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Issue 22, 2018
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Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy

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Abstract

Structural heterogeneity and the lack of in vivo real-time tracking of drug release are the utmost barriers for nanocarrier-mediated prodrugs in targeted therapy. Herein, we describe the strategy of molecularly precise self-assembly of monodisperse nanotheranostics for BPn-DCM-S-CPT (n = 0, 5 and 20) with fixed drug loadings (36%, 23% and 16%) and constant release capacities, permitting in vivo real-time targeted therapy. We focus on regulating the hydrophilic fragment length to construct stable, well-defined nanostructured assemblies. Taking the bis-condensed dicyanomethylene-4H-pyran (DCM) derivative as the activatable near-infrared (NIR) fluorophore, it makes full use of two terminal conjunctions: the hydrophobic disulfide-bridged anticancer prodrug camptothecin (CPT) and the hydrophilic oligomer-bridged biotin segment serving as an active targeting unit. From the rational design, only BP20-DCM-S-CPT forms uniform and highly stable self-assemblies (ca. 80 nm, critical micelle concentration = 1.52 μM) with several advantages, such as structural homogeneity, fixed drug loading efficiency, real-time drug release tracking and synergistic targeting (passive, active and activatable ability). More importantly, in vitro and in vivo experiments verify that the surface-grafted biotins of nanoassemblies are directly exposed to receptors on cancer cells, thus markedly facilitating cellular internalization. Notably, through synergistic targeting, BP20-DCM-S-CPT displays excellent tumor-specific drug release performance in HeLa tumor-bearing nude mice, which has significantly enhanced in vivo antitumor activity and nearly eradicates the tumor (IRT = 99.7%) with few side effects. For the first time, the specific molecularly precise self-assembly of BP20-DCM-S-CPT within a single-molecular framework has successfully achieved a single reproducible entity for real-time reporting of drug release and cancer therapeutic efficacy in living animals, providing a new insight into amphiphilic nanotheranostics for clinical translation.

Graphical abstract: Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy

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Publication details

The article was received on 06 Mar 2018, accepted on 19 Apr 2018 and first published on 24 Apr 2018


Article type: Edge Article
DOI: 10.1039/C8SC01069B
Citation: Chem. Sci., 2018,9, 4959-4969
  • Open access: Creative Commons BY license
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    Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy

    C. Yan, Z. Guo, Y. Shen, Y. Chen, H. Tian and W. Zhu, Chem. Sci., 2018, 9, 4959
    DOI: 10.1039/C8SC01069B

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