Tumor-targeted and pH-controlled delivery of doxorubicin using gold nanorods for lung cancer therapy

Narsireddy Amreddy,1,2 Ranganayaki Muralidharan,1,2 Anish Babu,1,2 Meghna Mehta,2,3 Elyse V Johnson,4 Yan D Zhao,2,5 Anupama Munshi,2,3 Rajagopal Ramesh1,2,6 1Department of Pathology, 2Stephenson Cancer Center, 3Department of Radiation Oncology University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 4CytoViva Inc., Auburn, AL, USA; 5Department of Biostatistics and Epidemiology, 6Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: In lung cancer, the efficacy of conventional chemotherapy is limited due to poor drug accumulation in tumors and nonspecific cytotoxicity. Resolving these issues will increase therapeutic efficacy.Methods: GNR-Dox-Tf-NPs (gold nanorod-doxorubicin-transferrin-nanoparticles) were prepared by different chemical approaches. The efficacy of these nanoparticles was carried out by cell viability in lung cancer and primary coronary artery smooth muscle cells. The receptor-mediated endocytosis studies were done with human transferrin and desferrioxamine preincubation. The GNR-Dox-Tf nanoparticles induced apoptosis, and DNA damage studies were done by Western blot, H2AX foci, and comet assay.Results: We developed and tested a gold nanorod-based multifunctional nanoparticle system (GNR-Dox-Tf-NP) that carries Dox conjugated to a pH-sensitive linker and is targeted to the transferrin receptor overexpressed in human lung cancer (A549, HCC827) cells. GNR-Dox-Tf-NP underwent physicochemical characterization, specificity assays, tumor uptake studies, and hyperspectral imaging. Biological studies demonstrated that transferrin receptor-mediated uptake of the GNR-Dox-Tf-NP by A549 and HCC827 cells produced increased DNA damage, apoptosis, and cell killing compared with nontargeted GNR-Dox-NP. GNR-Dox-Tf-NP-mediated cytotoxicity was greater (48% A549, 46% HCC827) than GNR-Dox-NP-mediated cytotoxicity (36% A549, 39% HCC827). Further, GNR-Dox-Tf-NP markedly reduced cytotoxicity in normal human coronary artery smooth muscle cells compared with free Dox.Conclusion: Thus, GNR-Dox-Tf nanoparticles can selectively target and deliver Dox to lung tumor cells and alleviate free Dox-mediated toxicity to normal cells. Keywords: doxorubicin, gold, lung cancer, nanoparticles, transferrin, tumor targetin

Emerging Nanotechnology in Chronic Respiratory Diseases

A large population, including people of all age groups, is suffering from chronic respiratory diseases worldwide. Asthma, chronic obstructive pulmonary disease, occupational lung diseases, cystic fibrosis, etc. are the most common of these diseases and are noncurable with conventional and currently available therapies. Nanotechnology is emerging as a great therapeutic promise in different spheres including drug delivery systems and is becoming the technology of choice nowadays. The administration of drugs via inhalation helps in avoiding the first-pass metabolism by targeted delivery to the affected site. It has been observed that there is a huge diversity in nanotechnology being used in pulmonary diseases, and thus safety assessment is a challenging as well as important task. The present review focuses on some of the major emerging nanotechnologies for chronic pulmonary diseases and includes some of the latest studies in the field of nanomedicines

Prerequisite of a Holistic Blend of Traditional and Modern Approaches of Cancer Management

Background: With the advent of changes in lifestyle of people all around the world, cancer cases have been showing an exponential rise. Researchers from varied fields have been trying to solve this tricky issue. Methods: We undertook a systematic search of bibliographic databases of peer-reviewed research literature to evaluate the holistic blend of modern and traditional approaches, especially the Ayurvedic perspective of treatment of cancer along with the effect of our diet and lifestyle on the management (both prevention and cure) of cancer. Results: On the basis of extensive literature survey, it was found that Ayurveda as one of the ancient medicinal systems had been very well documented for utilizing its best practices for the treatment of various diseases including cancer, by utilization of several herbal plants and dietary interventions as therapeutics. Active components present in various herbs, which interfere with certain molecular targets to inhibit carcinogenesis are also summarized. Further, beneficial effects of yoga and exercise on psychological distress, cancer-related fatigue and global side-effects as well as their mechanism of action are also discussed. In addition, we recapitulate an upcoming field of Ayurgenomics to understand the possible correlation of Prakriti with genetics as well as epigenetics. Conclusion: Both genetic as well as environmental factors have shown their linkage with cancer. Substantial advancements in the field of targeted therapies have opened new horizons for the cancer patients. To fight with this grave situation, a combination of ancient and modern medicinal systems seems to be the need of the hour