Folate modified nanoparticles for targeted co-delivery chemotherapeutic drugs and imaging probes for ovarian cancer

Ovarian cancer has been the leading cause of death worldwide in gynecologic malignancy mainly due to the lack of ultrasensitive diagnosis approaches at its early stage and high cytotoxicity of anticancer drugs to normal cells. In an attempt to overcome the problems, a co-delivery system of folic acid (FA) modified nanoparticles were developed for early diagnosis and to maximize the therapeutic outcome. In the present study, we formulated a diblock copolymer of methoxy poly (ethylene glycol)-b-poly (ecaprolactone)( mPEG-b-PCL) polymer micelles, and FA was further conjugated to endow micelles with active targeted capacity. Then paclitaxel (PTX) and superparamagnetic iron oxide (SPIO) were encapsulated in the core of micelles. The in vitro tumor cell targeting capability of FA-NP/SPIO/PTX and NP/SPIO/PTX nanoparticles was assessed by confocal laser scanning microscopy (CLSM) with human ovarian cancer (SKOV3 cells) which overexpresses FA receptor. Quantitative analysis showed the amount of intracellular Fe in cells incubated with FA-NP/SPIO/PTX nanoparticles was about 13fold higher than withNP/SPIO/PTX nanoparticles. The imaging contrast capability of FA-NP/ SPIO/PTX nanoparticles as a sensitive MRI probe was evaluated by a 3 T clinicalMRimaging scanner. The T-2 -weighted imaging of cells incubated with targeting nanoparticles was found to have more sensitive imaging enhancement effect on the SKOV3 cells than non-targeting nanoparticles. Furthermore, the antitumor efficiency of targeting nanoparticles was approximately 5-fold higher than that of their counterparts, which further affirmed the feasibility of attaining the higher therapeutic efficacy of antitumor drugs while minimizing damage to healthy cells. The targeting nanoparticles exhibited the biphasic release characteristic in vitro. The results indicated that folatemodified nanoparticles could achieve high targeting specificity, high efficiency of delivery drug and excellent imaging enhancement. Therefore, the targeting nanoplatform has good prospects in noninvasively detecting early ovarian tumors, maximizing the therapeutic efficiency and real-time monitoring of therapeutic response, which can make it possible to lengthen patients' survival and ultimately achieve the goal of individualized medicine for ovarian cancer in the near future.