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. 2014 Aug 10;21(5):730–754. doi: 10.1089/ars.2013.5754

Table 7.

Examples of Thioether-Based Oxidation-Responsive Systems

Polymer structure Formulation Oxidant Response to oxidation Evidence of degradation Ref.
EG16-PS50-EG16 Triblock macro-amphiphiles unilamellar vesicles; membrane ∼8 nm thick 0.03%–10% H2O2 (∼9 mM-3 M) HLB alteration and vesicle disruption due to the oxidation of the hydrophobic PPS blocks into hydrophilic polypropylene sulfoxides and sulfones OD, clear: 10% H2O2 (10 h), 0.03% (300 h) (139)
        TEM, vesicle number, shape change: 10% H2O2 (few min), 0.03% H2O2 (150 min)  
        NMR, appearance of sulfoxides and sulfones  
Poly(PS74-b-DMA310) 100 nm micelles 1.1 mM-1.1 M H2O2, 1–100 μM ONOO, or 1–100 mM SIN-1 PPS oxidation causes micelles disassembly into unimeric polymers and cargo release NMR, sulfone formation in H2O2 (76)
        DLS+TEM, disruption, 1.1 M H2O2  
        NR or DiO release correlating to H2O2, ONOO, or SIN-1 conc.  
Disulfide cross-linked PPS 25–225 nm Pluronic F127-stabilized PPS NP 5%–10% H2O2 (∼1.5–3 M) Swelling and solubilization after conversion to hydrophilic polypropylene sulfoxides and sulfones OD, loss of turbidity: 5% H2O2 (30 h), 10% H2O2 (95 h) (149)
PPS 150 nm Pluronic F127-stabilized PPS NP 25–200 ppm PPS oxidation causes swelling and cargo release OD, transmittance incr. (3)
    NaOCl   Reichardt's dye release, 98%, 5 min (2000 ppm NaOCl)  
    CPO and hMPO+200 mM NaCl, 500 μM H2O2   NR: transmittance incr. 17%, fluor. decr. 70% (CPO); transm. incr. 10%, fluor. decr. 80% (hMPO)  
PPADT 600 nm NP KO2 (unknown level) Cleavage of thioketal linkages on oxidation GPC, PPADT degradation in 8 h (high or low pH, no change) (196)
Poly(thio-ether ketal) 200 nm NP 100 mM H2O2 Dual response:
thioether oxidation into sulfoxides produces more swollen and hydrophilic particles, enabling ketal hydrolysis and payload release
DLS, NP degradation, pH 5/100 mM H2O2, 15 h (125)
    pH: 5, 6.5, and 7.4   NMR, complete hydrolysis in 2 d  
        NR quenching: >80% in 25 h, 100 mM H2O2 (pH 5 or pH 7); <30% in abs.  
        OVA release: ∼100% in 100 mM H2O2 (pH 6.5); <20% without H2O2  

DLS, dynamic light scattering; EG, ethylene glycol; GPC, gel permeation chromatography; HLB, hydrophilic to lipophilic balance; hMPO, human myeloperoxidase; Mn, number average molecular weight; OD, optical density; PPS, poly(propylene sulfide); PS, propylene sulfide; PGSE, pulse gradient spin echo; PPADT, poly-(1,4-phenyleneacetone dimethylene thioketal); poly(PS74-b-DMA310), a diblock polymer of propylene sulfide (PS) and N,N-dimethylacrylamide; DiO, (3,3′-dioctadecyloxacarbocyanine perchlorate); CPO, chloroperoxidase; OVA, ovalbumin Alexa Fluor 594; NMR, nuclear magnetic resonance.