Degradable Spirocyclic Polyacetal-Based Core-Amphiphilic Assemblies for Encapsulation and Release of Hydrophobic Cargo

Abstract

Polymeric nanomaterials that degrade in acidic environments have gained considerable attention in nanomedicine for intracellular drug delivery and cancer therapy. Among various acid-degradable linkages, spirocyclic acetals have rarely been used to fabricate such vehicles. In addition to acid sensitivity, they benefit from conformational rigidity that is otherwise not attainable by their non-spirocyclic analogs. Herein, amphiphilic spirocyclic polyacetals are synthesized by Cu-catalyzed alkyne–azide “click” polymerization. Unlike conventional block copolymers, which often form core–shell structures, these polymers self-assemble to form core amphiphilic assemblies capable of encapsulating Nile red as a hydrophobic model drug. In vitro experiments show that while release from these materials can occur at neutral pH with preservation of their integrity, acidic pH accelerates efficient cargo release and leads to the complete degradation of assemblies. Moreover, cellular assays reveal that these materials are fully cytocompatible, interact with the plasma membrane, and can be internalized by cells, rendering them as potential candidates for cancer therapy and/or drug delivery.

A New Biodegradable Linear mPEG‐b‐poly(Schiff Base‐Acetal) Copolymer Carrier Co‐Delivery Cinnamaldehyde and Gemcitabine for Combined Anticancer Therapy

“…It manifests that the polymer P1 micelle containing acetal and Schiff base moieties has pH‐responsiveness. The typical acetal proton peak (peak 8, 5.17 ppm) disappeared and aldehyde proton peak of cinnamaldehyde appeared were observed in the 1 H NMR spectroscopy of polymer P2 treated with acid PBS solution for 12 h (Figure S7B), which proved that the acetal moieties has been hydrolyzed and P2 micelles has pH‐responsiveness [17b,27] . The typical Schiff base proton peak (peak 6, 8.34 ppm) disappeared after incubated in acid PBS (5.0) solution for 12 h (Figure S8B), which manifested that the Schiff base structure of P3 has been degradation and P3 micelles has pH‐responsiveness.…”

Short-Loop Chemical Recycling via Telechelic Polymers for Biobased Polyesters with Spiroacetal Units

“…Furthermore, spirocyclic acetal structures are sensitive to acidic conditions, which can be utilized to design polymers with degradability or chemical recyclability. For instance, a spiroacetal epoxy monomer has been used to produce cellulose nanofiber composites with chemical recyclability. , Polymers with acetal structures have also been used as drug delivery systems with controlled release. , Biobased polyurethanes and polyesters with acetal units have also been conveniently degraded under acidic conditions, which can facilitate biodegradation or chemical recycling. ,, …”

“…16,17 Polymers with acetal structures have also been used as drug delivery systems with controlled release. 18,19 Biobased polyurethanes and polyesters with acetal units have also been conveniently degraded under acidic conditions, which can facilitate biodegradation or chemical recycling. 11,20,21 In most reported chemical recycling processes, polymers were completely broken into small compounds and monomers that can be further used for polymerizations.…”

Hyaluronic Acid-Based Nanocapsules as Efficient Delivery Systems of Garlic Oil Active Components with Anticancer Activity

“…Most studies focused on the molecular effects of these compounds report dissolving DADS [13,14] and DATS [15] in dimethyl sulfoxide (DMSO). However, during the last few decades, there have been an increasing number of works considering the delivery of hydrophobic actives using drug-delivery systems (DDSs) based on, e.g., polymers, including e.g., polysaccharides [16][17][18][19][20], liposomes [21], bilosomes [22]. In particular, the nanoscale systems are of high interest for the encapsulation of hydrophobic pharmaceuticals and nutraceuticals [23][24][25].…”