68 Ga-labeled, imatinib encapsulated, theranostic liposomes: Formulation, characterization, and in vitro evaluation of anticancer activity.

Cancer is still a global health problem. Among cancer types, breast cancer is the most frequently diagnosed one, and it causes a high mortality rate if not diagnosed in the early stages. In our study, imatinib encapsulated, nanosized, neutral/cationic liposome formulations were prepared as theranostic agents for breast cancer. After the characterization studies in which all liposomes exhibited proper profile owing to their particle size between 133 and 250 nm, polydispersity index values lower than 0.4, neutral and cationic zeta potential values, and high drug encapsulation efficiency, controlled drug release behaviors with zero-order kinetic were obtained. The higher than 90% radiolabeling efficiency values were obtained thanks to the determination of optimum radiolabeling condition (80°C temperature, 5 mCi radioactivity, and 10 min incubation period). According to the resazurin assay evaluating the cytotoxic profile of liposomes on MCF7 cells, neutral empty liposome was found as biocompatible, while both cationic liposomes (empty and drug-loaded ones) exhibited high nonspecific cytotoxicity at even low drug concentration due to the existence of stearyl amine in the formulations. However, dose-dependent cytotoxic effect and the highest cellular binding capacity were obtained by imatinib loaded neutral liposomes. In conclusion, 68 Ga-radiolabeled, imatinib-loaded, neutral, nanosized liposome formulation is the most promising one as a theranostic agent among all formulations.

99mTc-Labeled, Colistin Encapsulated, Theranostic Liposomes for Pseudomonas aeruginosa Infection.

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with 99mTc, colistin encapsulated, neutral and cationic liposome formulations were prepared as the theranostic agent for Pseudomonas aeruginosa infections. Liposomes exhibited appropriate physicochemical properties thanks to their nano-particle size (between 173 and 217 nm), neutral zeta potential value (about - 6.5 and 2.8 mV), as well as encapsulation efficiency of about 75%. All liposome formulations were radiolabeled with over 90% efficiency, and the concentration of stannous chloride was found as 1 mg.mL-1 to obtain maximum radiolabeling efficiency. In alamar blue analysis, neutral liposome formulations were found more biocompatible compared with the cationic formulations. Neutral colistin encapsulated liposomes were found to be more effective against P. aeruginosa strain according to their time-dependent antibacterial effect, in addition to their highest bacterial binding capacity. As conclusion, theranostic, nanosized, colistin encapsulated, neutral liposome formulations were found as promising agents for the imaging and treating of P. aeruginosa infections.

Radiolabeled Trastuzumab Solid Lipid Nanoparticles for Breast Cancer Cell: in Vitro and in Vivo Studies.

Radiolabeled trastuzumab (TRZ) loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m (99mTc radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles.

Radiolabeled Tedizolid Phosphate Liposomes for Topical Application: Design, Characterization, and Evaluation of Cellular Binding Capacity.

Nowadays, the incidence of acute bacterial skin and skin structure infection (ABSSSI) is increasing. The increased bioavailability and reduced drug resistance of antibiotics are crucial to obtain a more effective treatment response in these infections. These favorable properties could be achieved by different drug delivery systems such as liposomes. In this study, nanosized, radiolabeled tedizolid phosphate liposomal formulations were prepared and evaluated with their in vitro cellular binding capacity and biocompatible profile for topical treatment of ABSSSI. Liposomes were characterized by evaluation of their visual inspection, particle size (about 190-270 nm), zeta potential value (around 0), and encapsulation efficiency (nearly 10%). The release rate of tedizolid phosphate from liposomes was also studied using dialysis membranes and evaluated kinetically. The stability of formulations was observed at three different temperatures and humidity conditions for 28 days. Afterward, liposomes were labeled with 99mTc, and the optimal amount of reducing agent (stannous chloride) was determined as 500 µg in this direct labeling procedure. All liposome formulations were successfully radiolabeled with high efficiency and exhibited high radiochemical purity (> 80%) during 6 h in different media. Furthermore, the cellular bindings of liposomal formulations were evaluated in human skin fibroblast cells by measuring the radioactivity. Higher radioactivity values were obtained in CCD-1070Sk cells incubated by liposome formulations compared to sodium pertechnetate. This finding suggested that liposomal formulation increased the cellular binding of radioactivity. By the result of our study, nanosized, tedizolid phosphate encapsulated liposome formulation was found to be a favorable carrier system in the treatment of ABSSSI.

Diagnostic and therapeutic evaluation of folate-targeted paclitaxel and vinorelbine encapsulating theranostic liposomes for non-small cell lung cancer.

