Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy

Abstract

Late-stage diagnosis of lung cancer occurs ~95% of the time due to late manifestation of its symptoms, necessitating rigorous treatment following diagnosis. Existing treatment methods are limited by lack of specificity, systemic toxicity, temporary remission, and radio-resistance in lung cancer cells. In this research, we have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-co-glycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat lung cancers. The formulation provided controlled releases of the encapsulated therapeutic compounds, NU7441 - a potent radiosensitizer, and gemcitabine - an FDA approved chemotherapeutic drug for lung cancer chemo-radiotherapy. The MDNPs showed biphasic NU7441 release and pH-dependent release of gemcitabine. These nanoparticles also demonstrated good stability, excellent hemocompatibility, outstanding in vitro cytocompatibility with alveolar Type I cells, and dose-dependent caveolae-mediated in vitro uptake by lung cancer cells. In addition, they could be encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles and visualized by MRI in vivo. Preliminary in vivo results demonstrated the low toxicity of these particles and their use in chemo-radiotherapy to effectively reduce lung tumors. These results indicate that MDNPs can potentially be used as nano-vehicles to provide simultaneous chemotherapy and radiation sensitization for lung cancer treatment.

Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases

“…Histopathology of tissues from animals treated with nondrug loaded MDNPs showed no signs of toxicity, highlighting again the safety of the carrier. Altogether, these results highlight the synergistic effect of combined chemotherapy and radiation for lung cancer treatment alongside improved localization through the addition of a targeting moiety on the MDNP surface (Menon et al, ).…”

Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles

“…Gold NPs have been examined for imaging and radiotherapy of Tu-2449 brain tumor model in mice, [1] while nanocomposite containing poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and polylactic-co-glycolic acid core have been tested as drug carriers for the treatment of H460 lung tumor model in mice. [2] However, owing to reports on the adverse effects of NPs on the environment and human health, their potential toxicity has become a public concern. [3,4] It was recently reported that silica, gold, and titanium dioxide NPs could accelerate the migration of breast cancer cells in animal models and promote their invasion into the blood circulation by inducing endothelial leakiness.…”

Effects of multiple injections on the efficacy and cytotoxicity of folate-targeted magnetite nanoparticles as theranostic agents for MRI detection and magnetic hyperthermia therapy of tumor cells

“…In recent years, magnetic nanoparticles (MNPs) have attracted considerable attention due to their potential application in the pharmaceutical and medicine fields such as magnetic hyperthermia therapy (MHT) 1,2 , drug delivery systems [3][4][5] , magnetic resonance imaging (MRI) 6,7 , gene therapy 8 , cell labeling 9 , and immunoassay 10 .…”