NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

Show details

Protoporphyrin IX and IR-820 fluorophore–encapsulated organically modified silica nanoparticles

PpIX/IR-820–doped ORMOSIL NPs
, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: August 7, 2012.

Chemical name:Protoporphyrin IX and IR-820 fluorophore–encapsulated organically modified silica nanoparticles
Abbreviated name:PpIX/IR-820–doped ORMOSIL NPs
Synonym:
Agent Category:Nanoparticles
Target:Non-targeted
Target Category:Non-targeted
Method of detection:Optical imaging
Source of signal / contrast:IR-820
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
No structure available.

Background

[PubMed]

Protoporphyrin IX (PpIX) and IR-820 fluorophore–encapsulated organically modified silica nanoparticles (ORMOSIL NPs), abbreviated as PpIX/IR-820–doped ORMOSIL NPs, were synthesized by Qian et al. for two-photon photodynamic therapy (PDT) and optical imaging (1).

PDT has been investigated for several decades as an alternative to chemotherapy and radiotherapy for tumor treatment (2, 3). PDT involves the use of light, a photosensitizer (PS), and tissue oxygen. Under light excitation, PS transfers its energy to neighboring oxygen molecules, resulting in the generation of singlet oxygen (1O2) and other cytotoxic reactive oxygen species, which leads to apoptosis and necrosis of cancer cells. To date, most PSs developed for PDT are hydrophobic, aggregate easily in blood, and exhibit poor tumor selectivity (1, 2). One technique to overcome these issues is to link PSs to or encapsulate them in nanocarriers (4, 5).

Nanocarriers have been synthesized with diverse nanomaterials such as polymers, metals, semi-conductors, and silica. ORMOSIL NPs have shown great potential as an ideal nano-platform for theranostic applications because of their unique properties (6-8). First, ORMOSIL NPs are chemically inert, and the silica matrix porosity is resistant to swelling or changes in varying pH conditions. Second, ORMOSIL NPs can be loaded with both hydrophilic and hydrophobic payloads and protected from degradation by the bio-environment. PSs can be encapsulated in the monomeric form without loss of activity. Third, ORMOSIL NPs are mesoporous, which allows controlled release of the encapsulated biomolecules. Fourth, ORMOSIL NPs are able to accumulate selectively in tumors through the enhanced permeability and retention effects of tumor tissues. Finally, the size, shape, porosity, and monodispersibility of the ORMOSIL NPs can be controlled during preparation, and their surfaces can be functionalized with various chemical groups and/or targeting biomolecules.

The most recent studies on PDT with ORMOSIL NPs have focused on the targeted delivery for two-photon PDT in deep tissues and on the multimodal applications within one NP platform, such as the combination of magnetic resonance imaging, optical imaging, and PDT (2, 3). For imaging and therapeutic purposes, Qian et al. synthesized PpIX-doped and near-infrared (NIR) dye IR-820–doped ORMOSIL NPs (1). PpIX is a photosensitizer currently used in the clinic. The investigators tested the feasibility of using the NPs for optical imaging and PDT of tumor cells under two-photon excitation (1).

Synthesis

[PubMed]

PpIX/IR-820–doped ORMOSIL NPs were synthesized by Qian et al. in the nonpolar core of Aerosol-OT/DMSO/water micelles (1). The NPs were further modified with polyethylene glycol. At the end of synthesis, both PpIX-doped and IR-820–doped ORMOSIL NPs had a narrow size distribution with an average diameter of ~25 nm and ~42 nm, respectively. Both types of NPs showed a spherical morphology with a mesoporous matrix on their surface under transmission electron microscopy. The strongest linear absorption band of PpIX-doped ORMOSIL NPs was ~404 nm, and its decaying tail extended into the 600–650 nm range. Spectral studies on IR-820–doped ORMOSIL NPs showed absorption and emission values of 700–900 nm and 836–850 nm, respectively. The amount of each payload per NP was not reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Two-photon imaging of PpIX-doped ORMOSIL NPs in HeLa cells was performed with a two-photon confocal microscope under 800-nm femtosecond laser excitation after incubation of HeLa cells with PpIX-doped ORMOSIL NPs for 2 h at 37°C (1). Confocal microscopy showed bright red fluorescent signal distributed within the cells, which was from the intracellular PpIX. There was no obvious aggregation of the NPs in cell culture conditions.

The two-photon PDT efficacy of PpIX-doped ORMOSIL NPs was analyzed with HeLa cells and with 2 min irradiation under 800-nm laser from the confocal microscope (1). The HeLa cells treated with PpIX-doped ORMOSIL NPs showed no morphological changes immediately after 2 min irradiation. At 8 min after irradiation, the HeLa cells became round, and bubble-like changes were observed on the cell surface. These changes became more obvious over time, and at 15 min after irradiation, some cells started to show signs of necrosis. For the control HeLa cells without treatment, no obvious changes in their morphology were observed after irradiation. These results indicate that the two-photon excited PpIX led to the death of HeLa cells.

