Liquid crystalline assembly for potential combinatorial chemo–herbal drug delivery to lung cancer cells

Abstract

BackgroundLung cancer is the most common cancer and the leading cause of total deaths worldwide. Its classified into two major types including non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) based on the origin of abnormal lung cells as well as the smoking status of the patient. NSCLC is the most common and aggressive type of lung cancer representing 80%–85% of all cases.PurposeThe aim of the study was to present lyotropic liquid crystalline nanoparticles (LCNPs) as promising carriers for co-delivery of the chemotherapeutic agent, pemetrexed (PMX) and the herbal drug, resveratrol (RSV) for effective lung cancer management.MethodsThe proposed PMX-RSV-LCNPs were prepared by hydrotrope method. Hydrophobic ion pairing with cetyl trimethyl ammonium bromide (CTAB) was implemented to increase the encapsulation efficiency of the hydrophilic PMX up to 95%±3.01%.ResultsThe tailored PMX-RSV-LCNPs exhibited a particle size of 173±0.26 nm and biphasic release pattern with a relatively initial burst release within first 3–4 hour followed by sustained release up to 24 hours. Moreover, PMX-RSV-LCNPs manifested superior concentration and time dependent cytotoxicity profile against A549 lung cancer cells with IC50 4.0628 µg/mL. Besides, the enhanced cellular uptake profile based on bioadhesive properties of glyceryl monoolein (GMO) as well as energy independent (cholesterol dependent) pattern. In-vivo evaluations against urethane induced lung cancer bearing mice demonstrated the potentiality of PMX-RSV-LCNPs in tumor growth inhibition via inhibition of angiogenesis and induction of apoptosis. The results were supported by histopathological analysis and immunohistochemical Ki67 staining. Moreover, PMX-RSV-LCNPs displayed a promising safety profile via attenuating nephro- and hepatotoxicity.ConclusionPMX-RSV-LCNPs elaborated in the current study hold a great promise for lung cancer treatment.

Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex

“…[70][71][72][73][74][75][76][77][78] SAXS analysis and cryo-TEM imaging are powerful and indispensable methods for the structural characterization of the selfassembled nanostructures and nanocarriers. [79][80][81][82][83][84][85] The purpose of the present work is to investigate the selfassembly behaviour of novel amphiphilic peptides (pHK-pKV and Pal-pHK-pKV) and the cancer cell mitochondria-specific targeting by the nano-assemblies derived from the N-terminus of the HK-II protein (pHK) ( Table 1). Structural analysis of the supramolecular peptide assemblies is performed by synchrotron BioSAXS, cryo-TEM and circular dichroism spectroscopy experiments.…”

Berries polyphenols: Nano-delivery systems to improve their potential in cancer therapy

“…Average tumor weight in PMX-RSV-LCNPs-treated animals (260 ± 15 mg) was significantly lower compared to animals treated with free PMX/RSV mixture (380 ± 10 mg) and control group (605 ± 25 mg). Furthermore, PMX-RVS-LC NPs showed less nephroand hepatotoxicity, as well as a better survival rate (2 fold vs RSV/PMX mixture) [51].…”

“…However, its therapeutic applications are hindered by its low solubility [29,30], extremely light sensitivity [16,29,44], low chemical stability [16], high rate of absorption and rapid clearance from the circulation [29,44], which limits its bioavailability [16]. As for other phytochemicals, the use of nano-delivery systems has been demonstrated to be a valid strategy to overcome these limitations and increase its antitumor potential in many types of cancer, including breast [46], colon [47,48], prostate [49], skin [44,50] and lung [51] cancer.…”

Clinical Pharmacists in Chronic Care

“…The overall economic impact of lung cancer in Europe is substantial, it was found more than €100 billion, when costs related to disability and premature mortality are considered as well [400]. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 80%-85% of all cases [401,402]. More than half of the NSCLC cases are diagnosed at an advanced stage (stages III and IV) [403,404].…”