Zeolitic Imidazole Framework/Silica Nanocomposite for Targeted Cancer Therapeutics: Comparative Study of Chemo-Drug Cisplatin (CPt) and Green Platinum (GPt) Efficacy.

A chemo-drug such as cisplatin is effective for cancer treatment but remains non-specific, is susceptible to drug resistance, and induces several side effects on organ systems. Zeolitic imidazolate framework-8, a type of MOF, has gained attention, including as a drug delivery method for targeted cancer therapeutics. In this study, ZIF-8/Silica nanocomposite was synthesized using a one-pot hydrothermal technique using the Stober technique. We studied the effect of phyto-synthesized GPt and chemo-drug cisplatin CPt on ZIF-8/Silica for targeted efficacy of cancer therapy. The texture, morphology, and chemical environment of Pt on ZIF-8/Silica were analyzed using different characterization techniques such as XRD, FT-IR, BET, diffuse reflectance spectroscopy, SEM-EDX, TEM, zeta potential, and TGA analysis. The isothermal behavior of CPt and GPt adsorption was investigated using isotherm models like Langmuir, Freundlich, and Temkin isotherm. The adsorption kinetics indicating the adsorption efficiency of GPt and CPt are influenced by the concentration of Pt complex and the adsorption sites of ZIF-8/Silica. A high entrapment efficiency and loading capacity of GPt (86% and 4.3%) and CPt (91% and 4.5%) were evident on ZIF-8/Silica. The nanocomposite showed a pH-sensitive Pt release using a dialysis membrane technique. For instance, a high release of GPt (93%) was observed under pH = 6.6 in 72 h, while the release reduced to 50% at pH 7.4 in 72 h. The anti-cancer activity of nanoformulations was studied in vitro using MCF7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) cells. The findings demonstrated that GPt is as effective as CPt; the EC50 value for MCF7 cells treated with ZIF-8/Silica/Cp/PEG was 94.86 µg/mL, whereas for ZIF-8/Silica/GPt/PEG it was 60.19 µg/mL.

Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus.

An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe3+ species were identified using diffuse reflectance spectroscopy. The large surface area (804 m2/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug's release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08-1 h), insulin/ferrisilicate ratios (0.125-1.0) and drug release rates at different pH were examined using the Korsmeyer-Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 µg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.

Insights of Platinum Drug Interaction with Spinel Magnetic Nanocomposites for Targeted Anti-Cancer Effect.

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe2O4/GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe2O4/silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn2+ species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt4+ species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe2O4/silica/cisplatin and MnFe2O4/GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death.

Anti-blastocystosis activity of antioxidant coated ZIF-8 combined with mesoporous silicas MCM-41 and KIT-6.

The biocompatible hybrid Zeolitic imidazolate framework-8 (ZIF-8)/structured silica nanocomposite can be loaded with antioxidants such as curcumin and resveratrol to offer multiple advantages of drug functionalization and structural stability. blastocystosis, an enteric parasite, has various outcomes and its treatment includes drugs which have side effects and do not result in a full cure. We aimed to design novel biocompatible nanocomposites containing natural antioxidant, resveratrol or curcumin and ZIF-8/mesoporous silica. We also assessed their anti-blastocystosis activities as bioactive novel nanocomposites. The nano-silica (MCM-41 and KIT-6) was synthesized using a hydrothermal technique and made composite with ZIF-8 using an ultrasonic technique. The antioxidants, curcumin and resveratrol, were loaded over ZIF-8/MCM-41 and ZIF-8/KIT-6 using a rotary evaporator technique to form novel nanocomposites with bioactive properties. The formulated nanocomposites were characterized. To test their biological activity, suspension of cultured blastocystosis cysts (subtype 3) were exposed to increasing concentrations of nanocomposites and the minimal lethal concentration of each nanocomposite was calculated. The bioactive nanocomposites (ZIF-8/KIT-6, ZIF-8/KIT-6/Resveratrol and ZIF-8/MCM-41/Curcumin) were formulated. Anti-blastocystosis activity of the tested nanocomposites was both dose and time dependent. ZIF-8/KIT-6/Resveratol showed the maximum percentage of growth inhibition (~ 100%) at a concentration of 500 µg/ml after 5 h of exposure. More than 90% of blastocystosis cysts' growth was significantly inhibited at all concentrations of ZIF-8/MCM-41/Curcumin, with different times of exposure, while it occurred only at the highest concentration of ZIF-8/KIT-6 (800 µg/ml). Using cheap, simple, reproducible and scalable techniques, we nano-formulated innovative bioactive nanocomposites, by incorporating the bioactive ZIF-8 (Zn2+ with imidazole), structured mesosilica and natural antioxidant compounds, curcumin or resveratrol, to generate multifunctional modalities. These eco-friendly, naturally based, safe, economical, biocompatible, and bioavailable nanocomposites are potential nanotherapeutics. The anti-blastocystosis results of these three nanocomposites indicate their potentially promising innovative and safe use as alternative Blastocystosis therapies.