NSCLC is the most common type of lung cancer. However, non-specific contrast agents, radiopharmaceuticals, and treatment methods are insufficient in early diagnosis and eradication of all tumor tissue. Therefore, the formulation of a novel, targeted, specific theranostic agents possess critical importance. In our previous study, paclitaxel and vinorelbine encapsulating, Tc-99m radiolabeled, folate targeted, nanosized liposomes were formulated and found promising due to characterization properties, high cellular uptake, and cytotoxicity. In this study, in vivo therapeutic and diagnostic efficacy of liposomal formulations were tested by biodistribution study, evaluation of tumor growth inhibition, and histopathologic examination after in vitro assays on LLC1 cells. Both actively and passively targeted liposomal formulations exhibited high cellular uptake, and co-drug encapsulating liposomes showed a greater cytotoxicity profiles than free drug combination in LLC1 cells. By the results of biodistribution studies performed in NSCLC tumor-bearing C57BL/6 mice, the uptake of radiolabeled, actively folate targeted, co-drug encapsulating liposomal formulation was found to be higher in tumor tissue when compared to non-actively targeted one. Also, more effective treatment was achieved by using folate-targeted, co-drug encapsulating liposomal formulation when compared to free drugs combination according to changes in tumor size of mice. Furthermore, liposomal formulations showed lower toxicity compared to free drug combinations in the toxicity study considering body weight. Moreover, according to the histopathological study, folate targeted, co-drug encapsulating liposomes not only inhibited the tumor growth effectively but also restricted the lung metastasis entirely.

Targeted Alpha Therapy and Nanocarrier Approach.

The rates of cancer incidence and mortality are increasing day by day. Although several conventional methods including surgery, chemotherapy, and radiotherapy (RT) exist for cancer treatment, they are insufficient in the eradication of all tumor tissues and have some side-effects such as narrow therapeutic index and serious side-effects to healthy tissues. Moreover, it may probably recur in time due to the survival and spreading of cancerous cells or any possible metastases. Targeted radionuclide therapy is a promising alternative. α particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon emission of α particles, the daughter nuclides induce a recoil energy to lead decoupling from any chemical bond that may accumulate in normal tissues. Targeted α therapy can also be performed by targeted delivery systems apart from mAb, mAb fragments, peptides, and small molecules for selective tumor therapy. Targeted drug delivery systems have been developed to overcome the limitations of α therapy. Moreover, drug delivery systems are one of the most searched applications in cancer imaging and/or treatment due to their targeting ability to tumor or biocompatibility properties. The aim of this article is to summarize tumor therapy applications, targeted α RT approach, and to review the role of drug delivery systems in the delivery of α particles for cancer therapy and some instances of targeted α-emitting drug delivery systems from the literature.

Clinical Applications of Nanosized Drug-Delivery Systems in Lung Cancer Imaging and Therapy.

Globally, lung cancer is one of the most frequently diagnosed and deadliest types of cancer. Lung cancer imaging can be performed using both invasive and noninvasive techniques, including magnetic resonance, positron emission tomography, single photon emission computed tomography, chest radiography, and computed tomography. But nonspecific contrast agents and radiopharmaceuticals are insufficient for early and specific diagnoses and imaging. In the case of lung cancer therapy, conventional therapeutic agents and radiotherapy may cause severe and systemic adverse and toxic effects and fail to eradicate all tumor tissue. Therefore, formulation of novel, targeted, and specific agents is critically important to overcome these challenges. In this review, we summarize lung cancer classification, current methods for lung cancer imaging and therapy, and future options containing nanosized systems for lung cancer imaging and/or therapy.

Current and Future Approaches for Effective Cancer Imaging and Treatment.

Cancer poses a major health problem, not only due to cancer-related deaths but also because of treatment toxicities. This review discusses early diagnosis and strategies to overcome treatment difficulties, to facilitate recovery, and prevent deaths. Generally, noninvasive techniques such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission computed tomography (PET), and their hybrid systems, including SPECT/CT, PET/CT, and PET/MRI, are used in diagnosis of cancer. Cancer treatment in clinics still comprises conventional methods such as chemotherapy, radiotherapy, and surgery. However, these techniques and methods are often inadequate. Therefore, new approaches, including the formulation of actively and/or passively targeted nanosized drug delivery systems and combined treatment protocols, are being investigated. In this article, conventional cancer imaging and treatment are reviewed. In addition, the formulation of nanosized systems and their use in cancer treatment are discussed and combined diagnostic and therapeutic (theranostic) approach are proposed as additional cancer therapies.