A thermo-responsive PCL/PEG analogue copolymer (PCL-[b-P(MEO2MA-co-OEGMA)]2) with a lower critical solution temperature (LCST) of 40.4 °C at an MEO2MA/OEGMA molar ratio of 87 : 13 was designed and synthesized. The copolymer was subsequently labeled by coupling with fluorescein isothiocyanate (FITC). Thermo-responsive magnetic PCL-[b-P(MEO2MA-co-OEGMA)]2/Mn0.6Zn0.4Fe2O4 (MZF) complex micelles were prepared by a self-assembly method. Doxorubicin (DOX) was loaded into the magnetic complex micelles as a model drug, and the DOX-MZF-micelles showed well-controlled thermo-responsive release both at externally fixed temperatures and in the presence of an alternating magnetic field (AMF). Both the blank polymer micelles and the magnetic complex micelles exhibited excellent stability in normal saline and serum. Based on the detection of the FITC fluorescence signal, the micelles were found to be effectively labeled by FITC. Furthermore, the biological toxicity of micelles was studied in vitro and in vivo. In vitro toxicity studies to evaluate cell viability and cell toxicity were performed by employing WST-1 and LDH release assays using HL7702 cells, respectively. In vivo biotoxicity studies were conducted in ICR mice through a series of tests: general conditions, body weight shifts, serum biochemistry profiles, and organ coefficient tests. All the biological toxicity results obtained from the blank polymer micelles and the magnetic complex micelles indicated their good biocompatibility and nontoxicity. The in vivo biodistribution studies of the FITC-labeled magnetic complex micelles were performed in the ICR mice. The copolymer was cleared by the kidney and spleen, while the MZF nanoparticles were cleared by the liver in time, causing no adverse effects on organisms. The thermo-responsive magnetic complex micelles were shown to be an ideal nanocarrier for anticancer drug delivery in terms of controlled release, stability, biocompatibility and safety.

A thermo-responsive PCL/PEG analogue copolymer (PCL-[b-P(MEO2MA-co-OEGMA)]2) with a lower critical solution temperature (LCST) of 40.4 °C at an MEO2MA/OEGMA molar ratio of 87 : 13 was designed and synthesized. The copolymer was subsequently labeled by coupling with fluorescein isothiocyanate (FITC). Thermo-responsive magnetic PCL-[b-P(MEO2MA-co-OEGMA)]2/Mn0.6Zn0.4Fe2O4 (MZF) complex micelles were prepared by a self-assembly method. Doxorubicin (DOX) was loaded into the magnetic complex micelles as a model drug, and the DOX-MZF-micelles showed well-controlled thermo-responsive release both at externally fixed temperatures and in the presence of an alternating magnetic field (AMF). Both the blank polymer micelles and the magnetic complex micelles exhibited excellent stability in normal saline and serum. Based on the detection of the FITC fluorescence signal, the micelles were found to be effectively labeled by FITC. Furthermore, the biological toxicity of micelles was studied in vitro and in vivo. In vitro toxicity studies to evaluate cell viability and cell toxicity were performed by employing WST-1 and LDH release assays using HL7702 cells, respectively. In vivo biotoxicity studies were conducted in ICR mice through a series of tests: general conditions, body weight shifts, serum biochemistry profiles, and organ coefficient tests. All the biological toxicity results obtained from the blank polymer micelles and the magnetic complex micelles indicated their good biocompatibility and nontoxicity. The in vivo biodistribution studies of the FITC-labeled magnetic complex micelles were performed in the ICR mice. The copolymer was cleared by the kidney and spleen, while the MZF nanoparticles were cleared by the liver in time, causing no adverse effects on organisms. The thermo-responsive magnetic complex micelles were shown to be an ideal nanocarrier for anticancer drug delivery in terms of controlled release, stability, biocompatibility and safety.

Linear and star-shaped polylactides (PLA) with similar molecular weights of each arm are synthesized via ring-opening polymerization of LA with 3-butyn-1-ol and pentaerythritol as initiators, respectively. By solution blending of equivalent mass of poly(L-lactic acid)s (PLLAs) and poly(D-lactic acid)s (PDLAs), perfect PLA stereocomplexes (scPLAs) are prepared and confirmed by WAXD and FTIR analysis. Effect of chain architectures on stereocomplex crystallization is investigated by studying the non-isothermal and isothermal crystallization of linear and star-shaped polylactide stereocomplexes. In dynamic DSC and POM test, star-shaped PLLA (4sPLLA)/PDLA and PLLA/star-shaped PDLA (4sPDLA) stereocomplexes reach rapid crystallization and higher crystallinity due to larger spherulite density of star-shaped chain and excellent chain mobility of linear chain. In isothermal crystallization test, much faster crystallization and less crystallization half-time is obtained with the increase of star-shaped chain. Meanwhile, 4sPLLA/PDLA and PLLA/4sPDLA are found to have the highest crystallinity, suggesting limitation of too much star-shaped chain for 4sPLLA/4sPDLA and restriction of linear chain in nucleation capacity for PLLA/PDLA. The results reveal that star-shaped chain has an important influence on the crystallization of scPLAs.