PEGylated green halloysite/spinel ferrite nanocomposites for pH sensitive delivery of dexamethasone: A potential pulmonary drug delivery treatment option for COVID-19.

Dexamethasone (Dex) is used in drug regimen for treatment of Coronavirus disease (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fusion and entry into the cell occurs at pH 5.5. In our present study, we have identified a green, cheap clay based halloysite (Hal) nanoformulation with release capability of Dex at such interactive pH condition. 30%ZnFe2O4/Hal and 30%NiFe2O4/Hal were prepared by one-pot synthesis technique. Dex (5% wt/wt) was functionalized over both nanocomposites. Finally, polyethylene glycol (PEG) was coated over ZnFe2O4/Hal/Dex and NiFe2O4/Hal/Dex nanocomposite using lyophilization technique (0.08 µl/mg of nanocarrier). The release ability of Dex was studied under pulmonary infection and normal pH conditions (pH = 5.6 and 7.4). The characterization study using X-ray diffraction (XRD) and UV-visible diffuse reflectance (DRS) spectra confirmed the presence of spinel ferrites over Hal. Nitrogen adsorption isotherm showed the surface area of ZnFe2O4/Hal (75 m2/g), pore volume (0.27 cm3/g) with average pore size (14.5 nm). Scanning electron microscope/Energy dispersive spectroscopy (SEM-EDS) and Transmission electron microscopy analysis revealed a textural change in halloysite tubular type indicating drug adsorption and PEG adhesion. DRS spectra indicated an intergrowth of zinc ferrite nanoparticles on the halloysite nanotubes. Interestingly, ZnFe2O4/Hal/Dex/PEG exhibited a high Dex release ability (17.5%, 168 h) at pH = 5.6 relevant to SARS-CoV-2 fusion entry into the cell pH condition of 5.5. Comparatively, the nanocomposite showed a less Dex release (<5%) release for 168 h at neutral pH = 7.4. The drug release kinetics were studied and the obtained data were fitted for the release constant and release exponent, using the Korsmeyer-Peppas model. To test the compatibility of our nanocomposites, we performed the cell viability assay (MTT) using HEK293 cells. Our results showed that at 0.3 mg/ml, Dex-loaded nanocomposite had a statistically significant improvement in cell viability compared to Dex alone. These results suggest that our nanocomposite has prevented the toxic effect of Dex and has huge potential to act as pulmonary drug delivery system for targeted lung infection therapeutics.

Immunity, Sex Hormones, and Environmental Factors as Determinants of COVID-19 Disparity in Women.

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality and morbidity due to COVID-19 in women has also been addressed.

Impact of Poly (Styrene-Acrylic Acid) Latex Nanoparticles on Colorectal and Cervical Cancer Cells.

Polymer nanoparticles are a promising approach for cancer treatment and detection, due to their biocompatibility, biodegradability, targeting capabilities, capacity for drug loading and long blood circulation time. This study aims to evaluate the impact of poly (styrene-acrylic acid) latex particles on colorectal and cervical cancer cells for anti-tumor efficiency. Latex particles were synthesized by a surfactant-free radical emulsion polymerization process and the obtained polymer particles were characterized in terms of size, size distribution, morphology using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and electrokinetic property (i.e., zeta potential). Human colorectal and cervical cancer, and normal cell lines, were then treated with different concentrations of poly (styrene-acrylic acid) latex particles. The cell morphology changes were pointed out using an optical microscope and the nanoparticles' (NPs) cell cytotoxicity was evaluated using MTT assay. The obtained results showed that poly (styrene-acrylic acid) latex particles are effective against colorectal and cervical cancer cells if treated with an appropriate particle concentration for 48 h. In addition, it showed that normal cells are the least affected by this treatment. This indicates that these NPs are safe as a drug delivery carrier when used at a low concentration.

Role of a metastatic suppressor gene KAI1/CD82 in the diagnosis and prognosis of breast cancer.

