Chemopreventive role of Tin oxide-Chitosan-Polyethylene glycol-Crocin nanocomposites against Lung cancer: An in vitro and in vivo approach

Highlights

• Lung cancer (LC) is a major cause of cancer-associated mortalities worldwide.

• Nano-formulations has aroused as a talented tool for cancer treatment.

• Chitosan micelles was being emerged in the field of drug delivery.

• The SCP-Cr-NCs has reduced the tumor weight and inflammatory markers in the LC mice.

Abstract

Background

Lung cancer (LC) is a foremost cause of cancer-associated mortalities worldwide and it causes 17 % of the total cancer incidences and 20 % of the cancer-associated mortalities annually.

Objective

In this exploration, we intended to formulate the Tin oxide-Chitosan-Polyethylene glycol-Crocin nanocomposites (SCP-Cr-NCs) and examine its anticancer role against the LC in both in vitro and in vivo models.

Methodology

The formulated SCP-Cr-NCs were characterized using several methods. The LC was initiated to the BALB/c mice via injecting the 2 × 10⁶ of A549 cells into the posterior flank and treated with the 10 and 20 µM of formulated SCP-Cr-NCs for 19 days. The tumor weight and xenobiotic dysfunction markers status was examined by standard methods. The status of pro-inflammatory markers was studied using ELISA kits. The lung histology was examined microscopically. The viability of SCP-Cr-NCs treated A549 cells were investigated. The ROS and MMP status and apoptosis in the SCP-Cr-NCs treated A549 cells were inspected by fluorescence staining techniques.

Results

The tumor weight and the status of xenobiotic dysfunction markers were remarkably reduced by the SCP-Cr-NCs. The SCP-Cr-NCs supplementation also diminished the IL-1β, TNF-α, IL-6, and CEA. The viability of SCP-Cr-NCs administered A549 cells were reduced drastically. The outcomes of fluorescence assay was demonstrated that the SCP-Cr-NCs were diminished the MMP and elevated the ROS status and apoptosis in the A549 cells. SCP-Cr-NCs also restrained the cell adhesion of A549 cells.

Conclusion

Collectively, our findings provided the evidence that the formulated SCP-Cr-NCs demonstrated the anticancer potential and it could be a talented chemopreventive candidate to treat the LC.

Introduction

Lung cancer (LC) is a major cause of cancer-associated mortalities around the world [1]. LC contributes for nearly 17 % of the cancer incidences and 20 % of the cancer-associated mortalities annually worldwide [2]. LC can be classified into two types as non-small cell LC (NSCLC) and small cell LC (SCLC) based on the pathological features [3]. NSCLC contributes nearly 80 % of all LCs, whereas SCLC contributes only for 20 % [4]. The extremely poor prognosis of LC is primarily due to the characteristics of distant organ metastasis, high degree genetic and cellular diversity, and rapid progress and metastasis [5], [6]. LC was renowned as a major type of cancers and demonstrates the strong association with inflammation [7], [8]. There are huge resemblances in signaling, cellular behaviors and gene expression shared by inflammation and cancer. Both mechanisms are involved improved cell migration and the penetrated inflammatory cells generate diverse chemokines and cytokines to enhance the invasion of tumor cells to inflammation-regulated metastasis [9].

The administration of chemotherapeutic drugs is the first-line treatment or the NSCLC [10]. Though, many patients with advanced state of NSCLC moderately response to these treatments with less than 35 % response rate and it even lower for the second-line treatments [11], [12]. Moreover, the adverse effects linked with chemotherapeutic drugs reduce the application of these drugs. Therefore, the exploration of novel approaches for the NSCLC treatment is required. The survival rates of cancer patients are elevated notably over the past decades, but the victims in the later stages are still struggling to attain an operative treatments [13]. The existing cancer therapies have unprotected the nearby healthy cells to a diverse unwanted risks. Therefore researchers attempting to shift their attention to safer and potential formulation as they have potential to mediate a various cellular events like growth, metastasis, and apoptosis [14].

Nano-formulations has emerged as a talented tool for cancer treatment due to its gene silencing and targeted drug delivery properties in cancer cells. Besides, they also were utilized as a diagnostic tool for different cancers [15]. The advancements in the materials science have donated to nanoparticle-based therapeutic options and becoming a hopeful therapeutic strategy [16]. Nano-formulations demonstrate a hopeful option to attain improved bioavailability and targeted delivery of free drugs [17]. Nanomaterials contributing a major role in the novel biomedical researches, and in diverse fields of science and technology [18].

Chitosan is a derivative of chitin and talented natural polysaccharide, which is extensively utilized due to its easy degradation and biocompatibility without toxicities [19]. Chitosan based polymeric micelles was being emerged for the enhancement of bioavailability of many drugs and minimizing their toxicities [20], [21], [22]. Titanium dioxide (TiO₂) is naturally available oxide with wide surface area and utilized as a good material in health and medical usages because of its inert property [23], [24]. Both TiO₂ and chitosan are inert, biocompatible and chemically stable hence they could be supportive in the formulation of nano-carriers for the drug delivery and other purposes. Crocin is a bioactive compound of plant Crocus sativus L. [25]. Crocin demonstrated the excellent bioactivities experimentally like anti-nociceptive [26], neuroprotective [27], [28], nephron-protective [29], hepato-protective [30], and cardio-protective [31] activities. The current study was focused to formulate the Tin oxide-Chitosan-Polyethylene glycol-Crocin nanocomposites (SCP-Cr-NCs) and evaluate its therapeutic roles against the NSCLC in both in vitro and in vivo models.