The pH-sensitive tertiary amino groups were introduced to synthesize temperature and pH dual-sensitive degradable polyaspartamide derivatives (phe/DEAE-g-PHPA) containing pendant aromatic structures and ionizable tertiary amino groups. The thermo/pH-responsive behavior of phe/DEAE-g-PHPA polymer can be tuned by adjusting the graft copolymer composition. Due to the pH sensitivity of the phe/DEAE-g-PHPA-g-mPEG polymer with hydrophilic long PEG chain, the micelles and the anticancer drug-loaded micelles were prepared by a quick pH-changing method without using toxic organic solvent. The obtained polymeric micelles, paclitaxel-loaded micelles and doxorubicin-loaded micelles were stable under physiological conditions. Both the drug-loaded micelles showed much faster release at pH 5 than at pH 7.4. The doxorubicin-loaded micelles showed obvious and better anticancer activity against both HepG2 and HeLa cells than free doxorubicin. Thus these nontoxic, dual thermo- and pH-sensitive phe/DEAE-g-PHPA-g-mPEG micelles may be a promising anticancer drug delivery system. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 879–888

The development of novel thermo- and photo-dual-responsive biodegradable polymeric micelles based on amphiphilic polyaspartamide derivatives (NB-g-PHPA-g-mPEG) for anticancer drug delivery is reported. The obtained polymers containing hydrophobic photocleavable o-nitrobenzyl groups exhibit thermo- and photosensitivity. The micelles and paclitaxel-loaded micelles based on the thermo- and photo-dual-sensitive polymers were prepared by a quick heating method without using toxic organic solvent. The paclitaxel release from the drug-loaded micelles can be triggered under photoirradiation. Enhancement of the anticancer activity against HeLa cells was observed for paclitaxel-loaded NB-g-PHPA-g-mPEG micelles after light irradiation, while the empty NB-g-PHPA-g-mPEG micelles with or without irradiation did not show any toxicity. Therefore, the thermo- and photo-dual-responsive NB-g-PHPA-g-mPEG micelles have a promising future applied as a light controlled drug delivery system for anticancer drugs. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2855–2863

Biodegradable and thermosensitive polyaspartamide derivatives containing pendant azide groups P(Asp-Az)_X-HPAs were synthesized from poly(l-succinimide) via the ring-opening reaction with 2-azidoethylamine (Az) and 5-hydroxypentylamine (HPA). Then hydrophobic phenethyl (PEA) and imidazole (IMZ) moieties were introduced successfully with very high reaction efficiency above 90% to the side chains of P(Asp-Az)_X-HPA by click reaction to obtain thermoresponsive polyaspartamide derivatives containing pendant aromatic rings P(Asp-Az)_X-HPA-PEAs and the thermo/pH-responsive polyaspartamide derivatives containing pendant imidazole rings P(Asp-Az)_X-HPA-IMZs, respectively. The thermoresponsive behaviors of P(Asp-Az)_X-HPA-PEAs and P(Asp-Az)_X-HPA-IMZs were confirmed by dynamic light scattering (DLS) and transmittance measurements, and the cloud point can be tuned by designed amounts of azide groups and can be further adjusted by the grafting molar percentage of hydrophobic phenethyl or imidazole moieties to the side chains of P(Asp-Az)_X-HPA via click chemistry. The pH-responsive behavior of P(Asp-Az)_X-HPA-IMZs can also be tuned. These results indicate that the obtained polyaspartamide-based functional polymers can be further functionalized with hydrophilic long PEG chain and/or targeted moieties via click chemistry for drug delivery. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1296–1303

