Hybrid Paclitaxel and Gold Nanorod-Loaded Human Serum Albumin Nanoparticles for Simultaneous Chemotherapeutic and Photothermal Therapy on 4T1 Breast Cancer Cells.
ACS Appl Mater Interfaces. 2015 Mar 13;
Authors: Peralta DV, Heidari Z, Dash S, Tarr MA
The use of human serum albumin nanoparticles (HSAPs) as a drug carrier system for cancer treatment has proven successful through current marketable clinical formulations. Despite this success, there is a current lack of multi-functional HSAPs which offer combinational therapies of more than one proven technique. Gold nanorods (AuNRs) have also shown medicinal promise due to their photothermal therapy capabilities. In this study, a desolvation and crosslinking approach was employed to successfully encapsulate gold nanorods into HSAPs simultaneously with the chemotherapeutic drug paclitaxel (PAC); forming PAC-AuNR-HSAPs with desirable overall particle sizes of 299 ± 6 nm. The loading efficiency of paclitaxel into PAC-AuNR-HSAPs reached up to 3μg PAC/mg HSA. The PAC-AuNR-HSAPs experienced photothermal heating; with the bulk particle solution reaching up to 46 ˚C after 15 minutes of near-IR laser exposure. This heat increase marked the successful attainment of the temperature necessary to cause severe cellular hyperthermia and necrosis. The encasement strategy facilitated a colloidal hybrid treatment system capable of enhanced permeability and retention effects, photothermal ablation of cancer cells, and release of the active paclitaxel of up to 188 ng (from PAC-AuNR-HSAPs created with 30 mg HSA) in a single 15 minute irradiation session. When treated with PAC-AuNR-HSAPs containing 20 µg PAC/mL particle solution, 4T1 mouse breast cancer cells experienced ~ 82% cell death without irradiation and ~ 94% cell death after just one irradiation session. The results for PAC-AuNR-HSAPs were better than that of free PAC, which only killed ~ 77% of the cells without irradiation and ~ 80% with irradiation. The hybrid particle system also lends itself to future customizable external functionalities via conjugated targeting ligands such as antibodies. Internal entrapment of patient tailored medication combinations are also possible with this combination treatment platform, which may result in improved quality of life for those undergoing treatment.
PMID: 25768122 [PubMed – as supplied by publisher]