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用携带阿霉素和小干扰RNA的仿生纳米颗粒协同治疗骨肉瘤

Synergistic treatment of osteosarcoma with biomimetic nanoparticles transporting doxorubicin and siRNA.

作者信息

Zhao Jingtong, Mu Xupeng, Hou Xuejia, Zhang Xiaowen, Li Ping, Jiang Jinlan

机构信息

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

Rheumatology and Immunology Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Front Oncol. 2023 Jan 23;13:1111855. doi: 10.3389/fonc.2023.1111855. eCollection 2023.

DOI:10.3389/fonc.2023.1111855
PMID:36756155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9900173/
Abstract

INTRODUCTION

Osteosarcoma tumors are the most common malignant bone tumors in children and adolescents. Their treatment usually requires surgical removal of all detectable cancerous tissue and multidrug chemotherapy; however, the prognosis for patients with unresectable or recurrent osteosarcoma is unfavorable. To make chemotherapy safer and more effective for osteosarcoma patients, biomimetic nanoparticles (NPs) camouflaged by mesenchymal stem cell membranes (MSCMs) were synthesized to induce osteosarcoma cell apoptosis by co-delivering the anticancer drug doxorubicin hydrochloride(DOX) and a small interfering RNA (siRNA). Importantly, these NPs have high biocompatibility and tumor-homing ability. This study aimed to improve the efficacy of osteosarcoma therapy by using the synergistic combination of DOX and an siRNA targeting the apoptosis suppressor gene survivin.

METHODS

Biomimetic NPs (DOX/siSUR-PLGA@MSCM NPs) were synthesized by coloading DOX and survivin siRNA (siSUR) into poly (lactide-co-glycolide acid) (PLGA) a double-emulsion solvent evaporation method. The NPs were camouflaged by MSCMs to deliver both DOX and survivin-targeting siRNA and characterized and evaluated in terms of cellular uptake, release, and antitumor effects, and biosafety.

RESULTS

DOX/siSUR-PLGA@MSCM NPs had good tumor-homing ability due to the MSCMs modification. The drug-laden biomimetic NPs had good antitumor effects in homozygous MG63 tumor-bearing mice due to the synergistic effect of the drug combination.

CONCLUSION

DOX/siSUR-PLGA@MSCM NPs can show improved therapeutic effects in osteosarcoma patients due to the combination of a chemotherapeutic drug and gene therapy based on their good tumor targeting and biosafety.

摘要

引言

骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤。其治疗通常需要手术切除所有可检测到的癌组织并进行多药化疗；然而，不可切除或复发性骨肉瘤患者的预后不佳。为了使化疗对骨肉瘤患者更安全、更有效，合成了由间充质干细胞膜（MSCM）伪装的仿生纳米颗粒（NPs），通过共同递送抗癌药物盐酸多柔比星（DOX）和小干扰RNA（siRNA）来诱导骨肉瘤细胞凋亡。重要的是，这些纳米颗粒具有高生物相容性和肿瘤归巢能力。本研究旨在通过使用DOX和靶向凋亡抑制基因survivin的siRNA的协同组合来提高骨肉瘤治疗的疗效。

方法

通过将DOX和survivin siRNA（siSUR）共负载到聚（丙交酯-乙交酯）（PLGA）中，采用双乳液溶剂蒸发法合成仿生纳米颗粒（DOX/siSUR-PLGA@MSCM NPs）。纳米颗粒由MSCM伪装，以递送DOX和靶向survivin的siRNA，并在细胞摄取、释放、抗肿瘤作用和生物安全性方面进行表征和评估。

结果

由于MSCM修饰，DOX/siSUR-PLGA@MSCM NPs具有良好的肿瘤归巢能力。载药仿生纳米颗粒由于药物组合的协同作用，在纯合MG63荷瘤小鼠中具有良好的抗肿瘤作用。

结论

DOX/siSUR-PLGA@MSCM NPs由于具有良好的肿瘤靶向性和生物安全性，将化疗药物与基因治疗相结合，可在骨肉瘤患者中显示出更好的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/f337beebd2d1/fonc-13-1111855-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/d4f186b023cb/fonc-13-1111855-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/5cc30f43d96e/fonc-13-1111855-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/95ce39ff1802/fonc-13-1111855-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/432b478d5a18/fonc-13-1111855-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/f9f1947ce448/fonc-13-1111855-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/7241d8d0ab77/fonc-13-1111855-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/f337beebd2d1/fonc-13-1111855-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/d4f186b023cb/fonc-13-1111855-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/5cc30f43d96e/fonc-13-1111855-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/95ce39ff1802/fonc-13-1111855-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/432b478d5a18/fonc-13-1111855-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/f9f1947ce448/fonc-13-1111855-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/7241d8d0ab77/fonc-13-1111855-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/9900173/f337beebd2d1/fonc-13-1111855-g007.jpg

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