ReviewMolecularly near-infrared fluorescent theranostics for in vivo tracking tumor-specific chemotherapy
Graphical abstract
In this review, we summary the design concepts and strategies of NIR fluorescent theranostics for the sense-release in living systems. In particular, molecularly NIR fluorescent theranostic prodrug is elucidated to address current challenges of real-time bioimaging and tumor-specific chemotherapy for personalized treatment.
Introduction
Theranostic is defined as a material that combines both diagnostic and therapeutic functions [[1], [2], [3], [4], [5]]. Molecularly theranostics based strategy can simultaneously realize the therapy with diagnostic information in a single-entity platform and evaluate in real-time the prognosis after therapy [[6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]]. Indeed, molecular imaging serves this diagnostic function and provides powerful means for specific molecular information on the presence of defined molecular targets before, during, and after therapy [20]. There has been an explosive development in the design of molecular imaging contrasts and imaging-guided therapeutics [21]. To date, a number of near-infrared (NIR) fluorescent probes have been developed for tracing molecular processes in vitro and in vivo [[22], [23], [24], [25]]. In particular, molecularly NIR fluorescent prodrugs that enabling in vivo imaging and therapeutic chemotherapy (sense-and-release) have received considerable attention to diagnose and treat cancer [26].
NIR fluorescence light (650–900 nm) has been widely utilized in clinical imaging by providing surgeons highly specific images of target tissue [[27], [28], [29], [30], [31]]. Compared with the visible emission, NIR emission possesses unique advantages including minimized interfere of auto-fluorescence, deep tissues penetration, and less damage to biological samples [[32], [33], [34], [35], [36]]. In molecular theranostics, NIR fluorescence is a preferential way for real-time tracking sense-and-release, enabling intelligent recognition and then releasing optimal dosages of anticancer drugs for specific therapy.
In this review, we summarized the design strategies of NIR fluorescent theranostics prodrugs for the sense-and-release of tumor-specific chemotherapy in Scheme 1, including OFF-ON pattern based NIR theranostics, dual-channel pattern based NIR theranostics, physically encapsulated NIR theranostics with nanocarriers, molecularly precise self-assembly of NIR theranostics, and sense-of-logic NIR theranostic prodrug. Attention is given to contributions during the period 2014–2019 and focused on molecularly NIR fluorescent theranostic prodrug for bio-imaging and targeted therapy in vitro and in vivo. In addition, the sensing mechanisms and interaction modes of representative NIR theranostics prodrugs are also discussed.
Section snippets
OFF-ON pattern based NIR theranostics
In situ tracking of prodrugs after in vivo uptake, particularly in a non-invasive manner, is of critical importance. Notably, equipping with high-performance fluorophores as optical reporters have become an attractive strategy for monitoring the drug delivery and release process However, owing to poor photo-stability of NIR fluorescent reporters, there is still a lack of in vivo and in situ tracking of the drug release. As typical donor-π-acceptor (D-π-A) structured chromophores,
Dual-channel pattern based NIR theranostics
It is worth noting that most of currently NIR fluorescent prodrugs suffered from only one-channel turn-on emission. In this regard, the in vivo biodistribution of prodrugs before activation in a certain organ or tissue become blind. In 2016, Zhu et al. designed and synthesized a dual-channel NIR fluorescence activatable theranostic prodrug for real-time tracking where, when, and how (WWH) prodrugs are delivered and activated (Scheme 1b) [99]. The cyanine moiety and CPT are covalently bridged
Physically encapsulated NIR theranostics
The creation of nanotheranostics based on molecular prodrugs can promise such immense benefits for targeted therapies. Most of current drug delivery strategies mainly focus on physical entrapment, including polymers, liposomes and inorganic materials. With the help of these nanovesicles, drugs with prolonged blood circulation duration and enhanced permeability and retention (EPR effect) show more effective and specific cancer treatment than free drugs (Scheme 1c) [[101], [102], [103], [104]].
Molecularly precise self-assembly of NIR theranostics
Small molecule fluorescent prodrugs loaded in nanocarriers have passive tumor-targeting ability (EPR effect) as promising theranostics and perform the activatable release in tumors [107]. However, structural heterogeneity, inevitable leakage and non-uniform loading efficiency are insuperable barriers. To address these hurdles, the design of monodisperse nanomaterials with a single, reproducible entity that possesses both in vivo diagnostic and therapeutic competencies is in demand (Scheme 1d).
Sense-of-logic NIR theranostic prodrug
Current multi-stimulus-responsive probes are predominantly operated by “OR” logic gates in response to each stimulus. However, nonspecific activation in complex biological milieu always leads to “false positive” signals with difficulty in accurate recognition. For precisely controlling the drug release in vivo, Yan et al. presented a proof-of-concept study of a sequence activated AND logic dual-channel NIR fluorescent probe P(Cy-S-CPT) (Scheme 1e and Fig. 10), which functions as a programmable
Conclusions and perspectives
In this review, recent advances (2014–2019) made in the study NIR fluorescent theranostics prodrugs were overviewed. Particular attention was focused on how the utilization of NIR fluorescent probes for in vivo sense-and-release in the design of molecular theranostics. Despite tremendous advances in cancer therapy, the integration of multimodality diagnostic into a single-entity of molecular thernanostics remains great challenges for in vivo tracking tumor-specific chemotherapy. For instance,
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 21788102, 21421004, 21636002, 21622602 and 21908060), National Key Research and Development Program (No. 2017YFC0906902), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03), the Innovation Program of Shanghai Municipal Education Commission, Scientific Committee of Shanghai (No. 15XD1501400), and China Postdoctoral Science Foundation (No. 2019M651417).
Prof. Zhiqian Guo received his B.S. degree in Fine Chemicals from Zheng Zhou University in 2002. Then, he received his pH.D. degree of Applied Chemistry from East China University of Science & Technology (ECUST) in 2010 (Advisor: Professor Weihong Zhu). From 2011 to 2012, he worked with Prof. Dr. Juyoung Yoon (Ewha Womans University/Korea) on organic chemistry. He became a full professor at the School of Chemistry and Molecular Engineering at ECUST in 2017. He was a recipient of NSFC for
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Prof. Zhiqian Guo received his B.S. degree in Fine Chemicals from Zheng Zhou University in 2002. Then, he received his pH.D. degree of Applied Chemistry from East China University of Science & Technology (ECUST) in 2010 (Advisor: Professor Weihong Zhu). From 2011 to 2012, he worked with Prof. Dr. Juyoung Yoon (Ewha Womans University/Korea) on organic chemistry. He became a full professor at the School of Chemistry and Molecular Engineering at ECUST in 2017. He was a recipient of NSFC for Excellent Young Grants (2016), and Cheung Kong Young Scholar (Younger Project) (2017). His current research interests focus on functional chromophores, including fluorescent sensors, drug delivery system and molecular logic devices.