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Cisplatin-functionalized silica nanoparticles for cancer chemotherapy.

ABSTRACT: Cisplatin is used to treat a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including breast. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule and characterized in terms of size, shape, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as received silica nanoparticles ranged from 20 to 90 nm. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the live/dead stain, can be correlated with surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. Moreover, if verified by further studies, would indicate that cisplatin was attached to silica nanoparticles might prove to be useful in site-specific drug delivery.

SUBMITTER: Rejeeth C

PROVIDER: S-EPMC4451868 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Cisplatin-functionalized silica nanoparticles for cancer chemotherapy.

Rejeeth Chandrababu C Nag Tapas C TC Kannan Soundarapandian S

Cancer nanotechnology 20130720 6

Cisplatin is used to treat a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including breast. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule and characterized in terms of size, shape, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as received silica nanoparticles ranged from 20 to 90 nm. The results show ...[more]

PMID: 26069508

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Project description:PurposeNano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.MethodsSuperparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.Results800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM(-1)·s(-1). Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.ConclusionThis is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.

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Cisplatin-functionalized silica nanoparticles for cancer chemotherapy.

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Cisplatin-functionalized silica nanoparticles for cancer chemotherapy.

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