To minimize the loading level of the char-forming phosphorus based flame retardants in the poly(lactic acid) (PLA) with reduced flammability, we have developed the flame-retarded PLA nanocomposites by melt blending method incorporating organically modified montmorillonite (OMMT) and aluminium diethylphosphinate (AlPi) additives. The influence of AlPi and OMMT on flame retardancy and thermal stability of PLA was thoroughly investigated by means of the limiting oxygen index (LOI), UL94 test, cone calorimeter, X-ray diffraction (XRD), thermogravimetric analysis and scanning electronic microscopy (SEM). The experimental results show that the PLA/AlPi/OMMT system has excellent fire retardancy. The LOI value increases from 19% for pristine PLA to 28% for the flame-retarded PLA. Cone calorimeter analysis of the PLA/AlPi/OMMT exhibits a reduction in the peak heat release rate values by 26.2%. Thermogravimetric analysis and SEM of cone calorimeter residues indicate that OMMT significantly enhances the thermal stability, promotes char-forming and suppresses the melt dripping. The research of this study implies that the combining of the flame retardant and organoclay results in a synergistic effect. In addition, the flame-retarded PLA nanocomposite also exhibits notable increase in the impact strength and the elongation at break.

Dendritic block copolymers with different chain length of poly(ε-caprolactone) (PCL) and poly(2-(dimethyl-amino)ethylmethacrylate) (PDMAEMA) were prepared and investigated as non-viral vectors for gene transfection in vitro and in vivo. Gel retardation analysis showed that all these dendritic copolymers could completely retard the mobility of DNA at and above an N/P ratio of 2.5/1. Dynamic light scattering analysis revealed that, at and above an N/P ratio of 5/1, these dendritic copolymers strongly condensed DNA into nanoscale polyplexes with average sizes ranging from about 50–160 nm and positive surface charges ranging from +13.4 to +30.3 mV. In vitro transfection tests using the plasmid encoding green fluorescence protein as gene reporter indicated that dendritic PCL-b-PDMAEMA copolymers were capable of transfecting MCF-7 and SKOV-3 cells, yielding comparable or higher transfection efficiencies in the absence or presence of serum when compared to 25 kDa branched polyethylenimine (bPEI) or 50 kDa PDMAEMA homopolymer as positive controls. Moreover, by intravenous injection of the polyplexes of these dendritic copolymers into SKOV-3 tumor-bearing nude mice, detectable transgene expression was observed in the tumor and other organs. These dendritic copolymers exhibited low in vitro cytotoxicity against MCF-7 and SKOV-3 cells with >80% viable cells at the tested polymer concentration below 25 μg mL−1 and also caused no death of the mice in vivo at a dose of 0.75 mg kg−1. The results manifested that dendritic PCL-b-PDMAEMA copolymers have high potential as safe and efficient gene delivery vectors.

•We prepared a new T2 MRI contrast agent using Mn,Zn-doped ferrite nanocrystals.•The MZF-loaded nanomicelles exhibit high r2 relaxivity value and low cytotoxicity.•The micellar contrast agent shows great potential in the tumor diagnosis in vivo.Superparamagnetic nanoparticles can be used as contrast agents for magnetic resonance imaging (MRI), which improve sensitivity and enhance biological information imaging at tissue, cellular or even molecular levels. In this study, manganese and zinc-doped superparamagnetic ferrite nanoparticles were used to form MRI contrast agent for tumor imaging. Hydrophobic Mn0.6Zn0.4Fe2O4 (MZF) nanocrystals with mean diameter of about 8 nm were synthesized in organic phase and then transferred into water to self-assemble into small clusters inside micelles with the help of biocompatible and amphiphilic star–block copolymers. The MZF-loaded micellar nanocomposites are superparamagnetic and could serve as a new T2 MRI contrast agent in cancer diagnosis. The new MRI contrast agent shows a low cytotoxicity in human hepatoma cell line, HepG2, and a high r2 relaxivity value. Thus, it could improve sensitivity of tumor imaging and be promising MRI contrast agent for tumor theranostic applications.

