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. 2022 May 18;8(20):eabn7382. doi: 10.1126/sciadv.abn7382

Fig. 1. Schematic illustration of hierarchical self-uncloaking RNCOs-D assembly/disassembly for synergistic gene therapy/chemotherapy after specific cellular uptake.

Fig. 1.

(A) Sequence design of circular template and formation of RNCOs-D composed of RCT-assembled RNSs and acid-degradable NCs. (B) Intracellular self-uncloaking hierarchy of RNCOs-D for cancer therapy. (I) Outer decomposition of NCs induced by acidic endo/lysosomal microenvironment with concomitant Cas13a/crRNA release as the first self-uncloaking. (II) Inner dissociation of RNSs through multisite trans-cleavage initiated by monosite cis-recognition and cleavage of EGFRvIII mRNA to release DOX as the second self-uncloaking. (III) Synergistic gene therapy/chemotherapy.