Optimization of microbubble-based DNA vaccination with low-frequency ultrasound for enhanced cancer immunotherapy.

Autor: Zhang N; Department of Radiology, Stanford University, Palo Alto, CA, USA., Foiret J; Department of Radiology, Stanford University, Palo Alto, CA, USA., Kheirolomoom A; Department of Radiology, Stanford University, Palo Alto, CA, USA., Liu P; Department of Radiology, Stanford University, Palo Alto, CA, USA., Feng Y; Department of Radiology, Stanford University, Palo Alto, CA, USA., Tumbale S; Department of Radiology, Stanford University, Palo Alto, CA, USA., Raie M; Department of Radiology, Stanford University, Palo Alto, CA, USA., Wu B; Department of Radiology, Stanford University, Palo Alto, CA, USA., Wang J; Department of Radiology, Stanford University, Palo Alto, CA, USA., Fite BZ; Department of Radiology, Stanford University, Palo Alto, CA, USA., Dai Z; Department of Engineering, Peking University, Beijing, China., Ferrara KW; Department of Radiology, Stanford University, Palo Alto, CA, USA.
Jazyk: angličtina
Zdroj: Advanced therapeutics [Adv Ther (Weinh)] 2021 Sep; Vol. 4 (9). Date of Electronic Publication: 2021 Jun 04.
DOI: 10.1002/adtp.202100033
Abstrakt: Immunotherapy is an important cancer treatment strategy; nevertheless, the lack of robust immune cell infiltration in the tumor microenvironment remains a factor in limiting patient response rates. In vivo gene delivery protocols can amplify immune responses and sensitize tumors to immunotherapies, yet non-viral transfection methods often sacrifice transduction efficiency for improved safety tolerance. To improve transduction efficiency, we optimized a strategy employing low ultrasound transmission frequency-induced bubble oscillation to introduce plasmids into tumor cells. Differential centrifugation isolated size-specific microbubbles. The diameter of the small microbubble population was 1.27 ± 0.89 μm and that of larger population was 4.23 ± 2.27 μm. Upon in vitro insonation with the larger microbubble population, 29.7% of cancer cells were transfected with DNA plasmids, higher than that with smaller microbubbles (18.9%, P <0.05) or positive control treatments with a commercial transfection reagent (12%, P < 0.01). After 48 h, gene expression increased more than two-fold in tumors treated with large, as compared with small, microbubbles. Furthermore, the immune response, including tumor infiltration of CD8 + T cells and F4/80 + macrophages, was enhanced. We believe that this safe and efficacious method can improve preclinical procedures and outcomes for DNA vaccines in cancer immunotherapy in the future.
Competing Interests: Conflict of Interest The authors declare no conflict of interest.
Databáze: MEDLINE
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