Various approaches for the synthesis of mesoporous silicate nanoparticles (MSN) with large pore (LP) diameters (in the range of 3-50 nm) are reviewed in this article. The work also covers the ...construction of magnetic analogues of large pore-mesoporous silica nanoparticles (LPMMSN) and their biomedical applications. The constructed materials exhibit vast potential for application in the loading and delivery of large drug molecules and biomolecules. Literature reports on the application of LPMSN and LPMMSN materials for the adsorption and delivery of proteins, enzymes, antibodies, and nucleic acids are covered in depth, which exemplify their highly potent characteristics for use in drug and biomolecule delivery to diseased tissues.
Zap 'em! Multifunctionalized mesoporous silica nanoparticles induce significant reduction of tumor size upon two‐photon excitation in the near‐infrared region while being nontoxic under daylight ...illumination. These nanoparticles were further tested for in vivo two‐photon photodynamic therapy (TPE‐PDT). A 70 % regression of tumor size after a single treatment was observed in athymic mice bearing tumor xenografts.
Periodic mesoporous organosilica nanorods and nanospheres are synthesized from 1,4‐bis(triethoxysilyl)ethylene and bis(3‐ethoxysilylpropyl)disulfide. The nanosystems present the long‐range order of ...the hexagonal nanostructure. They are degraded in simulated physiological conditions. The loading and release of doxorubicin with these nanosystems are both pH dependent. These nanoparticles are endocytosed by breast cancer cells and are very efficient for doxorubicin delivery in these cells.
Periodic mesoporous organosilica nanoparticles emerge as promising vectors for nanomedicine applications. Their properties are very different from those of well‐known mesoporous silica nanoparticles ...as there is no silica source for their synthesis. So far, they have only been synthesized from small bis‐silylated organic precursors. However, no studies employing large stimuli‐responsive precursors have been reported on such hybrid systems yet. Here, the synthesis of porphyrin‐based organosilica nanoparticles from a large octasilylated metalated porphyrin precursor is described for applications in near‐infrared two‐photon‐triggered spatiotemporal theranostics. The nanoparticles display unique interconnected large cavities of 10–80 nm. The framework of the nanoparticles is constituted with J‐aggregates of porphyrins, which endows them with two‐photon sensitivity. The nanoparticle efficiency for intracellular tracking is first demonstrated by the in vitro near‐infrared imaging of breast cancer cells. After functionalization of the nanoparticles with aminopropyltriethoxysilane, two‐photon‐excited photodynamic therapy in zebrafish is successfully achieved. Two‐photon photochemical internalization in cancer cells of the nanoparticles loaded with siRNA is also performed for the first time. Furthermore, siRNA targeting green fluorescent protein complexed with the nanoparticles is delivered in vivo in zebrafish embryos, which demonstrates the versatility of the nanovectors for biomedical applications.
The synthesis of porous porphyrin‐based organosilica nanoparticles is described. The porphyrins form J aggregates that allow two‐photon excitation of the nanoparticles. Two‐photon photodynamic therapy of tumors implanted in zebrafish is very efficient. Two‐photon photochemical internalization in cancer cells is demonstrated and siRNA targeting green fluorescent protein is also successfully delivered in the zebrafish model.
The use of magnetic nanoparticles for sensing and theranostics of cancer has grown substantially in the last decade. Since the pioneering studies, which reported magnetic nanoparticles for ...bio-applications more than fifteen years ago, nanomaterials have increased in complexity with different shapes (nanoflowers, nanospheres, nanocubes, nanostars etc.) and compositions (e.g. core-shell) of nanoparticles for an increase in the sensitivity (imaging or sensing) and efficiency through synergistic treatments such as hyperthermia and drug delivery. In this review, we describe recent examples concerning the use of magnetic nanoparticles for bio-applications, from the surface functionalization methods to the development of cancer sensors and nanosystems for magnetic resonance and other imaging methodologies. Multifunctional nanosystems (nanocomposites, core shell nanomaterials) for theranostic applications involving treatments such as hyperthermia, photodynamic therapy, targeted drug delivery, and gene silencing are also described. These nanomaterials could be the future of medicine, although their complexity raises concerns about their safety.
