Preparation And Properties Of Liposomes-Coated Thermo-Sensitive Nanogels Via In Situ Liposomal Template Polymerization

In cancer treatment,chemotherapy is one of the main methods for clinical treatment.However,it is usually faced with some limitations,especially the nonspecific distribution of drugs,so it also has a strong toxicity to normal tissues.Chemophotothermal therapy has shown enormous potential in cancer treatment.To achieve the chemo-photothermal synergistic effect,an efficient nanoparticles system with the ability of simultaneous co-delivery of chemotherapeutic drug and photothermal agent as well as photothermal-triggered drug release,is highly desirable.In this paper,the liposome-coated P(NIPAm-co-AAm)thermo-responsive nanogel(NGs@lipo)was prepared based on in situ polymerization within liposome template.By adjusting the content of co-monomer AAm,the LCST of the internal thermosensitive gel could be adjusted to about 40 °C.NGs@lipo can effectively load the NIR dye indocyanine green(ICG)and doxorubicin hydrochloride(DOX).DOX was loaded by liposome active drug loading meathod which significantly increased the drug loading efficiency.The DOX/ICG coloaded hybrid nanogels,denoted as DINGs@lipo,integrated the desirable functions of PEGylated liposomes and thermosensitive nanogels.The PEGylated liposomes shell provided excellent storage,hemodynamic and fluorescence stabilities.Meanwhile,the thermosensitive P(NIPAMco-AAM)nanogels core endowed DI-NGs@lipo with volume phase transition temperature(VPTT)at about 40 °C,allowing the thermo-controlled transformation and drug release.Under the irradiation of NIR light,DI-NGs@lipo shows enhanced photothermal effect and can achieve rapid DOX release.In vitro cytotoxicity and cell uptake assays demonstrated that NGs@lipo had good biocompatibility and that DINGs@lipo could achieve synergistic therapeutic effects with chemotherapy and photothermotherapy under NIR light irradiation.Based on the above experiments,a temperature and pH-sensitive P(NIPAm-coAAc)hydrogel was prepared by radical solution polymerization.The apparent morphology and temperature sensitivity of the P(NIPAm-co-AAc)hydrogel were investigated.Thermal analyzer experiment results show that the LCST of hydrogel is 40 °C.At the above monomer ratio,a dual sensitive liposome-coated(P(NIPAm-coAAc))nanogel carrier(T/pH NGs@lipo)was prepared by in situ polymerization within liposome template.The UV-Vis spectrum and DSC experiments showed that T/pH NGs@lipo had phase change behavior at 40 °C.The change in particle size and drug release behavior at different temperatures and pH strongly demonstrated the dual sensitivity of T/pH NGs@lipo.Taken together,the NGs@lipo constructed in this project could be an effective nanoplatform to cancer treatment.