Dual Stimuli‐Responsive Polymeric Micelles Exhibiting “AND” Logic Gate for Controlled Release of Adriamycin

Abstract

A new controlled release polymer micelle was designed and synthesized based on the concept of the "AND" logic with two orthogonal molecular triggers, namely pH and reduction, for intracellular drug delivery. Specifically, a hydrazine functionalized PEO-b-PMAA block copolymer was used to attach adriamycin (ADR) through the formation of hydrazone, then the as-prepared ADR-conjugated block copolymer micelles could be crosslinked by dithiodiethanoic acid. ADR was found to release most efficiently under both the low pH and the reductive conditions. This smart device is therefore equipped with two triggers with the "AND" logic for the releasing action, which is suitable for more complicated physiological conditions because the "ON" state is only realized under the simultaneous presence of the dual signal stimuli.

Multi-stimuli responsive macromolecules and their assemblies

“…This was described as an “AND” logic gate, 43 since drug can be only released when both of pH and redox stimuli are present. In this study, a drug molecule, adriamycin (ADR) was first attached to a hydrazine functionalized poly(ethylene oxide) -b- poly(methacrylic acid) (PEO -b- PMAA) block copolymer (Figure 3) through the formation of hydrazone.…”

Challenges in design of translational nanocarriers

“…The resulting micelles formed from PEG-block-poly(L-amino acid) (PEG-b-PLAA)-conjugated drugs eliminated any burst release [29]. Using labile linkers responsive to the tumor's extracellular or intracellular stimuli results in drug release triggered in a tumor extracellular environment [30,31]. Our group demonstrated directly using drugs as the hydrophobic parts to make self-assembling amphiphilic prodrugs for fabricating burst-free carriers [32].…”

Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

“…1D). Wei et al constructed reduction and pH dual-sensitive DOX-conjugated CCL micelles from PEG-bpoly(methacrylic acid-g-hydrazone-DOX) diblock copolymer containing pendant hydrazide groups (PEG-b-P(MA-g-Hyd-DOX)) using dithiodiethanoic acid as a cross-linker (79). The resulting CCL micelles exhibited the fastest DOX release in response to both stimuli (pH 4.0 and 15 mM DTT).…”