Imalka Munaweera

Novel wrinkled periodic mesoporous organosilica nanoparticles for hydrophobic anticancer drug delivery

Novel wrinkled structured periodic mesoporous organosilica (PMO) nanoparticles have been developed for the hydrophobic anticancer drug delivery. The PMO materials were characterized by TEM, Raman, TGA, zetapotential and PXRD. These novel wrinkled PMOs have tunable surface area, hydrophobicity and pore sizes which are suitable for hydrophobic drug delivery. The hydrophobic anticancer drug paclitaxel was used as a model drug and the PMO shows a higher paclitaxel drug loading efficiency compared to pure mesoporous silica (MS) nanoaparticles. In vitro paclitaxel drug release studies show slow and sustained release of paclitaxel drugs from the PMO nanoparticles compared to the paclitaxel release from MS nanoparticles.

Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer

Nitric oxide (NO) and cisplatin releasing wrinkle-structured amine-modified mesoporous silica (AMS) nanoparticles have been developed for the treatment of non-small cell lung cancer (NSCLC). The AMS and NO- and cisplatin-loaded AMS materials were characterized using TEM, BET surface area, FTIR and ICP-MS, and tested in cell culture. The results show that for NSCLC cell lines (i.e., H596 and A549), the toxicity of NO- and cisplatin-loaded silica nanoparticles (NO-Si-DETA-cisplatin-AMS) is significantly higher than that of silica nanoparticles loaded with only cisplatin (Si-DETA-cisplatin-AMS). In contrast, the toxicity of NO-Si-DETA-cisplatin-AMS toward normal lung cell lines is not significantly different from that of Si-DETA-cisplatin-AMS (normal lung fibroblast cells WI-38) or is even lower than that of Si-DETA-cisplatin-AMS (normal lung epithelial cells BEAS-2B). The NO-induced sensitization of tumor cell death demonstrates that NO is a promising enhancer of platinum-based lung cancer therapy.

Electrospun cellulose acetate-garnet nanocomposite magnetic fibers for bioseparations.

Cellulose acetate fibers with magnetic properties have recently attracted much attention because of their potential novel applications in biomedicine such as for cell and protein separations, magnetic resonance imaging contrast agents, and magnetic filters. In this work, as synthesized yttrium iron garnet and gadolinium substituted yttrium iron garnet nanoparticles have been used to generate magnetic filter paper. Garnet nanoparticles dispersed in cellulose acetate polymer solutions were electrospun as free-standing nonwoven fiber mats as well as on cellulose filter paper substrates resulting in magnetic filter papers. The magnetic fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and superconducting quantum interference device (SQUID) magnetic property measurements. The resulting magnetic polymer nanocomposites can be easily picked up by an external magnet from a liquid medium. Fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) was separated from solution by using the magnetic filter paper.

Chemoradiotherapeutic wrinkled mesoporous silica nanoparticles for use in cancer therapy

Over the last decade, the development and application of nanotechnology in cancer detection, diagnosis, and therapy have been widely reported. Engineering of vehicles for the simultaneous delivery of chemo- and radiotherapeutics increases the effectiveness of the therapy and reduces the dosage of each individual drug required to produce an observable therapeutic response. We here developed a novel chemoradiotherapeutic 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid coated/uncoated platinum drug loaded, holmium-containing, wrinkled mesoporous silica nanoparticle. The materials were characterized with TEM, FTIR, 1H NMR, energy dispersive x-ray, inductively coupled plasma-mass spectrometry, and zeta potential measurements. In vitro platinum drug release from both lipid coated and uncoated chemoradiotherapeutic wrinkled mesoporous silica are reported. Various kinetic models were used to analyze the release kinetics. The radioactivity of the chemoradiotherapeutic nanocarriers was measured after neutron-activation.

Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.

Radiotherapeutic bandage based on electrospun polyacrylonitrile containing holmium-166 iron garnet nanoparticles for the treatment of skin cancer

Radiation therapy is used as a primary treatment for inoperable tumors and in patients that cannot or will not undergo surgery. Radioactive holmium-166 ((166)Ho) is a viable candidate for use against skin cancer. Nonradioactive holmium-165 ((165)Ho) iron garnet nanoparticles have been incorporated into a bandage, which, after neutron-activation to (166)Ho, can be applied to a tumor lesion. The (165)Ho iron garnet nanoparticles ((165)HoIG) were synthesized and introduced into polyacrylonitrile (PAN) polymer solutions. The polymer solutions were then electrospun to produce flexible nonwoven bandages, which are stable to neutron-activation. The fiber mats were characterized using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma mass spectrometry. The bandages are stable after neutron-activation at a thermal neutron-flux of approximately 3.5 × 10(12) neutrons/cm(2)·s for at least 4 h and 100 °C. Different amounts of radioactivity can be produced by changing the amount of the (165)HoIG nanoparticles inside the bandage and the duration of neutron-activation, which is important for different stages of skin cancer. Furthermore, the radioactive bandage can be easily manipulated to irradiate only the tumor site by cutting the bandage into specific shapes and sizes that cover the tumor prior to neutron-activation. Thus, exposure of healthy cells to high energy β-particles can be avoided. Moreover, there is no leakage of radioactive material after neutron activation, which is critical for safe handling by healthcare professionals treating skin cancer patients.

Radiotherapeutic bandage for the treatment of squamous cell carcinoma of the skin

INTRODUCTION Squamous cell carcinoma (SCC) is the second most common form of skin cancer in the United States. The efficacy of a pharmaceutically elegant radiotherapeutic bandage, previously described by us for application against SCC of the skin, was tested for the first time in vivo using a subcutaneous SCC mouse model and a therapeutically relevant radiation dose. METHODS Female athymic nude mice were injected with human Colo-16 SCC cells subcutaneously and after eight days (average tumor volume: 35±8.6mm(3)) received no treatment, or were exposed to non-radioactive or radioactive (92.5±18.5MBq) bandages for approximately 1h (n=10 per group). After treatment, tumors were measured over fifteen days, tumor volume ratios (TVRs) compared and histopathology performed. RESULTS Fifteen days after treatment, the TVR of the radioactive bandage treatment group was 3.3±4.5, while TVRs of the non-radioactive bandage treatment and no treatment control groups were 33.2±14.7 and 26.9±12.6, respectively. At the time of necropsy, there was mild focal epidermal hyperplasia surrounding a small area of epidermal ulceration in the radioactive bandage group. No other examined tissue (i.e., muscle, liver, kidney, lung, spleen and heart) showed significant lesions. CONCLUSIONS Our radiotherapeutic bandage exhibits promising efficacy against SCC of the skin in a mouse model. It can be individually tailored for easy application on tumor lesions of all shapes and sizes, and could complement or possibly replace surgery in the clinic.