Monodispersed MnxZn1–xFe2O4 magnetic nanoparticles of 8 nm are synthesized and encapsulated in amphiphilic block copolymer for development of the hydrophilic magnetic nanoclusters (MNCs). These MNCs exhibit superparamagnetic characteristics, high specific absorption rate (SAR), large saturation magnetization (Ms), excellent stability, and good biocompatibility. MnFe2O4 and Mn0.6Zn0.4Fe2O4 are selected as optimum compositions for the MNCs (MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC) and employed for magnetic fluid hyperthermia (MFH) in vitro. To ensure biosafety of MFH, the parameters of alternating magnetic field (AMF) and exposure time are optimized with low frequency, f, and strength of applied magnetic field, Happlied. Under optimized conditions, MFH of MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC result in cancer cell death rate up to 90% within 15 min. The pathway of cancer cell death is identified as apoptosis, which occurs in mild hyperthermia near 43 °C. Both MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC show similar efficiencies on drug-sensitive and drug-resistant cancer cells. On the basis of these findings, those MnxZn1–xFe2O4 nanoclusters can serve as a promising candidate for effective targeting, diagnosis, and therapy of cancers. The multimodal cancer treatment is also possible as amphiphilic block copolymer can encapsulate, in a similar fashion, different nanoparticles, hydrophobic drugs, and other functional molecules.Keywords: cell apoptosis; magnetic fluid hyperthermia; magnetic nanoclusters; self-assembly; specific absorption rate

•Star-block copolymer micelles were prepared for temperature-triggered drug release.•We optimized the LCST to match the specific temperature of clinical hyperthermia.•The thermoresponsive micelles exhibit excellent response to the temperature changes.•Drug-loaded micelles could be uptaken by HepG2 cells and inhibit cell proliferation.Biodegradable and thermoresponsive star-block copolymer micelles were prepared and optimized for temperature-triggered drug release. The star-block poly(ε-caprolactone)-block-poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate) with lower critical solution temperature (LCST) of 42.8 °C was chosen to self-assemble into micelles for doxorubicin (DOX) loading. For comparison, the non-thermoresponsive star-block poly(ε-caprolactone)-block-poly(ethylene glycol) micelles with similar composition and diameter were also used to load DOX. The thermoresponsive micelles exhibit an excellent temperature-triggered drug release behavior and pulsed response to the temperature switching between 25 °C (below the LCST) and 45 °C (above the LCST). The cytotoxicity assay confirmed the effective growth inhibition for HepG2 cells induced by DOX-loaded thermoresponsive micelles, while the blank micelles had low cytotoxicity and good biocompatibility. The confocal laser scanning microscopy suggested that the DOX-loaded micelles could internalize into cytoplasm and cell nucleus of HepG2 cells. The thermoresponsive star-block copolymer micelles can potentially be used in the controlled drug delivery applications.

•Dendritic copolymer self-assembled into complex micelles with bimodal distribution.•Drug release from the complex micelles could be controlled by altering the pH values.•Drug-loaded micelles could be uptaken by cancer cells and inhibit cell proliferation.Amphiphilic dendritic star-block copolymer PCL-b-PDMAEMA composed of poly(ε-caprolactone) and poly(2-(N,N-dimethylamino)ethyl methacrylate) was synthesized successfully. In an aqueous solution, the copolymer could simultaneously self-assemble into unimolecular micelles and multimolecular mielles with mean diameters of about 28 nm and 190 nm, respectively. Dynamic light scattering measurements of these copolymer micelles showed bimodal size distribution. in vitro drug release behavior of the complex micelles loading camptothecin indicated that the rate of drug release could be effectively controlled by altering the pH values of the environment. The cytotoxicity assay confirmed the low cytotoxicity of the complex micelles and the significant drug efficacy. The confocal laser scanning microscopy demonstrated that the drug-loaded micelles could penetrate the cell membrane and be internalized into cytoplasm and cell nucleus of HeLa cells. Thus, the pH-responsive dendritic PCL-b-PDMAEMA micelles could be promising drug delivery vehicles for pharmaceutical and biomedical applications.

