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Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin.

ABSTRACT: We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe(3)O(4). We prepared the PHNPs by controlled oxidation of Fe NPs at 250 degrees C followed by acid etching. The opening pores ( approximately 2-4 nm) facilitated the cisplatin diffusion into the cavity of the hollow structure. The porous shell was stable in neutral or basic physiological conditions, and cisplatin escape from the cavity through the same pores was a diffusion-controlled slow process with t(1/2) = 16 h. However, in low pH (<6) conditions, the pores were subject to acidic etching, resulting in wider pore gaps and faster release of cisplatin with t(1/2) < 4 h. Once coupled with Herceptin to the surface, the cisplatin-loaded hollow NPs could target to breast cancer SK-BR-3 cells with IC(50) reaching 2.9 muM, much lower than 6.8 muM needed for free cisplatin. Our model experiments indicate that the low pH-responsive PHNPs of Fe(3)O(4) can be exploited as a cisplatin delivery vehicle for target-specific therapeutic applications.

SUBMITTER: Cheng K

PROVIDER: S-EPMC2739121 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin.

Cheng Kai K Peng Sheng S Xu Chenjie C Sun Shouheng S

Journal of the American Chemical Society 20090801 30

We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe(3)O(4). We prepared the PHNPs by controlled oxidation of Fe NPs at 250 degrees C followed by acid etching. The opening pores ( approximately 2-4 nm) facilitated the cisplatin diffusion into the cavity of the hollow structure. The porous shell was stable in neutral or basic physiological conditions, and cisplatin escape from the cavity through the same pores was a diffusion-controlled slow pr ...[more]

PMID: 19722635

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Project description:Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO2 NPs had an average diameter of 130?±?5?nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO2 NPs. Zeta potential of these redox-responsive particles was -23?±?1?mV at pH?6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446?±?6?m2?g-1 and the average diameter of the pores was 2.3?±?0.5?nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9?±?0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14?days in phosphate buffered saline (PBS) at pH?6 and in the presence of 10?mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24?h with the maximum uptake of c.a. 2.1?±?0.3% and 5.2?±?0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO2 NPs) were nontoxic to MCF-7 cells after incubation for 24?h within the concentration range of 0-1000??g?ml-1. DOX-loaded GSH-sensitive nanospheres containing 6??g?ml-1 of DOX killed c.a. 51% of MCF-7 cells after 24?h while TEOS HMSiO2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3?T3 fibroblasts shows that intact GSH-sensitive HMSiO2 NPs did not show any toxic effects on these cells with the concentrations equal or <125??g?ml-1.

Dataset Information

Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin.

Publications

Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin.

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