Near-infrared (NIR) light-triggered drug release systems are promising for drug delivery applications in view of the advantages of NIR light, which include high tissue penetration and low damage. In this report, we developed nanogels (NGs) by supramolecular self-assembly from adamantine (AD)-conjugated copolymer, poly[poly(ethylene glycol)monomethyl ether metharcylate]-co-poly(N-(2-hydroxypropyl)methacrylamide)-co-poly(N-adamantan-1-yl-2-methacrylamide) (PPEGMA-co-PHPMA-co-PADMA), and β-cyclodextrin (β-CD)-functionalized poly(amidoamine) (PAMAM) dendrimer based on the host–guest interaction of the AD and β-CD moieties, and they were used to encapsulate indocyanine green (ICG) and doxorubicin (DOX) for combined photothermal-chemotherapy. NGs simultaneously loading ICG and DOX (DINGs) showed significant photothermal effects and stimuli-triggered drug release under NIR laser irradiation by the photothermal-induced relaxation or dissociation of the NGs. In vitro cytotoxicity evaluation of DINGs under NIR irradiation demonstrated the synergistic effects of hyperthermia, photothermal-triggered drug release, and chemotherapy. In vivo investigation revealed their high accumulation in tumor tissue and significant tumor growth suppression under NIR irradiation. These NIR light-triggered drug release NGs represent efficient and promising anticancer drug vectors for the combined photothermal-chemotherapy of cancer to maximize therapeutic efficacy and minimize side effects.

The polymeric nanogels were constructed via host–guest interactions for dual pH-triggered multistage drug delivery, which showed tumor acidity-triggered nanogel reorganization into smaller nanoparticles for deep tissue penetration, high-efficiency cellular uptake, and intracellular endo-lysosomal pH-responsive drug release.

Biocompatible stimuli-responsive unimolecular polymeric micelles have attracted much interest due to their unique structures and potential applications in biomedical fields such as drug delivery and tissue engineering. Here, we report the preparation of dendritic unimolecular polymeric micelles with temperature sensitive shells via reversible addition–fragmentation transfer (RAFT) technique. A multi-arm star amphiphilic copolymer (H40-PDEA) with a hydrophobic hyperbranched polyester (Boltorn H40) as the core and the grafted poly(N,N-diethylacrylamide) (PDEA) as the shell was prepared using H40 based macroRAFT agent. And a dendritic unimolecular polymer (H40-PDEA–PDMA) with a double hydrophilic block copolymer (DHBC) [PDEA-b-poly(2-(dimethylamino)ethyl methacrylate) (PDEA-b-PDMA)] as the dual thermoresponsive shells was synthesized by H40-PDEA based macroRAFT agent. Both H40-PDEA and H40-PDEA–PDMA have a reversible phase transition behavior in aqueous solution. In particular, the unimolecular polymeric micelles H40-PDEA–PDMA with double thermoresponsive shells exhibit a two-stage phase transition behavior. Laser light scattering (LLS), UV–vis transmittance, excimer fluorescence measurements, and micro-differential scanning calorimetry (micro-DSC) were used in combination to probe the conformational changes of chains located at the inner layer and outer corona during the phase transition process.Graphical abstractThe dual stimuli-responsive umimolecular polymeric micelles (H40-PDEA–PDMA) with biocompatible coronas have two-stage reversible phase transition behavior during a heating-and-cooling cycle.Research highlights► The dual stimuli-responsive umimolecular polymeric micelles with biocompatible coronas. ► The unimolecular micelles present a reversible two-stage process in thermosensityive particle size change during a heating-and-cooling cycle. ► The architecture of core–shell–corona for polymeric micelles has a great potential for a variety of applications ranging from drug delivery, separation, to gene delivery.

This paper describes the reversible phase transition behavior of a thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) shell at the surface of a hydrophilic core. Reversible addition-fragmentation transfer (RAFT) polymerization of N-isopropylacrylamide was conducted using a hydrophilic hyperbranched poly(glycidol) (HPG)-based macroRAFT agent. At lower temperatures (<30 °C), the resultant multiarm star block copolymer (HPG–PNIPAM) exists as unimolecular micelles, with hydrophilic HPG as the core and a densely grafted PNIPAM brush as the shell. In laser light scattering (LLS) studies, the concentration used for HPG–PNIPAM is 5 × 10−6 g ml−1, to avoid any possible aggregation between dendritic unimolecular micelles above the lower critical solution temperature (~32 °C) of PNIPAM. What we observe for the phase transition of HPG–PNIPAM involves only unimolecular process. A combination of dynamic and static LLS studies of HPG–PNIPAM in aqueous solution reveals a reversible phase transition on heating and cooling.

The dendritic unimolecular polymeric micelles with a hydrophobic dendritic polyester (Boltorn H40) as the core and the grafted biocompatible poly(N, N-diethylacrylamide)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDEAAM-b-PDMAEMA) as the shell were synthesized by successive reversible addition–fragmentation transfer (RAFT) polymerization of N, N-diethylacrylamide (DEAAM) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomers. Laser light scattering studies indicated that the resulting unimolecular polymeric micelles H40–PDEAAM–PDMAEMA with double stimuli-responsive shells exhibited a reversible two-stage phase transition behavior. The effect of varying the block length of PDMAEMA on the thermosensitivity of unimolecular polymeric micelles was studied. With an increase in the outer corona length of PDMAEMA, the temperature range of phase transition for the inner shell PDEAAM would become broad. As pH decreased to 2, the high hydrophilic PDMAEMA blocks with high protonation were independent of temperature, and the size of unimolecular polymeric micelles increased due to the extended-chain conformation of outer layer. The internal core cavities of the unimolecular polymeric micelles exhibited a great potential of loading guest molecules according to the analysis of pyrene probe fluorescence spectra.

The polymeric nanogels were constructed via host–guest interactions for dual pH-triggered multistage drug delivery, which showed tumor acidity-triggered nanogel reorganization into smaller nanoparticles for deep tissue penetration, high-efficiency cellular uptake, and intracellular endo-lysosomal pH-responsive drug release.

Near-infrared (NIR) light-triggered drug release systems are promising for drug delivery applications in view of the advantages of NIR light, which include high tissue penetration and low damage. In this report, we developed nanogels (NGs) by supramolecular self-assembly from adamantine (AD)-conjugated copolymer, poly[poly(ethylene glycol)monomethyl ether metharcylate]-co-poly(N-(2-hydroxypropyl)methacrylamide)-co-poly(N-adamantan-1-yl-2-methacrylamide) (PPEGMA-co-PHPMA-co-PADMA), and β-cyclodextrin (β-CD)-functionalized poly(amidoamine) (PAMAM) dendrimer based on the host–guest interaction of the AD and β-CD moieties, and they were used to encapsulate indocyanine green (ICG) and doxorubicin (DOX) for combined photothermal-chemotherapy. NGs simultaneously loading ICG and DOX (DINGs) showed significant photothermal effects and stimuli-triggered drug release under NIR laser irradiation by the photothermal-induced relaxation or dissociation of the NGs. In vitro cytotoxicity evaluation of DINGs under NIR irradiation demonstrated the synergistic effects of hyperthermia, photothermal-triggered drug release, and chemotherapy. In vivo investigation revealed their high accumulation in tumor tissue and significant tumor growth suppression under NIR irradiation. These NIR light-triggered drug release NGs represent efficient and promising anticancer drug vectors for the combined photothermal-chemotherapy of cancer to maximize therapeutic efficacy and minimize side effects.