2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03I.18 Optimizing Delivery of Anti-Cancer Therapeutics in Lung Adenocarcinoma Using Ultrasound-Induced Cavitation of Microbubbles

P3.03I.18 Optimizing Delivery of Anti-Cancer Therapeutics in Lung Adenocarcinoma Using Ultrasound-Induced Cavitation of Microbubbles

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The study by Sanwal et al. explores improving the delivery of anti-cancer therapeutics for non-small cell lung cancer (NSCLC), specifically lung adenocarcinoma, by leveraging ultrasound-induced cavitation of microbubbles (USMB). The primary challenge addressed is the suboptimal delivery and selectivity of anti-cancer drugs, which often result in systemic toxicity when administered intravenously.<br /><br />USMB has been proposed as a promising method to enhance drug delivery selectively to tumor cells while minimizing systemic effects. Microbubbles used in conjunction with ultrasound can carry therapeutic agents like doxorubicin (Doxo) and siRNA. Upon exposure to ultrasound, these microbubbles cavitate, thereby enhancing drug uptake through mechanisms such as membrane pore formation and endocytosis.<br /><br />The study specifically investigates the potential of USMB to improve the efficacy of combination therapies that pair chemotherapeutics with anti-CD47 treatments. CD47, often upregulated in NSCLC, enables immune evasion by transmitting a "don't eat me" signal, thus blocking CD47 can potentially increase cancer cell phagocytosis.<br /><br />The results confirmed that USMB could improve the uptake of molecular cargo in NSCLC cells in vitro and in vivo, as illustrated by enhanced siRNA and Doxo uptake in cancer cells, and increased phagocytosis following CD47 knockdown. The study's objective is to develop a USMB-based therapeutic delivery system, test its efficacy in NSCLC models, and minimize the systemic toxicity of cancer treatments.<br /><br />Future work includes validating that Doxo increases 'eat me' signals in NSCLC and identifying optimal USMB conditions for targeted drug delivery in mice, with the goal of evaluating the combined strategy's effectiveness in tumor regression while ensuring specificity for tumor over non-tumor tissues.

Asset Subtitle

Ryunosuke Hoshi

Meta Tag

Speaker Ryunosuke Hoshi

Topic Tumor Biology – Translational Biology

Keywords

non-small cell lung cancer

NSCLC

ultrasound-induced cavitation

microbubbles

drug delivery

systemic toxicity

CD47

phagocytosis

siRNA

doxorubicin