Globally, breast cancer is the most common type of cancer in females and is one of the leading causes of cancer death in women. The advancement in the targeted therapies and the slight understanding of the molecular cascades of the disease have led to small improvement in the rate of survival of breast cancer patients. However, metastasis and resistance to the current drugs still remain as challenges in the management of breast cancer patients. Metastasis, potentially, leads to failure of the available treatment, and thereby, makes the research on metastatic suppressors a high priority. Tumor metastasis suppressors are several genes and their protein products that have the capability of arresting the metastatic process without affecting the tumor formation. The metastasis suppressors KAI1 (also known as CD82) has been found to inhibit tumor metastasis in various types of solid cancers, including breast cancer. KAI1 was identified as a metastasis suppressor that inhibits the process of metastasis by regulating several mechanisms, including cell motility and invasion, induction of cell senescence, cell-cell adhesion and apoptosis. KAI1 is a member of tetraspanin membrane protein family. It interacts with other tetraspanins, chemokines and integrins to control diverse signaling pathways, which are crucial for protein trafficking and intracellular communication. It follows that better understanding of the molecular events of such genes is needed to develop prognostic biomarkers, and to identify specific therapies for breast cancer patients. This review aims to discuss the role of KAI1/CD82 as a prognosticator in breast cancer.

Faculty readiness for online teaching at Imam Abdulrahman Bin Faisal University during the COVID-19 crisis: a cross-sectional study.

Background: The outbreak of the COVID-19 pandemic has affected the education sector around the world. In order to control the spread of the virus, eLearning practice has been introduced in Saudi higher education. Such online communication has become an important tool to narrow the teaching practice gap. This study assessed the characteristics of eLearning and distance learning and the inclination of Imam Abdulrahman BinFaisal University (IAU) faculty members in terms of skills, and managing classes and tests using online learning tools. Methods: A QuestionPro questionnaire with 22 questions on eLearning experience, training experience, and skills and knowledge in the educational process of IAU teaching faculty was conducted through the online university e-mail domain. The questionnaire was sent to the IAU's teaching faculty. The questionnaire's reliability was studied using Cronbach's a coefficient. The criterion value was statistically studied using the KMO (Kaiser-Meyer-Olkin) and Bartlett's test. The variables associated with the present survey model were analysed using Structural Equation Modelling (SEM). Results: The study showed positive responses and readiness (skills and abilities) and the effectiveness of IAU's faculty members to perform e-learning activities during COVID-19. IAU faculty received a strong positive response, and the respondents were also impressed with and agreed on trainer knowledge, session management, communication and expertise on training topics. Conclusions: The positive response indicates the readiness of IAU to provide the necessary support (tools, information and updates) required for a successful online educational process.

Emerging insights into mitochondria-specific targeting and drug delivering strategies: Recent milestones and therapeutic implications.

Mitochondria are a major intracellular organelle for drug targeting due to its functional roles in cellular metabolism and cell signaling for proliferation and cell death. Mitochondria-targeted treatment strategy could be promising to improve the therapeutic efficacy of cancer while minimizing the adverse side effects. Over the last decades, several studies have explored and focused on mitochondrial functions, which has led to the emergence of mitochondria-specific therapies. Molecules in the mitochondria are considered to be prime targets, and a wide range of molecular strategies have been designed for targeting mitochondria compared with that of the cytosol. In this review, we focused on the molecular mechanisms of mitochondria-specific ligand targeting and selective drug action strategies for targeting mitochondria, including those premised on mitochondrial targeting of signal peptides (MTS), cell-penetrating peptides (CPPs), and use of lipophilic cations. Furthermore, most research has concentrated on specific conjugation of ligands to therapeutic molecules to enhance their effectiveness. There are several variations for the ideal design and development for mitochondrial-targeted drugs, such as selecting a suitable ligand and linker targets. However, some challenges related to drug solubility and selectivity could be resolved using the nanocarrier system. Nanoparticles yield excellent advantages for targeting and transmitting therapeutic drugs, and they offer elegant platforms for mitochondria-specific drug delivery. We explain many of the advanced and proven strategies for multifunctional mitochondria-specific targets, which should contribute to achieving better anticancer therapies in a promising future.

Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen.

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.

Zeolitic imidazolate framework-8 (ZIF-8) doped TiZSM-5 and Mesoporous carbon for antibacterial characterization.