A thermo-responsive PCL/PEG analogue copolymer (PCL-[b-P(MEO2MA-co-OEGMA)]2) with a lower critical solution temperature (LCST) of 40.4 °C at an MEO2MA/OEGMA molar ratio of 87:13 was designed and synthesized. The copolymer was subsequently labeled by coupling with fluorescein isothiocyanate (FITC). Thermo-responsive magnetic PCL-[b-P(MEO2MA-co-OEGMA)]2/Mn0.6Zn0.4Fe2O4 (MZF) complex micelles were prepared by a self-assembly method. Doxorubicin (DOX) was loaded into the magnetic complex micelles as a model drug, and the DOX-MZF-micelles showed well-controlled thermo-responsive release both at externally fixed temperatures and in the presence of an alternating magnetic field (AMF). Both the blank polymer micelles and the magnetic complex micelles exhibited excellent stability in normal saline and serum. Based on the detection of the FITC fluorescence signal, the micelles were found to be effectively labeled by FITC. Furthermore, the biological toxicity of micelles was studied in vitro and in vivo. In vitro toxicity studies to evaluate cell viability and cell toxicity were performed by employing WST-1 and LDH release assays using HL7702 cells, respectively. In vivo biotoxicity studies were conducted in ICR mice through a series of tests: general conditions, body weight shifts, serum biochemistry profiles, and organ coefficient tests. All the biological toxicity results obtained from the blank polymer micelles and the magnetic complex micelles indicated their good biocompatibility and nontoxicity. The in vivo biodistribution studies of the FITC-labeled magnetic complex micelles were performed in the ICR mice. The copolymer was cleared by the kidney and spleen, while the MZF nanoparticles were cleared by the liver in time, causing no adverse effects on organisms. The thermo-responsive magnetic complex micelles were shown to be an ideal nanocarrier for anticancer drug delivery in terms of controlled release, stability, biocompatibility and safety.

A thermo-responsive PCL/PEG analogue copolymer (PCL-[b-P(MEO2MA-co-OEGMA)]2) with a lower critical solution temperature (LCST) of 40.4 °C at an MEO2MA/OEGMA molar ratio of 87:13 was designed and synthesized. The copolymer was subsequently labeled by coupling with fluorescein isothiocyanate (FITC). Thermo-responsive magnetic PCL-[b-P(MEO2MA-co-OEGMA)]2/Mn0.6Zn0.4Fe2O4 (MZF) complex micelles were prepared by a self-assembly method. Doxorubicin (DOX) was loaded into the magnetic complex micelles as a model drug, and the DOX-MZF-micelles showed well-controlled thermo-responsive release both at externally fixed temperatures and in the presence of an alternating magnetic field (AMF). Both the blank polymer micelles and the magnetic complex micelles exhibited excellent stability in normal saline and serum. Based on the detection of the FITC fluorescence signal, the micelles were found to be effectively labeled by FITC. Furthermore, the biological toxicity of micelles was studied in vitro and in vivo. In vitro toxicity studies to evaluate cell viability and cell toxicity were performed by employing WST-1 and LDH release assays using HL7702 cells, respectively. In vivo biotoxicity studies were conducted in ICR mice through a series of tests: general conditions, body weight shifts, serum biochemistry profiles, and organ coefficient tests. All the biological toxicity results obtained from the blank polymer micelles and the magnetic complex micelles indicated their good biocompatibility and nontoxicity. The in vivo biodistribution studies of the FITC-labeled magnetic complex micelles were performed in the ICR mice. The copolymer was cleared by the kidney and spleen, while the MZF nanoparticles were cleared by the liver in time, causing no adverse effects on organisms. The thermo-responsive magnetic complex micelles were shown to be an ideal nanocarrier for anticancer drug delivery in terms of controlled release, stability, biocompatibility and safety.

Dendritic block copolymers with different chain length of poly(ε-caprolactone) (PCL) and poly(2-(dimethyl-amino)ethylmethacrylate) (PDMAEMA) were prepared and investigated as non-viral vectors for gene transfection in vitro and in vivo. Gel retardation analysis showed that all these dendritic copolymers could completely retard the mobility of DNA at and above an N/P ratio of 2.5/1. Dynamic light scattering analysis revealed that, at and above an N/P ratio of 5/1, these dendritic copolymers strongly condensed DNA into nanoscale polyplexes with average sizes ranging from about 50–160 nm and positive surface charges ranging from +13.4 to +30.3 mV. In vitro transfection tests using the plasmid encoding green fluorescence protein as gene reporter indicated that dendritic PCL-b-PDMAEMA copolymers were capable of transfecting MCF-7 and SKOV-3 cells, yielding comparable or higher transfection efficiencies in the absence or presence of serum when compared to 25 kDa branched polyethylenimine (bPEI) or 50 kDa PDMAEMA homopolymer as positive controls. Moreover, by intravenous injection of the polyplexes of these dendritic copolymers into SKOV-3 tumor-bearing nude mice, detectable transgene expression was observed in the tumor and other organs. These dendritic copolymers exhibited low in vitro cytotoxicity against MCF-7 and SKOV-3 cells with >80% viable cells at the tested polymer concentration below 25 μg mL−1 and also caused no death of the mice in vivo at a dose of 0.75 mg kg−1. The results manifested that dendritic PCL-b-PDMAEMA copolymers have high potential as safe and efficient gene delivery vectors.