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The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy

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Abstract

Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice; however, to improve anticancer efficacy, combination chemotherapy still remains challenge. Dichloroacetate (DCA) could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism. Radiation therapy with fast neutrons (FNT) has high relative biolgical effectiveness compared to other radiotherapeutics. Herein, we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives. We first synthesized a biodegradable polylysine to condense DCA with negative charge, or to conjugate DCA by condensing synthesis, to obtain Ion-DCA and Co-DCA, respectively. DCA, Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats. Upon adhesion on the surface of subcutaneous and orthotopic liver tumors, the multilayer drug-loaded mats realized a controllable release of DCA, which reversed the Warburg effect and inhibited cancer cell proliferation. Meantime, irradiation of fast neutrons could seriously damage DNA structure. Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro, and the tumor inhibition in vivo. This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 51273194, 21975246 and 51903233).

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Authors and Affiliations

  1. Medical College, Yanbian University, Yanji, 133002, China

    Yanxin Qi & Ningyi Jin

  2. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Yanxin Qi, Shasha He, Hejian Xiong & Yubin Huang

  3. Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Changchun, 130122, China

    Yanxin Qi & Ningyi Jin

  4. Northeast Normal University, Changchun, 130024, China

    Shiwei Jing

  5. Changchun Medical College, Changchun, 130031, China

    Guohua Yang

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  1. Yanxin Qi
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Correspondence to Yubin Huang or Ningyi Jin.

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Qi, Y., Jing, S., He, S. et al. The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy. Nano Res. 14, 778–787 (2021). https://doi.org/10.1007/s12274-020-3113-1

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  • DOI: https://doi.org/10.1007/s12274-020-3113-1

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