MiRNA-based gene therapy as a novel targeted
therapy has yielded promising results in experimental
cancer treatment, however, the inefficient delivery of
miRNA to target tissues has limited its application in vivo. Here a unique dual-membrane-camouflaged miRNA21
antagomir delivery nanoplatform (M@NPs/miR21) with immune escape and homologous targeting properties was constructed by
cancer cell membrane and macrophage membrane. Different from the single-cell membrane camouflage strategy, the dual-membrane camouflage miRNA21
antagomir delivery nanoplatform based on modification of CD47
protein with immune escape signal and
galectin-3 protein with
tumor cell aggregation enables efficient, safe and targeted
therapy for
colon cancer and lung
metastases. Camouflaged with the dual-cell membrane, the "Trojan horse" like "pseudo-
tumor cell" and/or "pseudo-macrophage" (M@NPs/miR21) carried the target gene miR21
antagomir to the
tumor site and showed significant anti-
tumor properties at the periphery and the core of subcutaneous
tumor tissues. In addition, M@NPs/miR21 was more likely to penetrate dense
tumor tissues and function within the
tumor mass than NPs/miR21 without membrane coating. M@NPs/miR21 can deliver miR21
antagomir into MC38
cancer cells and
tumor tissues, promote
tumor apoptosis, and regulate the expression of Bcl2 and Ki67. Moreover, the M@NPs/miR21 gene delivery system not only can effectively inhibit the progression of subcutaneous
tumors and lung
metastases, but also showed minimal toxicity and good biosafety, making this delivery system particularly attractive for future translational research.