Abstract
Superparamagnetic iron-oxide nanoparticle (SPION) has gained tremendous attention for drug delivery applications due to their unique properties. In this study, we developed a dual targeted delivery system with paclitaxel (PTX) and SPION co-loaded PLGA nanoparticles, modified with Pep-1 peptide (Pep-NP-SPION/PTX), to achieve magnetic targeting and active targeting for tumor treatment. SPION was synthesized by a co-precipitation method and was then encapsulated with PTX simultaneously into PLGA nanoparticles. After that, the non-complex was conjugated with Pep-1 through chemical modification. The resulting Pep-NP-SPION/PTX showed a spherical morphology and an average size of 100 nm. The enhancement cellular uptake of Pep-NP-SPION was demonstrated in in vitro through cell experiments. The IC50 value of Pep-NP-SPION/PTX and NP-SPION/PTX was determined to be 10.2 and 19.4 μg/mL, respectively. A biodistribution study showed that obvious higher accumulations of Pep-NP-SPION was observed in tumors, compared with that of non-targeting nanocomposites. Moreover, under the condition of a magnetic field, both NP-SPION and Pep-NP-SPION exhibited much higher tumor distribution. Furthermore, Pep-NP-SPION/PTX presented desirable in vivo anti-tumor effects based on active targeting and magnetic targeting characteristics. Altogether, Pep-NP-SPION/PTX can offer magnetic targeting and receptor mediated targeting to enhance the anti-tumor outcome.
Highlights
Current tumor chemotherapy still faces a major problem with the of lack of selectivity of drugs on tumor cells, which leads to a narrow therapeutic index of most anti-tumor drugs (Wong et al, 2016)
In order to reduce the toxicity of a chemotherapy drug at its minimum dose, specific nanoparticulate drug delivery systems, such as nanoparticle, liposome and polymeric micelle, could provide a non-invasive treatment strategy due to its passive targeting properties
Superparamagnetic iron-oxide nanoparticles (SPION) consisting of cores made of iron oxides, have been considered to be attractive in cancer theranostic applications, since they can be delivered to the required tissue through an external magnetic field (Hachani et al, 2016)
Summary
Current tumor chemotherapy still faces a major problem with the of lack of selectivity of drugs on tumor cells, which leads to a narrow therapeutic index of most anti-tumor drugs (Wong et al, 2016). After intravenous (i.v.) injection, Pep-NP-SPION/PTX was expected to accumulate at the tumor tissue in the presence of an external magnetic field and be internalized into tumor cells through IL-13Rα2 mediated endocytosis, which would reduce the uptake of Pep-NP-SPION/PTX by the MPS and enhance the anti-tumor efficiency of PTX. These physical-chemical properties of the dual targeted nanocarrier were systematically characterized. The in vitro and in vivo anti-tumor effect of Pep-NP-SPION/PTX was studied using a cell and subcutaneous xenograft tumor mice model, respectively
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