The imaging capacity of IR-820–doped ORMOSIL NPs in deep tissues was evaluated with a liquid phantom (1). The phantom was composed of intralipid and black ink, which had optical properties (especially in the NIR spectra) similar to typical human tissue. The IR-820–doped ORMOSIL NPs were buried in the phantom solution at different depths (0.5 cm, 1 cm, and 1.5 cm). NIR images showed that the NIR signal intensity decreased with increasing depth of the samples. The signal at a depth of 1.5 cm was still strong (280 units), and the image showed a high contrast without broadening compared to that at a depth of 0.5 cm.

Animal Studies

Rodents

[PubMed]

The in vivo imaging efficiency of IR-820–doped ORMOSIL NPs was evaluated by Qian et al. with three animal models (n =1 mouse/model) (1). The investigators first applied the NPs for mouse brain imaging. The NPs (0.5 μl/location) were injected into the brain of a black mouse at depths of ~1 mm, 2 mm, 3 mm, and 4 mm, respectively. The four distinct NIR fluorescent points inside the brain could be clearly distinguished with optical imaging. The brightness of the fluorescence signal decreased at deeper locations.

Qian et al. then applied the NPs for sentinel lymph node (SLN) mapping (1). The NPs (0.1 ml) were injected intradermally into the forepaw pad of a nude mouse. At 4 min after injection, the fluorescence signal was observed at an axillary node, and the signal became stronger over time. At 20 min after injection, the signal intensity in the lymph node reached the maximum. The lymph node, which was dissected, emitted NIR fluorescence with a peak wavelength of 850 nm, consistent with that of IR-820–doped ORMOSIL NPs. These results suggested that IR-820–doped ORMOSIL NPs could be used as an NIR optical probe for in vivo SLN mapping.

Qian et al. further applied the NPs for tumor imaging (1). The NPs were injected via the tail vein into a nude mouse bearing a subcutaneous tumor xenograft (HeLa cells). At 5 h after injection, distinct NIR signals were observed in the liver, tumor, and tail. At 24 h, NIR fluorescence was still clear and distinct in the tumor and liver. After 10 days, the fluorescence could be observed clearly in the tumor, but not in the liver. After 30 days, the NPs in the tumor were cleared, and no more NIR signal could be observed. These results indicated that the NPs could home on mouse tumor xenographs, and that, due to the protection of the ORMOSIL NPs, the fluorescent dye remained stable for a relatively long time. No effects of the NPs were observed on the weight, shape, eating, drinking, or exploratory behavior of the mouse. For the control mouse without NP treatment, only autofluorescence was detected.

Other Non-Primate Mammals

[PubMed]

No references are currently available.

Non-Human Primates

[PubMed]

No references are currently available.

Human Studies

[PubMed]

No references are currently available.

References

1.
Qian J., Wang D., Cai F., Zhan Q., Wang Y., He S. Photosensitizer encapsulated organically modified silica nanoparticles for direct two-photon photodynamic therapy and in vivo functional imaging. Biomaterials. 2012;33(19):4851–60. [PubMed: 22484045]
2.
Allison R.R., Bagnato V.S., Sibata C.H. Future of oncologic photodynamic therapy. Future Oncol. 2010;6(6):929–40. [PubMed: 20528231]
3.
Couleaud P., Morosini V., Frochot C., Richeter S., Raehm L., Durand J.O. Silica-based nanoparticles for photodynamic therapy applications. Nanoscale. 2010;2(7):1083–95. [PubMed: 20648332]
4.
Baba K., Pudavar H.E., Roy I., Ohulchanskyy T.Y., Chen Y., Pandey R.K., Prasad P.N. New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug. Mol Pharm. 2007;4(2):289–97. [PMC free article: PMC2667689] [PubMed: 17266331]
5.
Verhille M., Couleaud P., Vanderesse R., Brault D., Barberi-Heyob M., Frochot C. Modulation of photosensitization processes for an improved targeted photodynamic therapy. Curr Med Chem. 2010;17(32):3925–43. [PubMed: 20858211]
6.
Ohulchanskyy T.Y., Roy I., Goswami L.N., Chen Y., Bergey E.J., Pandey R.K., Oseroff A.R., Prasad P.N. Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer. Nano Lett. 2007;7(9):2835–42. [PubMed: 17718587]
7.
Hocine O., Gary-Bobo M., Brevet D., Maynadier M., Fontanel S., Raehm L., Richeter S., Loock B., Couleaud P., Frochot C., Charnay C., Derrien G., Smaihi M., Sahmoune A., Morere A., Maillard P., Garcia M., Durand J.O. Silicalites and Mesoporous Silica Nanoparticles for photodynamic therapy. Int J Pharm. 2010;402(1-2):221–30. [PubMed: 20934496]
8.
Cheng S.H. andLo, L.W. Inorganic nanoparticles for enhanced photodynamic cancer therapy. Curr Drug Discov Technol. 2011;8(3):250–68. [PubMed: 21644924]

Views

  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this page (72K)
  • MICAD Summary (CSV file)

Search MICAD

Limit my Search:


Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...