biostudies-literatureWan LNational Natural Science Foundation of ChinaChongqing Natural Science Foundation102923https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933863biostudies-literatureUnknown37Oncolytic peptides offer a novel anticancer paradigm by inducing membrane lysis-mediated cancer cell death and subsequent anticancer immunity to overcome tumor heterogeneity and treatment resistance. Despite its promising profiles, the clinical application of oncolytic peptides (such as LTX-315) is hampered by ticklish reasons like rapid plasma clearance, suboptimal biodistribution, and potential toxicity toward normal tissues. Herein, we innovatively engineered an ultrasound-propelled cancer cell membranes-hybridized lipid microbubbles to load oncolytic peptide LTX-315 (LCMBs) for precise and controlled oncolytic therapy. The LCMBs enabled the targeted delivery and stimuli-responsive release of LTX-315 in the tumor site under low-intensity focused ultrasound (US). The high accumulation ofMaterials today. BioUltrasound-propelled oncolytic biomimetic microbubbles as <i>in situ</i> vaccines reprogram tumor immunosuppressive microenvironment.PMC12933863CSTB2025NSCQ-GPX11508257225682404524CSTB2024NSCQ-KJFZMSX0005Fu RJiao MYu LWu NChen JWan LTang CLi PLi RLi XHuang ZHu JTang RXia CLiang PfalseUltrasound-propelled oncolytic biomimetic microbubbles as <i>in situ</i> vaccines reprogram tumor immunosuppressive microenvironment.Oncolytic peptides offer a novel anticancer paradigm by inducing membrane lysis-mediated cancer cell death and subsequent anticancer immunity to overcome tumor heterogeneity and treatment resistance. Despite its promising profiles, the clinical application of oncolytic peptides (such as LTX-315) is hampered by ticklish reasons like rapid plasma clearance, suboptimal biodistribution, and potential toxicity toward normal tissues. Herein, we innovatively engineered an ultrasound-propelled cancer cell membranes-hybridized lipid microbubbles to load oncolytic peptide LTX-315 (LCMBs) for precise and controlled oncolytic therapy. The LCMBs enabled the targeted delivery and stimuli-responsive release of LTX-315 in the tumor site under low-intensity focused ultrasound (US). The high accumulation of2026-01-01T00:00:00Z2026 Apr2026-07-16T22:11:54.047Z2026-07-14T03:04:09.414ZS-EPMC129338634175652710.1016/j.mtbio.2026.102923