摘要
Etoposide,a DNA damage-inducing agent,is widely used for malignant tumors.However,insufficient solubility,poor bioavailability and adverse events limited the treatment outcomes and prognosis.To address this,we here developed a novel biosynthetic and unfolded protein nanocarrier to load and deliver Etoposide.Compared with the pristine agent,the loading efficiency of the nanoformulated drug increased four times and the half-life time increased to 17.6 h with controlled release of the Etoposide for 6 days.The half-maximal inhibitory concentration at 48 h was lower than that at 24 h,suggesting a long-acting anti-tumor property.Moreover,the anti-tumor performance in rat models was significantly enhanced by improving solubility and cellular internalization.Additionally,immunogenicity and adverse toxicologic effects such as kidney and liver toxicity were significantly weakened.Therefore,the assembly strategy enables etoposide with higher efficacy,bioavailability,and safety,and has great potential in the comprehensive treatment of malignant tumors.
基金
supported by the National Key R&D Program of China(Nos.2020YFA0712102,2018YFA0902600,2021YFF0701800,2020YFA0211100)
the National Natural Science Foundation of China(Nos.52222214,22020102003,22125701,21907088,51922077,51872205)
the Youth Innovation Promotion Association of CAS(No.2020228)
Natural Science Foundation of Jilin Province(No.20210101366JC)
the Foundation of National Facility for Translational Medicine(Shanghai)(No.TMSK-2020-012)
All animal experiments were conducted in compliance with the Animal Management Rules of the Ministry of Health of the People’s Republic of China and with the approval of the Institutional Animal Care and Use Committee of the Animal Experiment Center of Peking University(No.LA2019313).
