Abstract
An ideal carrier for chemotherapeutics delivery shall contain features such as cancer cell-targeting capability, low cytotoxicity and efficient killing effect on multiple drug resistant cancer cells. In this study, we proposed a novel nano-sized drug delivery system combining the advantages of: (1) NIR-triggered drug release; (2) magnetically-targeting and (3) magnetic resonance imaging (MRI) contrast. The drug carrier is mainly composed of poly-lactic-co-glycolic acid (PLGA), which is a highly biocompatible, biodegradable and US Food and Drug Administration (FDA)-approved materials for clinical uses. PLGA is widely used for drug delivery applications due to its advantages on protecting drug from loss of activity, reducing drug-associated cytotoxicity and improving drug stability. By utilizing single emulsion method, we have successfully encapsulated doxorubicin (a chemotherapeutic drug), superparamagnetic iron oxide nanoparticles (SPIONs) and gold nanorods (Au NRs) within the hydrophobic core of PLGA nanoparticles (NP). The size and surface potential of the resultant AFP were approximately 200 nm and -24 mV respectively. The prepared DOX@SPIONs/Au NRs/ PLGA nanoparticle(DOX@SAPP)were successfully verified with the following features, including: (1) Hydrophilic nanoparticle surface: the DOX@SAPP were covered with hydrophilic polyethylene glycol (PEG), which helps maintaining particle stability and may extend its in vivo circulation time. (2) Capability of loading of various theranostic materials: The loading contents for doxorubicin, SPIONs were 3.77% and 5.8% respectively. By tuning the feeding amount of dodecane-Au NRs (O.D. value 33, 100 and 300), PLGA nanoparticles with different Au NRs loading content (1.31%, 2.73% and 8.19%) can be prepared. (3) Well colloidal stability: the prepared DOX@SAPP were stable up to 3 days in various mediums such as: water, PBS and 25% FBS DMEM medium. The size of DOX@SAPP was not changed significantly in PBS for 15 days. (4) Magnetically-assisted drug delivery and MRI contrast: the DOX@SAPP exhibits superparamagnetism with the saturation magnetization of 3.04 emu/g. The cellular uptake of DOX@SAPP was greatly enhanced by the presence of external magnetic field. Cell-number dependent T2-weighing MRI was demonstrated from the DOX@SAPP -uptake cancer cells. The DOX@SAPP enters cells via endocytosis which can avoid the “drug pumping out” effect by multiple drug resistant cancer cells. Under the irradiation of NIR, the Au NRs-mediated photothermal effect effectively triggered rapid drug release from DOX@SAPP Finally, the combined photothermal- and chemo- therapeutic effect was successfully demonstrated on astrocytoma tumor cell line (ALTS1C1), human breast cancer cells (MCF7) and its multiple drug resistant strain (ADR-MCF7).