Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery. The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146–199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles. This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

In this study, we synthesized thermo-responsive and photo-cleavable amphiphilic block copolymers containing photodegradable linkers as junction points between hydrophilic and hydrophobic chains. We synthesized PNiPAAm-ONB-PXCL block copolymers by using a combination of ring-opening polymerization and nucleophilic substitution reactions using 5-hydroxy-2-nitrobenzyl alcohol as a difunctional photo-responsive initiator. These PNiPAAm-ONB-PXCL copolymers consisting of soft domains of amorphous PNiPAAm and PXCL exhibited amorphous T_g. The polymer micelles exhibited dual responsiveness to heat and light. The lower critical solution temperature of PNiPAAm₂₀-ONB-PMCL₄₉ was 39.3 °C, which is approximately the temperature of tumor tissue. When we exposed the polymer solutions to ultraviolet (UV) irradiation, we observed major changes in the structure and morphology of the particles. Fluorescence emission measurements indicated the release of Nile red (NR), a hydrophobic dye, encapsulated by the PNiPAAm-ONB-PXCL micelles, in response to irradiation because of disruption of the micelles. Release of indomethacin (IMC) was rapid under UV irradiation at 42 °C and approximately 90% of the encapsulate IMC was released in a sustained manner during the first 7 h. The nanoparticles were associated with nonsignificant toxicity at concentrations <100 μg mL⁻¹. Doxorubicin (DOX)-loaded micelles facilitated the uptake of DOX by HeLa cells within 30 min of treatment, and were predominantly retained in the cytoplasm. The DOX-loaded micelles were associated with low cytotoxicity against HeLa cells.

Triple stimuli-responsive polymers PNiPAAm-S-S-PXCL containing a disulfide (–S–S–) bond as a junction point between hydrophilic and hydrophobic chains were synthesized through ring-opening polymerization (ROP) and nucleophilic substitution. When the polymer solutions were treated with reducing agents and exposed to ultrasound, significant hydrolysis of the amide bonds was observed. The morphology of the particles and the changes in the fluorescence intensity of Nile red revealed that the copolymers underwent micellization or dissociation transitions in water in response to temperature variation, reducing agent treatment, and ultrasound. The release rate could be greatly increased and adjusted remotely under high intensity focused ultrasound in the presence of dithiothreitol. The nanoparticles exhibited slight toxicity against HeLa cells in the concentration range 10–1000 μg mL⁻¹. The DOX-loaded PNiPAAm₂₁-S-S-PMCL₂₅ micelles effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration of 2.33 μg mL⁻¹. The multiple stimuli-responsive polymeric nanoparticles show promising potential as new nanocarriers for controlled release.

Amphiphilic photo and redox dual-stimuli-cleavable β-cyclodextrin-ferrocene supramolecules were synthesized through noncovalent interactions of ferrocene (Fc) and β-cyclodextrin (β-CD) born by 5-hydroxy-2-nitrobenzyl alcohol (ONB), a photodegradable linker between the β-CD and poly(4-substituted-ɛ-caprolactone) (PXCL _n ) chain. The terminal host–guest MPEG-Fc/β-CD-ONB-PXCL _n complex can formed micelles in the aqueous phase. The critical micelle concentration ranged from 3.16 to 11.50 mg L⁻¹. The drug-loading content and drug entrapment efficiency of the complex were lower than those of the parent β-CD. When exposed to ultraviolet irradiation and hydrogen peroxide, complex micelles could dissociate and efficiently release the loaded drug. Nanoparticles exhibited almost no toxicity at concentrations up to 1000 μg mL⁻¹. The uptake of doxorubicin-incorporated micelles by HeLa cells was faster than that of free doxorubicin within the first 5 min. DOX-loaded MPEG₄₅-Fc/β-CD-ONB-PMCL₂₃ micelles effectively inhibited the proliferation of HeLa cells with a half maximal inhibitory concentration (IC₅₀) of 3.8 µg mL⁻¹.