In this review, the use of mesoporous silica nanoparticles for photodynamic therapy (PDT) applications is described for the year 2017. Since the pioneering work in 2009, nanosystems involving ...mesoporous silica nanoparticles have gained in complexity with a sophisticated core-shell system able to perform multi-imaging and multi-therapies, not only for cancer diseases but also for anti-microbial therapy, atherosclerosis, or Alzheimer disease. Near-infrared, excitation light based on up-converting systems, X-rays or persistent luminescent systems are described for deeper tissue treatments.
Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2‐photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose‐functionalized pSiNPs ...can be vectorized to MCF‐7 human breast cancer cells through a mannose receptor‐mediated endocytosis mechanism to provide a 3‐fold enhancement of the 2‐photon PDT effect.
Coherent two‐photon‐excited (TPE) therapy in the near‐infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by ...a 3D spatial resolution of 1 µm3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE‐NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well‐established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side‐effect therapies via TPE‐NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two‐photon absorbers for drug delivery and diagnosis. Currently, most light‐actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two‐photon‐sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE‐NIR ultrasensitive diagnosis and therapy.
Two‐photon‐absorbing (2hνA) nanoparticles provide safer cancer treatment opportunities than current therapies lacking spatial and temporal selectivities thanks to their 3D spatial resolution of 1 µm3 and very low scattering. Herein, porous and nonporous 2hνA silica, organosilica, and gold‐silica nanoparticles are described for bioimaging, drug delivery, and photodynamic therapy via photolysis, energy transfer, and electron transfer mechanisms.
The properties of mesoporous silica nanoparticles (MSN) (biocompatibility, surface area, particle diameter, mesoporous structure, and ease of functionalization) are reviewed regarding their benefits ...for the construction of cancer‐targeting drug delivery systems, with an overview of literature reports within this research area. Intrinsic properties characteristic of tumor tissues (enhanced permeability and retention effect, overexpressed receptors, and acidic extracellular pH) are further discussed which can be utilized for cancer targeting. Recent literature reports are also accounted concerning MSN‐based cancer targeting that takes advantage of characteristics of the tumor environment and also nanotherapeutics capable of stimulus (acidification, exposure to light irradiation, magnetic field) responsive drug delivery. Finally, gene therapy approaches for cancer treatment and MSN‐based gene delivery vectors are reviewed. The research on mesoporous silicates possesses great potential for the development of complex multipurpose nanotherapeutics for simultaneous application in effective targeted treatment and imaging of cancer tissues.
Nanotherapeutics are designed and constructed from mesoporous silica nanoparticles for the targeted treatment of cancer based on characteristics of tumor tissues. The picture shows drug delivery triggered by the acidic extracellular environment of cancer, endocytosis of the drug carrier, and intracellular release of cargo drugs.
New therapy development is critically needed for ovarian cancer. We used the chicken egg CAM assay to evaluate efficacy of anticancer drug delivery using recently developed biodegradable PMO ...(periodic mesoporous organosilica) nanoparticles. Human ovarian cancer cells were transplanted onto the CAM membrane of fertilized eggs, resulting in rapid tumor formation. The tumor closely resembles cancer patient tumor and contains extracellular matrix as well as stromal cells and extensive vasculature. PMO nanoparticles loaded with doxorubicin were injected intravenously into the chicken egg resulting in elimination of the tumor. No significant damage to various organs in the chicken embryo occurred. In contrast, injection of free doxorubicin caused widespread organ damage, even when less amount was administered. The lack of toxic effect of nanoparticle loaded doxorubicin was associated with specific delivery of doxorubicin to the tumor. Furthermore, we observed excellent tumor accumulation of the nanoparticles. Lastly, a tumor could be established in the egg using tumor samples from ovarian cancer patients and that our nanoparticles were effective in eliminating the tumor. These results point to the remarkable efficacy of our nanoparticle based drug delivery system and suggests the value of the chicken egg tumor model for testing novel therapies for ovarian cancer.
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