Inducing a Proinflammatory Response with Bioengineered Yeast Vacuoles with TLR2-Binding Peptides (VacT2BP) as a Drug Carrier for Daunorubicin Delivery.

Abstract

Immune adjuvants have roles in immune activation for cancer therapy, and adjuvants derived from microbes have been applied. In this study, we propose the use of bioengineered vacuoles, derived from recombinant yeast with acute myeloid leukemia (AML) specificity and having a TLR-2-binding peptide (VacT2BP) on their surface, to induce a proinflammatory response as a dual-function nanomaterial for daunorubicin (DNR) delivery. Our results demonstrate that nanosized, isolated VacT2BP induced HL-60 cell-specific DNR delivery and apoptosis. Furthermore, we observed the selective release of high-mobility group box 1 from apoptotic HL-60 cells by DNR@VacT2BP. We concluded that DNR@VacT2BP exhibited target selectivity, and the indiscriminate occurrence of damage-associated molecular patterns (DAMPs) was inhibited by the VacT2BP carrier. The therapeutic efficacy of DNR@VacT2BP was confirmed in AML xenograft mice, with about 82% tumor growth inhibition. Following drug delivery, apoptotic cells and DAMPs with residual VacT2BP (apopDNR@VacT2BP) upregulated the proinflammatory immune response of macrophages. In addition, apopDNR@VacT2BP enhanced phagocytosis activity. Macrophages stimulated by apopDNR@VacT2BP suppressed cancer proliferation by about 40%. In summary, our results suggest that dual-functional vacuoles with a target-specific peptide can be a potential strategy for selective drug delivery and construction of an immune environment to fight cancer, thereby improving prognosis.