微泡辅助超声介导体内 IL-12 质粒递送在 B16F10 小鼠黑色素瘤模型中的治疗疗效：一项概念验证

In-vivo targeted delivery of immunostimulatory molecules for melanoma treatment is a promising strategy to overcome complexity, toxicity, and cost associated with current immunotherapies. Among these molecules, interleukine-12 (IL-12) is a potent immunostimulatory cytokine that plays a major role in antitumoral immune response.

However, systemic administration of IL-12 induces severe side effects, highlighting the need for efficient and safe in-vivo delivery modalities. Microbubble-assisted ultrasound (MB-assisted US) is an emerging non-invasive and targeted method for therapeutic molecule delivery.

This study aimed to evaluate its efficacy for intratumoral (i. t.) delivery of a plasmid encoding IL-12 (pIL-12) in a mouse melanoma model. In-vitro, delivery of 5 or 10 g of pIL-12 into melanoma cell suspensions using MB-assisted US increased IL-12 concentration to 1429 125 and 2352 125 pg/mL, respectively, whereas pIL-12 treatment alone did not elicit IL-12 secretion.

Similarly, acoustically mediated delivery of 10 or 50 g of pIL-12 into melanoma spheroids significantly increased IL-12 concentration - 131 7 and 250 60 pg/mL respectively - compared to pIL-12 alone (0 pg/mL for 10 g and 7. 5 7. 5 pg/mL for 50 g).

In-vivo, acoustically mediated pIL-12 delivery increased serum mIL-12 concentration by 5-fold compared with i. t. pIL-12 injection alone, promoting NK cell recruitment and activation within the tumor microenvironment. By day 15, this strategy reduced tumor volume by 2. 5-fold relative to i. t. pIL-12 alone and improved mouse health status.

These findings confirm that MB-assisted US is a relevant modality for in-vivo delivery of immunostimulatory molecules in melanoma therapy.