Targeted Pegylated Plga-Coated Prussian Blue Nanocomposite for Dual-Modality Pa/Mr Imaging and Synergistic Chemothermal Tumor Therapy

Abstract

To prepare a PEGylated poly (lactic-co-glycolic acid) (PLGA) targeting with folic acid (FA) coated Prussian blue nanoparticles (PB NPs) and paclitaxel (PTX), to construct multifunctional PLGA-PB-PTX-PEG-FA nanocomposite for both photoacoustic (PA) imaging, magnetic resonance imaging (MRI) and synergistic chemo-thermal tumor therapy. Paclitaxel (PTX)-loaded Folic acid (FA) targeted PEGylated PLGA nanoparticles encapsulating Prussian Blue (PB) (PLGA-PB-PTX-PEG-FA) nanocomposite was fabricated by a modified double emulsion (water/oil/water) evaporation process. The morphology, size, UV–vis–NIR absorbance spectra, Fourier transfer infrared (FTIR) spectrum were tested to evaluate the structural characterization of PLGA-PB-PTX-PEG-FA. Drug Loading and releasing of PLGA-PB-PTX-PEG-FA nanocomposite were assessed by high performance liquid chromatography (HPLC). Additionally, in vitro cell targeting and in vivo tumor targeting were verified by confocal laser scanning microscopy (CLSM) and vital fluorescence imaging (VFI) to assess the targeting effect of PLGA-PB-PTX-PEG-FA nanocomposite. The efficacy of the contrast agent for PA imaging and MRI was evaluated by in vitro and in vivo imaging of subcutaneous MDA-MB-231 tumor-bearing mice following tail intravenous injection of the contrast agent. Finally, to visualize the photothermal cytotoxicity of PLGA-PB-PTX-PEG-FA nanocomposite, MDA-MB-231 cells were incubated with PLGA-PB-PTX-PEG-FA nanocomposite in 96 well-plate for 2 h and were irradiated with or without NIR laser. CCK8 method was used to measure the viability of the cells. To study the photothermal effect and synergistic therapeutic efficacy, PLGA-PB-PTX-PEG-FA nanocomposite suspensions of various concentrations nanoparticle dispersions were exposed to a laser with the wavelength of 808 nm and the output power of 0.647W/cm2 for 10min in vitro or in vivo after vein intravenous injection. The highly dispersed PLGA-PB-PTX-PEG-FA nanocomposite with spherical morphology has good uniformity with an average hydrodynamic diameter of 236.6±55.04nm. Both PB and PLGA-PB-PTX-PEG-FA nanocomposite displayed a broad absorption band with a strong absorption peak at ∼702 nm. While the IR spectrum of the PLGA-PB-PTX-PEG-FA nanocomposite showed both the corresponded peaks of PLGA- PEG-FA and PB NPs. The results of drug loading efficiency and drug loading capacity tested by HPLC were 77.82% and 7.22%. The fast drug release from the nanocomposite in vitro with laser irradiation indicated the great potential as a controlled-release system for the anticancer drug. In vitro cell targeting and in vivo tumor targeting results, targeted group had obvious difference from non-targeted group and blank control group, which showed that good targeting effect to tumor cells or tumor in vivo. After the tail intravenous injection of the PLGA-PB-PTX-PEG-FA nanocomposite, the PA images and MR images of tumor of nude mice were significantly enhanced, while there were almost no distinct enhancement in non-targeted group and blank control group. The result of the photothermal cytotoxicity of PLGA-PB-PTX-PEG-FA nanocomposite showed that the viability of the cells of PLGA-PB-PTX-PEG-FA nanocomposite+Laser group was lowest. The results of photothermal conversion property of PLGA-PB-PTX-PEG-FA suggested the character of photothermal effect was positively correlated with the heating power and the nanoparticles concentration and exhibited good photostability. Upon near-infrared laser irradiation, the PLGA-PB-PTX-PEG-FA nanocomposite showed an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer. In conclusion, we prepared highly dispersed core-shell structure PLGA-PB-PTX-PEG-FA nanocomposite by coating PB NPs with PLGA-FA shell and then modifying with PEG. The prepared PLGA-PB-PTX-PEG-FA nanocomposite has good biocompatibility, excellent photo-thermal transformation capacity, and can enhance both PA imaging and MR imaging in vitro and in vivo. Furthermore, PLGA-PB-PTX-PEG-FA nanocomposite acts as a multifunctional drug delivery system with higher drug loading capacity and excellent drug controlled release-system. Finally, our result confirmed that PLGA-PB-PTX-PEG-FA nanocomposite has the ability of the synergistic therapeutic efficacy combined photothermal and chemical therapy effect, which further enhances the therapeutic efficacy to breast cancer.