Encapsulation of Upconversion Nanoparticles in Periodic Mesoporous Organosilicas.

(1) Background: Nanomedicine has recently emerged as a promising field, particularly for cancer theranostics. In this context, nanoparticles designed for imaging and therapeutic applications are of interest. We, therefore, studied the encapsulation of upconverting nanoparticles in mesoporous organosilica nanoparticles. Indeed, mesoporous organosilica nanoparticles have been shown to be very efficient for drug delivery, and upconverting nanoparticles are interesting for near-infrared and X-ray computed tomography imaging, depending on the matrix used. (2) Methods: Two different upconverting-based nanoparticles were synthesized with Yb3+-Er3+ as the upconverting system and NaYF4 or BaLuF5 as the matrix. The encapsulation of these nanoparticles was studied through the sol-gel procedure with bis(triethoxysilyl)ethylene and bis(triethoxysilyl)ethane in the presence of CTAB. (3) Results: with bis(triethoxysilyl)ethylene, BaLuF5: Yb3+-Er3+, nanoparticles were not encapsulated, but anchored on the surface of the obtained mesoporous nanorods BaLuF5: Yb3+-Er3+@Ethylene. With bis(triethoxysilyl)ethane, BaLuF5: Yb3+-Er3+ and NaYF4: Yb3+-Er3+nanoparticles were encapsulated in the mesoporous cubic structure leading to BaLuF5: Yb3+-Er3+@Ethane and NaYF4: Yb3+-Er3+@Ethane, respectively. (4) Conclusions: upconversion nanoparticles were located on the surface of mesoporous nanorods obtained by hydrolysis polycondensation of bis(triethoxysilyl)ethylene, whereas encapsulation occurred with bis(triethoxysilyl)ethane. The later nanoparticles NaYF4: Yb3+-Er3+@Ethane or BaLuF5: Yb3+-Er3+@Ethane were promising for applications with cancer cell imaging or X-ray-computed tomography respectively.

Efficient Photodynamic Therapy of Prostate Cancer Cells through an Improved Targeting of the Cation-Independent Mannose 6-Phosphate Receptor.

The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs.

Porphyrin-based bridged silsesquioxane nanoparticles for targeted two-photon photodynamic therapy of zebrafish xenografted with human tumor.

BACKGROUND: Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine. AIMS: In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small-sized nanoparticles were functionalized with PEG and mannose (PORBSNs-mannose) in order to target breast tumors in vivo. METHODS AND RESULTS: The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two-photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs-mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two-photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation. CONCLUSION: We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs-mannose injected in the blood stream of zebrafish xenografted with human tumors.

Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles for two-photon photodynamic therapy or photoacoustic imaging.

Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles (BSPOR and BSPHT) were prepared. Their endocytosis in MCF-7 cancer cells was shown with two-photon excited fluorescence (TPEF) imaging. With two-photon excited photodynamic therapy (TPE-PDT), BSPOR was more phototoxic than BSPHT, which in contrast displayed a very high signal for photoacoustic imaging in mice.

Fluorescent periodic mesoporous organosilica nanoparticles dual-functionalized via click chemistry for two-photon photodynamic therapy in cells.

The synthesis of ethenylene-based periodic mesoporous organosilica nanoparticles for two-photon imaging and photodynamic therapy of breast cancer cells is described. A dedicated two-photon absorbing fluorophore possessing four triethoxysilyl groups and having large two-photon absorption in the near IR region, and azidopropyltriethoxysilane were incorporated into the structure. The mesoporous nanoparticles of 100 nm diameter were further functionalized by means of click chemistry with a propargylated fluorescent bromo-quinoline photosensitizer able to generate singlet oxygen. The photophysical properties and two-photon absorption properties of the nanoparticles were investigated evidencing complementary contribution of the two dyes. Both dyes contribute to the two-photon absorption response of the mesoporous nanoparticles while efficient FRET from the two-photon fluorophore to the quinoline sensitizer is observed. The dual-functionalized nanoparticles were incubated with MCF-7 breast cancer cells. Two-photon confocal imaging demonstrated the endocytosis of the nanoparticles within cancer cells. Moreover, brief two-photon irradiation (3 scans of 1.57 s) at 760 nm at high laser power (3 W) was shown to induce 40% of cancer cell death demonstrating the potential of the dual-functionalized mesoporous organosilica nanoparticles for two-photon photodynamic therapy.

Synthesis of disulfide-based biodegradable bridged silsesquioxane nanoparticles for two-photon imaging and therapy of cancer cells.

Biodegradable bridged silsesquioxane (BS) nanomaterials for two-photon-excited (TPE) imaging and therapy of breast cancer cells were described. A versatile synthesis was developed to design monodisperse tetra-alkoxysilylated diamino-diphenylbutadiene or Zn-porphyrin-based nanospheres of 30 to 50 nm.

Porphyrin-functionalized mesoporous organosilica nanoparticles for two-photon imaging of cancer cells and drug delivery.

The synthesis of a zinc porphyrin derivative possessing eight triethoxysilyl groups was performed through a CuAAC-click reaction. This porphyrin was covalently entrapped in ethenylene-bridged mesoporous organosilica nanoparticles which efficiently allowed performing doxorubicin delivery and two-photon imaging of breast cancer cells.