of studies have continued to experience suboptimal development in preclinical models and poor funding for probe synthesis, toxicity and safety studies, and subsequent translation to phase I clinical trials. 55 Furthermore, the regulatory approval of both imaging agents and devices is cumbersome, complex, and can significantly slow the process of developing multicenter phase III clinical trials.…”

Section: Common Challenges Pitfalls and Setbacksmentioning

confidence: 99%

Oncologic Procedures Amenable to Fluorescence-guided Surgery

et al. 2017

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Objective: Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type. Background: For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye. Methods: We performed a systematic review of clinicatrials.gov using search terms ‘‘fluorescence,’’ ‘‘image-guided surgery,’’ and ‘‘near-infrared imaging’’ to identify trials utilizing FGS for those received on or before May 2016. Inclusion criteria: fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases. Exclusion criteria: fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence. Results: Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision. Conclusions: The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.

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Section: Common Challenges Pitfalls and Setbacksmentioning

confidence: 99%

Oncologic Procedures Amenable to Fluorescence-guided Surgery

et al. 2017

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“…42,43 Compared with nanoparticle-based therapeutic agents, small molecular fluorescent probe-based therapeutic agents are becoming preferred chemotherapeutic candidates. 3,[44][45][46][47][48][49][50] These small fluorescent theranostic agents exhibit improved photophysical properties and can be easily modified by chemical synthesis. 51,52 The structural architecture of these systems is often relatively simple and compact: a desirable fluorophore, a tumor targeting ligand, and a masked antitumor drug.…”

Section: Jaebum Choomentioning

confidence: 99%

“…153 The molecular targets of CTX include a lipid raftanchored complex that contains matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, the transmembrane inhibitor of MMP-2, the glioma-specific chloride ion channel, and the ClC-3 chloride ion channel. 44 For intraoperative differentiation of tumor margins or small foci of cancer cells, Olson et al developed a molecular imaging conjugate composed of CTX and Cy5.5. 154 The probe could delineate malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue.…”

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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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“…[1][2][3] The power of such imaging methods has led to increased interest in identifying new types of dyes, opticallyactive materials, and nanoparticles that have enhanced photophysical properties suitable for multimodal, multiplexed, and super-resolution imaging. [4][5][6][7][8][9][10][11][12][13][14] Because fluorophores play such a critical role in understanding biological processes, it is somewhat surprising that most advances in small molecule dye technology today rely on structural modifications of scaffolds discovered over a century ago.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Chemical Space of Biocompatible Fluorophores: Nanohoops in Cells

White¹,

Yu²,

Kawashima³

et al. 2018

Preprint

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Abstract:The design and optimization of fluorescent molecules has driven the ability to interrogate complex biological events in real time. Notably, most advances in bioimaging fluorophores are based on optimization of core structures that have been known for over a century. Recently, new synthetic methods have resulted in an explosion of non-planar conjugated macrocyclic molecules with unique optical properties yet to be harnessed in a biological context. Herein we report the synthesis of the first aqueous-soluble carbon nanohoop (i.e. a macrocyclic slice of a carbon nanotube prepared via organic synthesis) and demonstrate its bioimaging capabilities in live cells. This work establishes the nanohoops as an exciting new class of macrocyclic fluorophores poised for further development as novel bioimaging tools.

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A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

Cited by 217 publications

References 100 publications

Oncologic Procedures Amenable to Fluorescence-guided Surgery

Oncologic Procedures Amenable to Fluorescence-guided Surgery

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

Expanding the Chemical Space of Biocompatible Fluorophores: Nanohoops in Cells

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