Nanoemulsion Co-Loaded with XIAP siRNA and Gambogic Acid for Inhalation Therapy of Lung Cancer

Abstract

Lung cancer is a leading cause of cancer mortality worldwide, with a 5-year survival rate of less than 20%. Gambogic acid (GA) is a naturally occurring and potent anticancer agent that destroys tumor cells through multiple mechanisms. According to the literature, one of the most potent inhibitors of caspases and apoptosis currently known is the X-linked Inhibitor of Apoptosis Protein (XIAP). It is highly expressed in various malignancies but has little or no expression in normal cells, making it an attractive target for cancer treatment. Here we report the development of a chitosan (CS)-based cationic nanoemulsion-based pulmonary delivery (p.d.) system for the co-delivery of antineoplastic drugs (GA) and anti-XIAP small interfering RNA (siRNA). The results showed that the chitosan-modified cationic nanoemulsions could effectively encapsulate gambogic acid as well as protect siRNA against degradation. The apoptosis analysis confirmed that the cationic nanoemulsions could induce more apoptosis in the A549 cell line. In addition, most drugs and siRNAs have a long residence time in the lungs through pulmonary delivery and show greater therapeutic effects compared to systemic administration. In summary, this work demonstrates the applicability of cationic nanoemulsions for combined cancer therapy and as a promising approach for the treatment of lung cancer.

Surface Functionalised Parenteral Nanoemulsions for Active and Homotypic Targeting to Melanoma

“…In order to perform uptake studies in B16-F10 melanoma cells, IL, either blank or surface modified i.e., IL ST-MBS TRF, IL ST-PEG-MBS TRF, and IL B-16-F10 CMF were labelled with 0.1 mg/mL 6-coumarin (6-CUM) fluorescent probe [ 11 , 20 , 32 , 33 , 34 , 35 ]. To this aim 50 μL of a 2 mg/mL stock solution of 6-CUM in DMSO were added to 1 mL of nanoemulsion, followed by mixing with a micropipette.…”

A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review)

“…At present, beyond their application in the delivery of chemotherapeutic agents such as erlotinib, docetaxel, curcumin and quercetin, NEs are also under development for RNA delivery systems ( 57 - 60 ). Xu et al ( 61 ) reported a cationic NE delivery system based on chitosan (CS), capable of encapsulating both the antitumor drug gambogic acid and anti-X-linked inhibitor of apoptosis protein siRNA. NEs, through efficient enhancement of gambogic acid solubility, and the CS-siRNA complexation via electrostatic interactions, achieve improved siRNA protection and rapid drug release upon intracellular entry through a pH-responsive proton sponge effect, facilitating enhanced therapeutic efficacy.…”

An updated landscape on nanotechnology-based drug delivery, immunotherapy, vaccinations, imaging, and biomarker detections for cancers: recent trends and future directions with clinical success

“…However, this study was performed in vitro only further evaluation in the animal model is necessary to confirm the efficacy and stability [ 115 ]. The chitosan-modified cationic nanoemulsions were prepared which are composed of gambogic acid (GA), a naturally occurring anticancer agent, and siRNA which are targeted against X-linked Inhibitor of Apoptosis Protein (XIAP) which are potent inhibitors of caspases/apoptosis [ 116 ]. Generally, most drugs/siRNAs have a long residence time in the lungs because of pulmonary delivery thereby having greater therapeutic effects compared to systemic administration.…”