Drug resistant bacteria affects millions worldwide and remains a serious threat to health care system. The study reports the first application of hybrid nanocomposites based on zeolitic imidazolate framework-8 (ZIF-8) with MFI structured zeolite Ti-ZSM-5 (TiZ5) and mesoporous carbon (MC). The composite was designated as TiZ5/ZIF-8 and MC/ZIF-8 was studied for antibacterial activity. Bioactive components Zn2+ and 2-methyl imidazole present in ZIF-8 was found to exert significant antibacterial effect on Escherchia. coli and Staphyloccocus. No other antibiotic drugs are required. For comparative purpose, Fe-BTC MOF (BTC = 1,3,5-benzenetricarboxylate) was used as second set of nanoformulations (TiZ5/Fe-BTC and MC/Fe-BTC) but showed a lower antibacterial activity. The phase (X-ray diffraction), texture (BET surface area), coordination (DRS-UV-Vis), and morphology (TEM) was investigated. XRD showed the presence of nanosized ZIF-8 over TiZ5 and MC. Surface area calculation using N2 adsorption isotherm showed a reduction in the micropore surface area of ZIF-8 from 1148 m2/g to 224 m2/g (80%) and an increased meso surface area from 31 m2/g to 59 m2/g (90%). The mesopore pore volume increased significantly from 0.05 cm3/g to 0.12 m2/g. MC/ZIF-8 showed similar textural modifications. FT-IR spectra and DRS-UV-Vis spectra showed distinct composite formation with TiZ5, while a weak absorption of ZIF-8 observed over MC. TEM revealed the presence of nanocomposite MC/ZIF-8 and TiZ5/ZIF-8 distributed in nanosize ranging between 25 and 50 nm. TiZ5/ZIF-8 showed the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 0.5 and 1 mg/ml, respectively against E. coli. The MIC and MBC of TiZ5/ZIF-8 against S. aureus were 1 and 2 mg/ml, respectively. MC/ZIF-8 composite had second best antibacterial activity. This study shows that ZIF-8 based composite holds a great potential against E. coli and S. aureus.

Developmental lead (Pb)-induced deficits in redox and bioenergetic status of cerebellar synapses are ameliorated by ascorbate supplementation.

Neurotoxicity induced by exposure to heavy metal lead (Pb) is a concern of utmost importance particularly for countries with industrial-based economies. The developing brain is especially sensitive to exposure to even minute quantities of Pb which can alter neurodevelopmental trajectory with irreversible effects on motor, emotive-social and cognitive attributes even into later adulthood. Chemical synapses form the major pathway of inter-neuronal communications and are prime candidates for higher order brain (motor, memory and behavior) functions and determine the resistance/susceptibility for neurological disorders, including neuropsychopathologies. The synaptic pathways and mechanisms underlying Pb-mediated alterations in neuronal signaling and plasticity are not completely understood. Employing a biochemically isolated synaptosomal fraction which is enriched in synaptic terminals and synaptic mitochondria, this study aimed to analyze the alterations in bioenergetic and redox/antioxidant status of cerebellar synapses induced by developmental exposure to Pb (0.2 %). Moreover, we test the efficacy of vitamin C (ascorbate; 500 mg/kg body weight), a neuroprotective and neuromodulatory antioxidant, in mitigation of Pb-induced neuronal deficits. Our results implicate redox and bioenergetic disruptions as an underlying feature of the synaptic dysfunction observed in developmental Pb neurotoxicity, potentially contributing to consequent deficits in motor, behavioral and psychological attributes of the organisms. In addition, we establish ascorbate as a key ingredient for therapeutic approach against Pb induced neurotoxicity, particularly for early-life exposures.

A Wild Fomes fomentarius for Biomediation of One Pot Synthesis of Titanium Oxide and Silver Nanoparticles for Antibacterial and Anticancer Application.

The present study offers an alternative method for green synthesis of the formation of two types of nanoparticles (NPs). These NPs, titanium oxide and silver NPs (TiO2 and Ag NPs, respectively), were obtained from the amalgamation of intracellular extract of a wild mushroom, Fomes fomentarius, with aqueous solutions of titanium isopropoxide and silver nitrate, respectively. F. fomentarius was identified phenotypically and by 18S ribosomal RNA gene sequencing (Gene accession no: MK635351). The biosynthesis of TiO2 and Ag NPs was studied and characterized by X-ray diffraction (XRD), diffuse reflectance UV-Visible spectroscopy (DR-UV), fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and transmission electron microscope (TEM). Success was achieved in obtaining NPs of differing sizes and shapes. The antibacterial and anticancer activity of the NPs was significant with morphological damage being caused by both, although Ag NPs (10-20 nm) were found to have profound effects on bacterial and cancer cells in comparison to TiO2 NPs (100-120 nm). These metal NPs, synthesized using wild mushrooms, hold a great potential in biomedicinedue to an effective enzyme combination, which permits them to modify different chemical compounds to less toxic forms, which is required for ecofriendly and safe biomaterials.