A novel kind of graft polymer poly(aspartic acid)-ethanediamine-g-adamantane/methyloxy polyethylene glycol (Pasp-EDA-g-Ad/mPEG) was designed and synthesized for drug delivery in this study. The chemical structure of the prepared polymer was confirmed by proton NMR. The obtained polymer can self-assemble into micelles which were stable under a physiological environment and displayed pH- and β-cyclodextrin (β-CD)-responsive behaviors because of the acid-labile benzoic imine linkage and hydrophobic adamantine groups in the side chains of the polymer. The doxorubicin (Dox)-loaded micelles showed a slow release under physiological conditions and a rapid release after exposure to weakly acidic or β-CD environment. The in vitro cytotoxicity results suggested that the polymer was good at biocompatibility and could remain Dox biologically active. Hence, the Pasp-EDA-g-Ad/mPEG micelles may be applied as promising controlled drug delivery system for hydrophobic antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1387–1395

Biodegradable amphiphilic ABC Y-shaped triblock copolymer (MPBC) containing PEG, PBLA, and PCL segments was synthesized via the combination of enzymatic ring-opening polymerization (ROP) of epsilon-caprolactone, ROP of BLA-N-carboxyanhydride and click chemistry, where PEG, PBLA, and PCL are poly(ethylene glycol), poly(benzyl-l-aspartate), and polycaprolactone, respectively. Propynylamine was employed as ROP initiator for the preparation of alkynyl-terminated PBLA and methyloxy-PEG with hydroxyl and azide groups at the chain-end was used as enzymatic ROP initiator for synthesis of monoazido-midfunctionalized block copolymer mPEG-b-PCL. The subsequent click reaction led to the formation of Y-shaped asymmetric heteroarm terpolymer MPBC. The polymer structures were characterized by different analyses. The MPBC terpolymer self-assembled into micelles and physically encapsulated drug doxorubicin (DOX) to form DOX-loaded micelles, which showed good stability and slow drug release. In vitro cytotoxicity study indicated that the MPBC micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3346–3355

Novel pH and reduction dual-sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy-poly(ethylene glycol)-b-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl) imidazole-l-aspartamide)] [mPEG-SS-P(BLA-co-APILA), MPBA] synthesized by a combination of ring-opening polymerization and side-chain reaction. The pH/reduction-responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX-loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX-loaded micelles showed retarded drug release in phosphate-buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX-loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual-responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1771–1780

The preparation, characterization, release, and in vitro cytotoxicity of a biodegradable polymeric micellar formulation of paclictaxel (PTX) were investigated. The micelles based on thermosensitive and degradable amphiphilic polyaspartamide derivatives containing pendant aromatic structures (phe-g-PHPA-g-mPEG) were prepared by a quick heating method without using toxic organic solvent. Dynamic light-scattering results show that the micelles are stable upon dilution under physiological conditions and the destabilization of the micelles is pH-dependent and the phe-g-PHPA-g-mPEG polymers are biodegradable. PTX was loaded into the phe-g-PHPAs-g-mPEG micelles with encapsulation efficiency of >90%, resulting in a high drug loading content (up to 29%). PTX-loaded micelles had a mean size around 70 nm with narrow size distribution (polydispersity index, <0.1). The PTX-loaded micelles showed sustained drug release and obvious anticancer activity similar to Taxol against HepG2 cells, whereas blank micelles were nontoxic. The present results suggest that the thermosensitive and biodegradable phe-g-PHPA-g-mPEG micelles are a promising delivery system for the hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3917–3924

A novel class of thermoresponsive and reduction-sensitive polymer, p(PEG-MEMA-co-Boc-Cyst-MMAm), containing disulfide linkages and removable hydrophobic tert-butyloxycarbonyl side chains was synthesized. The cloud points (CP) of p(PEG-MEMA-co-Boc-Cyst-MMAm) in water determined by UV/VIS spectrometer were between 20 °C and 57 °C, which shows that the CP can be tuned by adjusting the copolymer composition. Moreover, the thermosensitive polymers p(PEG-MEMA-co-Boc-Cyst-MMAm) formed stable nanoparticles in neutral aqueous medium, but rapidly destabilized in an reductive environment mimicking the intracellular space making them suitable for cytoplasmic drug delivery. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5989–5997, 2009