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A highly hemocompatible erythrocyte membrane-coated ultrasmall selenium nanosystem for simultaneous cancer radiosensitization and precise antiangiogenesis.

ABSTRACT: Radiotherapy is a vitally important strategy for clinical treatment of malignant cancers. Therefore, rational design and development of radiosensitizers that could enhance radiotherapeutic efficacy has attracted tremendous attention. Antiangiogenesis therapy could be a potentially effective strategy to regulate tumor growth and metastasis due to angiogenesis plays a pivotal role for tumor growth, invasion and metastasis to other organs. Herein, we have rationally designed a smart and effective nanosystem by combining ultrasmall selenium nanoparticles and bevacizumab (Avastin™, Av), for simultaneous radiotherapy and antiangiogenic therapy of cancer. The nanosystem was further coated with red blood cell (RBC) membranes to develop the final construct, RBCs@Se/Av. The RBC membrane coating effectively prolongs the blood circulation time and reduces the elimination of the nanosystem by autoimmune responses. As expected, RBCs@Se/Av, when irradiated with X-ray demonstrated potent anticancer and antiangiogenesis response in vitro and in vivo, as evidenced by strong inhibition of A375 tumor growth in nude mice, without causing any obvious histological damage to the non-target major organs. Taken together, this study demonstrates an effective strategy for design of smart Se-based nanosystem decorated with RBC membrane for simultaneous cancer radiosensitization and precise antiangiogenesis.

SUBMITTER: Liu T

PROVIDER: S-EPMC6234506 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A highly hemocompatible erythrocyte membrane-coated ultrasmall selenium nanosystem for simultaneous cancer radiosensitization and precise antiangiogenesis.

Liu Ting T Shi Changzheng C Duan Linqi L Zhang Zehang Z Luo Liangping L Goel Shreya S Cai Weibo W Chen Tianfeng T

Journal of materials chemistry. B 20180629 29

Radiotherapy is a vitally important strategy for clinical treatment of malignant cancers. Therefore, rational design and development of radiosensitizers that could enhance radiotherapeutic efficacy has attracted tremendous attention. Antiangiogenesis therapy could be a potentially effective strategy to regulate tumor growth and metastasis due to angiogenesis plays a pivotal role for tumor growth, invasion and metastasis to other organs. Herein, we have rationally designed a smart and effective n ...[more]

PMID: 30450208

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Project description:Two important features are required for promising radiosensitizers: one is selective tumor cell targeting to enhance the therapeutic outcome via lethal DNA damage and the other is rapid clearance to enable excellent biocompatibility for potential clinical application. Herein, ultrasmall gold nanoparticles (Au NPs) with diameter smaller than 5 nm were prepared and covered with a multifunctional peptide to endow them with selective tumor cell uptake capability. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing toxicity and rapid renal clearance in vivo. Methods: A responsive peptide (Tat-R-EK) consists of three build blocks were used: a cell and even nuclear penetrating block derived from human immunodeficiency virus-1 transactivator of transcription protein (Tat), an cathepsin B cleavable linker, and a zwitterionic antifouling block. Ultrasmall Au NPs were prepared and then covered by the peptide via the Au-S bonds between gold and thiol groups from cysteine. The morphology, colloidal stability and the responsiveness of obtained Au@Tat-R-EK NPs were studied using transmittance electron microscopy and dynamic laser scattering. The selective cancer cell uptake and accumulation of Au@Tat-R-EK NPs in cancer tissue were studied via ICP-MS in vitro and in vivo, respectively. The cytotoxicity of Au@Tat-R-EK NPs on HepG2 cancer cells was evaluated in terms of cell viability, DNA damage, intracellular reactive oxygen species generation, and apoptosis analysis. Finally, the biocompatibility and tumor destruction ability against orthotopic LM3 liver cancers were verified in vivo. Results: Multifunctional peptide modified ultrasmall Au NPs were successfully prepared. The Au NPs exhibited enough colloidal stability and cathepsin B-responsive surface change, leading to selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing cytotoxicity in vitro and therapeutic outcome on mouse liver cancer in vivo. The ultrasmall size enables rapid clearance of the Au NPs, guarantees the biocompatibility in vivo for potential clinical applications. Conclusion: Some obstacles faced by the Au NPs-based radiotherapy, such as short circulation half-life, non-specific distribution, slow clearance and low radio-sensitizing effect, were effective solved through rational design of the smart nanomedicine. This work provides new insight in designing tumor microenvironment-responsive nanomedicine in cancer radiotherapy.

Dataset Information

A highly hemocompatible erythrocyte membrane-coated ultrasmall selenium nanosystem for simultaneous cancer radiosensitization and precise antiangiogenesis.

Publications

A highly hemocompatible erythrocyte membrane-coated ultrasmall selenium nanosystem for simultaneous cancer radiosensitization and precise antiangiogenesis.

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