ABSTRACT
Biodegradable periodic mesoporous organosilica (BPMO) has recently emerged as a promising type of mesoporous silica-based nanoparticle for biomedical applications. Like mesoporous silica nanoparticles (MSN), BPMO possesses a large surface area where various compounds can be attached. In this work, we attached boronophenylalanine (10BPA) to the surface and explored the potential of this nanomaterial for delivering boron-10 for use in boron neutron capture therapy (BNCT). This cancer therapy is based on the principle that the exposure of boron-10 to thermal neutron results in the release of a-particles that kill cancer cells. To attach 10BPA, the surface of BPMO was modified with diol groups which facilitated the efficient binding of 10BPA, yielding 10BPA-loaded BPMO (10BPA-BPMO). Surface modification with phosphonate was also carried out to increase the dispersibility of the nanoparticles. To investigate this nanomaterial's potential for BNCT, we first used human cancer cells and found that 10BPA-BPMO nanoparticles were efficiently taken up into the cancer cells and were localized in perinuclear regions. We then used a chicken egg tumor model, a versatile and convenient tumor model used to characterize nanomaterials. After observing significant tumor accumulation, 10BPA-BPMO injected chicken eggs were evaluated by irradiating with neutron beams. Dramatic inhibition of the tumor growth was observed. These results suggest the potential of 10BPA-BPMO as a novel boron agent for BNCT.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Boron Compounds/chemistry , Metal Nanoparticles/administration & dosage , Neoplasms/drug therapy , Organosilicon Compounds/chemistry , Phenylalanine/chemistry , Apoptosis , Cell Proliferation , Humans , Metal Nanoparticles/chemistry , Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.
Subject(s)
DNA Breaks/radiation effects , Iodine/chemistry , Nanoparticles/chemistry , Neoplasms/pathology , Organic Chemicals/chemistry , Silicon Dioxide/chemistry , Spheroids, Cellular/radiation effects , Apoptosis/radiation effects , Cell Line, Tumor , DNA Breaks, Double-Stranded/radiation effects , Humans , Nanoparticles/ultrastructure , Organic Chemicals/chemical synthesis , Porosity , Silicon Dioxide/chemical synthesis , X-RaysABSTRACT
Biodegradable periodic mesoporous organosilica (BPMO) nanoparticles have emerged as a promising type of nanocarrier for drug delivery, given the biodegradable feature is advantageous for clinical translation. In this paper, we report synthesis and characterization of daunorubicin (DNR) loaded BPMO. DNR was loaded onto rhodamine B-labeled BPMO that contain tetrasulfide bonds. Tumor spheroids and chicken egg tumor models were used to characterize the activity in biological settings. In the first experiment we examined the uptake of BPMO into tumor spheroids prepared from ovarian cancer cells. BPMO were efficiently taken up into tumor spheroids and inhibited their growth. In the chicken egg tumor model, intravenous injection of DNR-loaded BPMO led to the elimination of ovarian tumor. Lack of adverse effect on organs such as lung appears to be due to excellent tumor accumulation of BPMO. Thus, DNR-loaded BPMO represents a promising nanodrug compared with free DNR currently used in cancer therapy. OK.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Daunorubicin/pharmacology , Nanoparticles/chemistry , Organosilicon Compounds/pharmacology , Ovarian Neoplasms/drug therapy , Animals , Antibiotics, Antineoplastic/chemistry , Cell Proliferation/drug effects , Chickens , Daunorubicin/chemistry , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Carriers/pharmacology , Drug Delivery Systems , Female , Humans , Nanoparticles/metabolism , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Organosilicon Compounds/chemistry , Organosilicon Compounds/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Particle Size , Porosity , Surface Properties , Tumor Cells, CulturedABSTRACT
Herein hybrid silica nanoparticles have been engineered to direct the sequential delivery of multiple chemotherapeutic drugs in response to external stimuli such as variations in pH. The nanocarriers consist of conventional MCM-41-type nanoparticles, which have been functionalised with an organic ligand (or stalk) grafted onto the external surface. The stalk is designed to "recognise" a complementary molecule, which serves as a "cap" to block the pores of the nanoparticles. First, camptothecin is introduced into the pores by diffusion prior to capping the pore apertures via molecular recognition. The cap, which is a derivative of 5-fluorouracil, serves as a second cytotoxic drug for synergistic chemotherapy. In vitro tests revealed that negligible release of the drugs occurred at pH 7.4, thus avoiding toxic side effects in the blood stream. In contrast, the stalk/cap complex is destabilised within the endolysosomal compartment (pH 5.5) of cancer cells, where release of the drugs was demonstrated. Furthermore, this environmentally responsive system exhibited a synergistic effect of the two drugs, where the pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo within the pores led to essentially complete elimination of breast cancer cells.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Delivery Systems , Fluorouracil/pharmacology , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , Fluorouracil/chemistry , Humans , MCF-7 Cells , Molecular Structure , Optical Imaging , Particle Size , Surface Properties , Tumor Cells, CulturedABSTRACT
The current chapter highlights the use of chorioallantoic membrane (CAM) of fertilized chicken egg for the characterization of nanoparticles applied in cancer nanomedicine. The CAM assay represents a promising alternative to mouse models in term of costs, ease of use, rapidity and ethical issues in particular for the screening of nanoformulations. Hence, the features of nanoparticles including blood retention, biocompatibility, active targeting or tumor accumulation, angiogenic activity, drug delivery and tumor elimination might be simply evaluated via the CAM model. In particular, in this model, embryo organs and morphology, CAM vasculature and blood cells, transplanted tumors on CAM were typically monitored and used for the evaluation of the nanomaterials. With the above advantages, the CAM assay, as highly valuable in vivo model, could be used regularly in pharmaceutical industries.
Subject(s)
Chorioallantoic Membrane/drug effects , Drug Delivery Systems , Nanoparticles , Neoplasms , Animals , Biological Assay , Chick EmbryoABSTRACT
Despite the versatility of periodic mesoporous organosilicas (PMOs), the bactericide capacity of these hybrid platforms has seldom been explored. Herein, we describe the synthesis of large-pore phenylene-bridged PMOs, mesostructured by polyion complex (PIC) micelles (PICPMOs) incorporating an antibiotic, neomycin B. A key feature of this approach is that the bioactive molecules are directly encapsulated within the PICPMOs during their formation. The engineered PICPMOs exhibit a well-ordered hexagonal mesophase with a molecular-scale crystallinity and large mesopores (8 nm), which facilitates pH-triggered delivery of the drug. The results obtained with a pathogenic Escherichia coli strain clearly demonstrate the potential of such PICPMOs for antibacterial applications.