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中性粒细胞介导的多阶段纳米颗粒递呈用于促进肿瘤光热治疗。

Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy.

机构信息

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

出版信息

J Nanobiotechnology. 2020 Sep 29;18(1):138. doi: 10.1186/s12951-020-00682-7.

Abstract

BACKGROUND

Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer.

RESULTS

Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days).

CONCLUSIONS

Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.

摘要

背景

基于中性粒细胞的药物传递系统在靶向肿瘤方面具有优异的优势,因为中性粒细胞很容易被肿瘤微环境中的趋化因子募集。在此,我们开发了一种新型的多阶段基于中性粒细胞的纳米粒子递药系统,以促进肺癌的光热治疗(PTT)。

结果

金纳米棒(AuNR)成功地被牛血清白蛋白(AuNRB)修饰,然后与 RGD(AuNRBR)缀合,接着被中性粒细胞内化以获得基于中性粒细胞的递药系统(AuNRBR/N)。工程化的中性粒细胞由于炎症信号而有效地穿过上皮细胞迁移。它们在体外激光照射下对 Lewis 细胞表现出更好的毒性。此外,与无细胞载体的 AuNRBR 相比,AuNRBR/N 对肿瘤组织具有明显更高的靶向性,在 Lewis 荷瘤小鼠中得到了证实。AuNRBR/N 的增强的肿瘤归巢效率以及随后从中性粒细胞中释放的 AuNRBR 有利于进一步的深层组织扩散,并有助于抑制 PTT 中的肿瘤生长和提高存活率(超过 120 天)。

结论

总体结果表明,用于癌症 PTT 的基于细胞的纳米粒子递药系统的设计具有广阔的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/7523400/67b9b5b71d07/12951_2020_682_Fig1_HTML.jpg

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