Anticandidal and In vitro Anti-Proliferative Activity of Sonochemically synthesized Indium Tin Oxide Nanoparticles.

The present work demonstrates the synthesis, characterization and biological activities of different concentrations of tin doped indium oxide nanoparticles (Sn doped In2O3 NPs), i.e., (Sn/In = 5%, 10% and 15%). We have synthesized different size (38.11 nm, 18.46 nm and 10.21 nm) of Sn doped In2O3 NPs. by using an ultra-sonication process. The Sn doped In2O3 NPs were characterized by by x-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) which confirmed the successful doping of tin (Sn) with Indium oxide (In2O3). Anticandidal activity was performed by standard agar dilution method using Candida albicans for the study. The minimum inhibitory/fungicidal concentration (MIC/MFC) values recorded were, 8 & >8 mg/ml for pure In2O3 NPs, 4 & 8 mg/ml for 5%, 2 & 8 mg/ml for 10%, whereas 1 & >4 mg/ml for 15% Sn doped In2O3 NPs, respectively. The topographical alteration caused by Sn doped In2O3 NPs on Candida cells, was clearly observed by SEM examination. A significant enhancement in anticandidal activity was seen, when Candida cells were exposed to (Sn/In = 5%, 10% and 15%). Moreover, we have also evaluated the impact of Sn-In2O3 NPs on human colorectal carcinoma cells (HCT-116). The results demonstrated that Sn-In2O3 NPs (Sn/In = 5%, 10% and 15%), caused dose dependent decrease in the cancer cell viability as the low dosage (2.0 mg/mL) showed 62.11% cell viability, while 4.0, 8.0, 16.0, 32.0 mg/mL dosages showed 20.45%, 18.25%, 16.58%, and 15.58% cell viability. In addition, the treatment of Sn-In2O3 NPs also showed significant cellular and anatomical changes in cancer cells as examined by microscopes. We have also examined the impact of Sn-In2O3 NPs (5%, 10%, 15%) on normal cells (HEK-293) and the results demonstrate that Sn-In2O3 NPs did not reduce the cell viability of normal cells.

Using Fomitopsis pinicola for bioinspired synthesis of titanium dioxide and silver nanoparticles, targeting biomedical applications.

The current study proposes a bio-directed approach for the formation of titanium oxide and silver nanoparticles (TiO2 and Ag NPs), using a wild mushroom, Fomitopsis pinicola, identified by 18S ribosomal RNA gene sequencing (gene accession no. MK635350) and phenotypic examination. NP synthesis was confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), diffuse reflectance UV-visible spectroscopy (DR-UV), and scanning and transmission electron microscopy (SEM/TEM). Furthermore, the impact of NPs on Escherichia coli and Staphylococcus aureus and a human colon cancer cell line (HCT) were evaluated by MIC/MBC and MTT assays, respectively, along with structural morphogenesis by different microscopy methods. The results obtained showed that TiO2 and Ag NPs were found to be significantly active, however, slightly enhanced antibacterial and anticancer action was seen with Ag NPs (10-30 nm). Such NPs can be utilized to control and treat infectious diseases and colon cancer and therefore have potential in a range of biomedical applications.

Targeted therapeutic effect against the breast cancer cell line MCF-7 with a CuFe2O4/silica/cisplatin nanocomposite formulation.

