Drug Loaded Plga Microspheres For Theranostic Applications

With the development of micro/nanotechnology, theranostic agent with both therapy and diagnosis functionalities has become a new research hotspot in cancer diagnosis and treatment in recent years. Dual-mode ultrasound (US)/magnetic resonance (MR) contrast agents have the ability to provide more comprehensive information to improve the accuracy of diagnosis. Recent advances in nanotechnology show that by double emulsion method, polymer NPs are able to easily incorporate two different contrast agents within one particle system, thereby allowing for the generation of contrast agents for dual mode US/MR imaging applications. Poly (D,L-lactic-co-gly colic acid)(PLGA) with excellent biocompatibility, biodegradability and high stability has been widely used in the construction of multifunctional theranostic agent.In chapter2, superparamagnetic Fe3O4nanoparticles-and anticancer drug doxorubicin (DOX)-loaded PLGA hollow microspheres (HMs) were synthesized, characterized and applied as dual-modal contrast agents for US/MR molecular imaging, respectively. The formed PLGA-FesO4-DOX HMs display good US imaging enhancement in vitro, as well as good MR imaging enhancement in vitro. The HMs are able to image mouse liver in vivo via MR imaging. Likewise, the loaded DOX in the HMs with a loading efficiency of12.5%is able to be released in a sustained manner with a higher initial release rate at acidic pH condition than at physiological pH condition. Importantly, MTT assay and cell morphology observation data reveal that the encapsulation of DOX within PLGA-Fe3O4-DOX HMs does not significantly compromise the therapeutic efficacy of the DOX drug. Taken together, the developed PLGA-Fe3O4-DOX HMs may be used as a theranostic agent for dual-mode US/MR imaging and drug delivery applications.In chapter3, a theranostic agent of PLGA-DOX-PEI-PEG-FA HMs were synthesized, characterized and applied as US imaging and pH-responsive targeted drug delivery vehicle for cancer treatment. SEM and CLSM imaging showed the core-shell structure of the PLGA-DOX-PEI-PEG-FA HMs with a PEI-PEG-FA polymer shell and a hollow capsule structured PLGA-DOX core. The PLGA-DOX-PEI-PEG-FA HMs displayed a pH-responsive release behavior. MTT assay shows that the PLGA-DOX-PEI-PEG-FA HMs can effectively kill KB cells. The cancer cell targeting efficiency of the PLGA-DOX-PEI-PEG-FA HMs was confirmed by flow cytometry. Besides the displayed good US imaging enhancement, the formed multifunctional HMs are able to target KB cells overexpressing high-affinity folic acid receptors and exert specific therapeutic efficacy to the KB cells, suggesting that the synthesized HMs may be used as a theranostic agent for targeted drug delivery and US imaging.