Drug Nanoparticle Carrier for Cancer Chemotherapy Figure 6. The survival as a function of time and life span of H22 tumor-bearing mice model that received different treatments. (A) The survival as a function of time of the tumor-bearing mice of the DOX-PGMNPs-M group. (B)There is a significantly increased life span of the tumor- bearing mice of the DOX-PGMNPs-M group. doi:10.1371/journal.pone.0040388.g006 (tumor) by an EMF force. DOX concentrations in tumors of mice from the DOX-PGMNPs-M group were significantly higher than those from the DOX-PGMNPs group or the DOX group after injection 0.5 hr. This led to the therapeutic potency and efficacy of the DOX-PGMNPs-M. In contrast, there was no difference of DOX concentration in the tumors between the groups treated with DOX or DOX-PGMNPs (Fig. 3). This could attributed to enhanced permeability and retention (EPR) effect of DOX- PGMNPs in the liver and spleen and the drug controlled release behavior. Therefore, it did not lead to a higher DOX accumu- lation in the tumor of DOX-PGMNPs compared with free DOX. The data of the concentration of DOX in the livers, tumors and spleen of DOX-PGMNPs also is according to the results. The efficiency of tumor growth inhibition was substantially more pronounced in mice of the DOX-PGMNPs group than in mice of the DOX group, although there have no significantly difference between DOX-PGMNPs-M group and DOX-PGMNPs-m group. This could imply that the growth-inhibitory effect of the DOX- PGMNPs (Figs. 5 and 6) is not only related to the DOX concentration but also to the DOX-releasing behavior from DOX-PGMNPs in vivo. Although our studies on H22 cells indicated that PGMNPs displayed no significant toxicity (or minor toxicity) in vitro, a direct cytotoxic effect of the PGMNPs on the tumor cells in vivo cannot be excluded. The data of life span of mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX (74.869.95, 66.1613.5, and 31.363.31 days) were showed that there is significantly efficiency for tumor treatment of DOX- PGMNPs group compared to the DOX group. Using an EMF to locate these drug-loading carriers, the efficiency for tumor treatment will be better. In summary, DOX-PGMNPs binding and releasing were efficient in vitro investigations and the results show that most of DOX-PGMNPS were cleared by RES and targeted to liver and spleen. This indicates that the PGMNPs constitute highly attractive nanocarriers and offer a promising perspective for an EMF-guided delivery of anticancer therapeutics and integration in cancer treating protocols. Although additional research is needed to further demonstrate that PGMNPs are indeed general drug carriers, the possibility that a single carrier could be used to transport multiple classes of drugs to their desired targets makes these PGMNPs versatile therapeutic tools. Furthermore, pharma- cokinetic profiles obtained to date certainly warrant further investigation of these PGMNPs. This technology has the potential to provide the long-felt need for a precise, consistent, and efficient drug delivery method that can be used in numerous medical applications. PLOS ONE | www.plosone.org 6 October 2012 | Volume 7 | Issue 10 | e40388