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TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy.

ABSTRACT: Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. Methods: The Fe3+ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs). Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe3+/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T1-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation. Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.

SUBMITTER: Luo Y

PROVIDER: S-EPMC7295044 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy.

Luo Yuanli Y Qiao Bin B Zhang Ping P Yang Chao C Cao Jin J Yuan Xun X Ran Haitao H Wang Zhigang Z Hao Lan L Cao Yang Y Ren Jianli J Zhou Zhiyi Z

Theranostics 20200525 15

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. <b>Methods:</b> The Fe<sup>3+</sup> and tannic acid (TA) coordination were self-deposited on doxorubicin (D ...[more]

PMID: 32550917

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Project description:Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.

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TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy.

Publications

TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy.

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