MicroRNA-Guided Selective Release of Loads from Micro-/Nanocarriers Using Auxiliary Constitutional Dynamic Networks

Two different drug micro-carriers consisting of doxorubicin-dextran (DOX-D)- and camptothecin-modified carboxymethyl cellulose (CPT-CMC)-loaded nucleic acid-stabilized microcapsules, MC-1 and MC-2, or two different nanocarriers consisting of nucleic-acid-locked doxorubicin (DOX)- and camptothecin (CPT)-loaded metal-organic framework nanoparticles, NMOF-1 and NMOF-2, are coupled to auxiliary constitutional dynamic networks, CDNs, for the triggered release of the drugs. CDN S composed of four constituents AA '', AB', BA', and BB', and two hairpin structures, H-1 and H-2, leads to the CDN S-guided unlocking of the MC-1/MC-2 carriers and the release of DOX-D and CPT-CMC or of the NMPF-1 and NMOF-2 carriers that release DOX and CPT, respectively. The unlocking processes are activated by the cleavage of H-1 and H(2 )by BB' and BA', respectively, to yield fragmented strands that unlock the gating units of the microcapsules/NMOFs carriers. In the presence of miRNA-155 or miRNA-124, dictated orthogonal reconfiguration of CDN S into CDN X or Y proceeds. The miRNA-155 stimulates the reconfiguration of CDN S to CDN X, where AA' and BB' are upregulated, and AB' and BA' are downregulated, leading to the enhanced release of DOX-D or DOX from the microcapsule/NMOFs carriers, and to the concomitant inhibition of the release of CPT-CMC or CPT from the respective carriers. Similarly, the miRNA-124-triggered reconfiguration of CDN S to CDN Y results in the BA'-guided cleavage of H-2 and the preferred release of CPT-CMC or CPT from the respective carriers. The miRNA-triggered CDN-driven unlocking of the carriers stimulates the amplified and selective release of the drugs from the microcapsules/NMOFs carriers.