An amphiphilic polymer DLPE-S-S-MPEG was synthesized and employed with PCL to prepare two-component reduction-sensitive lipid–polymer hybrid nanoparticles (SLPNPs) for in vitro and in vivo delivery of a hydrophobic anticancer drug (Doxorubicin, DOX). Insensitive lipid–polymer hybrid nanoparticles (ILPNPs) were prepared as a control. The mean sizes of the LPNPs ranged from 100 nm to 120 nm. The TEM observations showed that the LPNPs have spherical morphologies with homogeneous distribution. The disulfide bond of DLPE-S-S-MPEG was cleaved by dithiothreitol (DTT), which resulted in the disassembly of SLPNPs and triggered the release of encapsulated DOX. The in vitro cytotoxicities of DOX/LPNPs against HeLa cells, HepG2 cells and COS-7 cells were studied. It was demonstrated that DOX/SLPNPs showed higher cytotoxicity against HeLa cells and HepG2 cells than DOX/ILPNPs, but showed a slight difference in the case of COS-7 cells. CLSM observation and FCM measurement further confirmed that the introduction of S–S bonds caused fast intracellular release of DOX from SLPNPs. Moreover, compared with DOX/ILPNPs and free DOX, DOX/SLPNPs exhibited higher antitumor activity. Both DOX/SLPNPs and DOX/ILPNPs showed lower cardiac toxicity and kidney toxicity than free DOX, which were confirmed by histological and immunohistochemical analyses. The tissue distribution of DOX in mice exhibited that two kinds of DOX/LPNPs accumulated extensively in the liver and spleen, while free DOX accumulated mainly in the heart and kidney 12 h after injection. Two-component SLPNPs may be a promising drug delivery carrier for reduction-triggered delivery of DOX.

It is of great interest to monitor implants in real-time using non-invasive detecting techniques in interventional therapies or tissue regeneration. In this study, MRI-visible hydrogels that are pH sensitive, injectable and self-healing were prepared based on chitosan and PEG. The macromolecular chelator of Gd(III), Ch–DTPA, was synthesized by functionalization of chitosan with diethylene triamine pentaacetic acid (DTPA). The PEG end-capped with aryl aldehyde, PEG-DA, was prepared as a crosslinker. Based on the Schiff's base reaction, the hydrogels can be obtained quickly just by mixing the aqueous solutions of Ch–DTPA and PEG-DA at ambient temperature. The gelating procedure is pH sensitive, and the hydrogels exhibit self-healing in an environment with a pH value of 4.5–5.3. The morphology of the lyophilized gel was observed by SEM. In vitro release behavior of the hydrogel was tested also using rhodamine B as a model drug. The MRI contrast enhancement effect of Gd(III)-binding hydrogels was investigated both in vitro and in vivo on rats. The results revealed that the hydrogels showed strong signals on T1-weighted MR images, and the hydrogels could always be detected before complete biodegradation. Combining the histology observation, the developed in situ hydrogels are of potential in the application of long-term reporting of implants by MRI.

The biodegradable poly(5-methyl-5-methoxycarbonyl-1,3-dioxan-2-one-co-d,l-lactide) [poly(MMTC-co-d,l-LA)] copolymers were synthesized by the ring-opening copolymerization. The results show that the yield and molecular weight of copolymers are significantly influenced by reaction conditions. The chemical structure of the resultant copolymers was characterized by FTIR, 1H NMR and 13C NMR methods. Their molecular weight was measured by gel permeation chromatography (GPC). Study of monomer coreactivity ratios indicates that d,l-LA reacts faster than MMTC in the copolymerization. The enzymatic degradation of the polymers with various compositions was studied at 37 °C in pH = 8.6 Tris–HCl buffer solution in the presence of proteinase K. Their mechanical properties were also preliminarily investigated.

An amphiphilic polymer DLPE-S-S-MPEG was synthesized and employed with PCL to prepare two-component reduction-sensitive lipid–polymer hybrid nanoparticles (SLPNPs) for in vitro and in vivo delivery of a hydrophobic anticancer drug (Doxorubicin, DOX). Insensitive lipid–polymer hybrid nanoparticles (ILPNPs) were prepared as a control. The mean sizes of the LPNPs ranged from 100 nm to 120 nm. The TEM observations showed that the LPNPs have spherical morphologies with homogeneous distribution. The disulfide bond of DLPE-S-S-MPEG was cleaved by dithiothreitol (DTT), which resulted in the disassembly of SLPNPs and triggered the release of encapsulated DOX. The in vitro cytotoxicities of DOX/LPNPs against HeLa cells, HepG2 cells and COS-7 cells were studied. It was demonstrated that DOX/SLPNPs showed higher cytotoxicity against HeLa cells and HepG2 cells than DOX/ILPNPs, but showed a slight difference in the case of COS-7 cells. CLSM observation and FCM measurement further confirmed that the introduction of S–S bonds caused fast intracellular release of DOX from SLPNPs. Moreover, compared with DOX/ILPNPs and free DOX, DOX/SLPNPs exhibited higher antitumor activity. Both DOX/SLPNPs and DOX/ILPNPs showed lower cardiac toxicity and kidney toxicity than free DOX, which were confirmed by histological and immunohistochemical analyses. The tissue distribution of DOX in mice exhibited that two kinds of DOX/LPNPs accumulated extensively in the liver and spleen, while free DOX accumulated mainly in the heart and kidney 12 h after injection. Two-component SLPNPs may be a promising drug delivery carrier for reduction-triggered delivery of DOX.

It is of great interest to monitor implants in real-time using non-invasive detecting techniques in interventional therapies or tissue regeneration. In this study, MRI-visible hydrogels that are pH sensitive, injectable and self-healing were prepared based on chitosan and PEG. The macromolecular chelator of Gd(III), Ch–DTPA, was synthesized by functionalization of chitosan with diethylene triamine pentaacetic acid (DTPA). The PEG end-capped with aryl aldehyde, PEG-DA, was prepared as a crosslinker. Based on the Schiff's base reaction, the hydrogels can be obtained quickly just by mixing the aqueous solutions of Ch–DTPA and PEG-DA at ambient temperature. The gelating procedure is pH sensitive, and the hydrogels exhibit self-healing in an environment with a pH value of 4.5–5.3. The morphology of the lyophilized gel was observed by SEM. In vitro release behavior of the hydrogel was tested also using rhodamine B as a model drug. The MRI contrast enhancement effect of Gd(III)-binding hydrogels was investigated both in vitro and in vivo on rats. The results revealed that the hydrogels showed strong signals on T1-weighted MR images, and the hydrogels could always be detected before complete biodegradation. Combining the histology observation, the developed in situ hydrogels are of potential in the application of long-term reporting of implants by MRI.