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

The associated killing of hepatoma cells using multilayer drugloaded mats combined with fast neutron therapy

Yanxin Qi1,2,3, Shiwei Jing4, Shasha He2, Hejian Xiong2, Guohua Yang5, Yubin Huang2 (✉), and Ningyi Jin1,3 (✉)

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1 Medical College, Yanbian University, Yanji 133002, China
2 State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
3 Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Changchun 130122, China
4 Northeast Normal University, Changchun 130024, China
5 Changchun Medical College, Changchun 130031, China

Keywords: fast neutron therapy, dichloroacetate, control release, combination therapy, subcutaneous or orthotopic tumor model
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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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The associated killing of hepatoma cells using multilayer drugloaded mats combined with fast neutron therapy. Nano Res. https://doi.org/10.1007/s12274-020-3113-1

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