The combination of magnetic nanoparticles with a porous silica is a composite that has attracted significant attention for potential multifunctional theranostic applications. In this study, 30 wt % CuFe2O4 was impregnated into a matrix of monodispersed spherical hydrophilic silica (HYPS) nanoparticles through a simple dry impregnation technique. The chemotherapy drug cisplatin was loaded through electrostatic equilibrium adsorption over 24 h in normal saline solution. The presence of cubic spinel CuFe2O4 on HYPS was confirmed through powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and diffuse reflectance UV-vis spectroscopy (DR UV-vis) analysis. The HYPS particles showed a surface area of 170 m2/g, pore size of 8.3 nm and pore volume of 0.35 cm3/g. The cisplatin/CuFe2O4/HYPS nanoformulation showed the accumulation of copper ferrite nanoparticles on the surface and in the pores of HYPS with a surface area of 45 m2/g, pore size of 16 nm and pore volume of 0.18 cm3/g. Transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) mapping analysis showed the presence of homogeneous silica particles with nanoclusters of copper ferrite distributed on the HYPS support. Vibrating sample magnetometry (VSM) analysis of CuFe2O4/HYPS showed paramagnetic behavior with a saturated magnetization value of 7.65 emu/g. DRS UV-vis analysis revealed the functionalization of cisplatin in tetrahedral and octahedral coordination in the CuFe2O4/HYPS composite. Compared to other supports such as mesocellular foam and silicalite, the release of cisplatin using the dialysis membrane technique was found to be superior when CuFe2O4/HYPS was applied as the support. An in vitro experiment was conducted to determine the potential of CuFe2O4/HYPS as an anticancer agent against the human breast cancer cell line MCF-7. The results show that the nanoparticle formulation can effectively target cancerous cells and could be an effective tumor imaging guide and drug delivery system.

SPIONs/3D SiSBA-16 based Multifunctional Nanoformulation for target specific cisplatin release in colon and cervical cancer cell lines.

Multifunctional nanomaterials can be used for dual applications: drug delivery as well as in bioimaging. In current study, we investigated potential use of silica based supports; 3D cage type SiSBA-16 (S-16), monodispersed hydrophilic spherical silica (HYPS) and mesocellular foam (MSU-F) for cisplatin (Cp) delivery. To obtain magnetic resonance characteristics, 10 wt% iron oxide was loaded through enforced adsorption technique. For pH stimuli responsive release of Cp, 10 wt%SPIONs/S-16 was functionalized with 3-(Aminopropyl)triethoxysilane (A) and poly acrylic acid (PAA) termed as 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp. By TEM analysis, the average diameter of the SPIONs was found to range between 10-60 nm. VSM analysis showed saturation magnetization over S-16, HYPS and MSU-F were in the following order: 10 wt%SPIONs/HYPS (4.08 emug-1) > 10 wt%SPIONs /S-16 (2.39 emug-1) > 10 wt%SPIONs/MSU-F (0.23 emug-1). Cp release study using dialysis membrane in PBS solution over 10 wt%SPIONs/S-16 nanoformulations showed highest cumulative release (65%) than 10 wt%SPIONs/MSU-F-A-Cp (63%), 10 wt%SPIONs/HYPS-A-Cp (58%), and Cp-F127/S-16 (53%), respectively. 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp were evaluated for in vitro target anticancer efficiency in human cancer cell lines (colon cancer (HCT 116), cervical cancer (HeLa)) and normal cells (Human embryonic kidney cells (HEK293) using MTT and DAPI staining. 10 wt%SPIONs/S-16-A-Cp treated Hela and HCT116 cancerous cell lines showed significant control of cell growth, apoptotic activity and less cytotoxic effect as compared to Cp and 10 wt%SPIONs/S-16. Target specific Cp release in the cells shows that 10 wt%SPIONs/S-16-A-Cp can be easily upgraded for magnetic resonance imaging capability.

Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance.

The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.

Cisplatin-functionalized three-dimensional magnetic SBA-16 for treating breast cancer cells (MCF-7).

The engineering of multifunctional therapeutics in an integrated single platform is demonstrated using three-dimensional SBA-16 (S-16). 10 wt% iron oxide nanoparticles (Fe) were loaded into the cage type of cubic pores through enforced adsorption technique. Fe/S-16 is then functionalized with amine-based silane (A), polyacrylic acid (P) and cisplatin (Cp). The physicochemical textural analysis showed the formation of nano metal oxide distributions at pore walls of S-16 with magnetization of 2.39 emu/g. S-16 based nanoformulations showed high percentage of Cp adsorption (90%) and percentage cumulative release (60%). in vitro study of Fe/S-16-A-Cp showed high toxicity against breast cancer cell line MCF-7 and normal cell line Human foreskin fibroblast (HFF-1) compared to Fe/S-16 indicating cisplatin profusion inside the cells than free cisplatin. While skin fibroblast seems to be resistant to Fe/S-16-AP-Cp with very high LC50 in compare to MCF-7. This indicates the unrelease of cisplatin in skin fibroblast after Fe/S-16-AP-Cp treatment due to effective encapsulation inside the cubic pores and core blockage due to pH-sensitive polyacrylic acid. Also, these treatments resulted in morphological changes in the cells such as DNA condensation and nuclear fragmentation.