Octreotide-conjugated silver nanoparticles for active targeting of somatostatin receptors and their application in a nebulized rat model

Ahmed A H Abdellatif,Abdulmajeed Alqasoumi,Riaz A Khan,Ahmad H Alhowail,Mansour Alsharidah,Ayman M Mousa,Ahmed M Mohammed,Osamah Al Rugaie,Sultan M Sajid

doi:10.1515/ntrev-2022-0021

Ahmed A H Abdellatif, Abdulmajeed Alqasoumi + Show 7 more

Open Access

https://doi.org/10.1515/ntrev-2022-0021

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Abstract

Abstract Drug uptake and distribution through cell–receptor interactions are of prime interest in reducing the adverse effects and increasing the therapeutic effectiveness of delivered formulations. This study aimed to formulate silver nanoparticles (AgNPs) conjugated to somatostatin analogs for specific delivery through somatostatin receptors (SSTRs) expressed on cells and by nebulizing the prepared AgNPs formulations into lung cells for in vivo application. AgNPs were prepared using the citrate reduction method, yielding AgNPs–CTT, which was further chemically conjugated to octreotide (OCT) to form AgNPs–OCT through an amide linkage. The AgNPs–OCT formulation was coated using alginate to yield a carrier, AgNPs–OCT–Alg, feasible for drug delivery through nebulization. AgNPs were uniform in size with an acceptable range of zeta potential. Furthermore, the concentrations of AgNP formulations were found safe for the model cell lines used, and cell proliferation was significantly reduced in a dose-dependent manner (p < 0.05). In the healthy lung tissues, AgNPs–OCT–Alg accumulated at a concentration of 0.416 ± 5.7 mg/kgtissue, as determined via inductively coupled plasma optical emission spectrometry. This study established the accumulation of AgNPs, specifically the AgNPs–OCT–Alg, in lung tissues, and substantiated the active, specific, and selective targeting of SSTRs at pulmonary sites. The anticancer efficacy of the formulations was in vitro tested and confirmed in the MCF-7 cell lines. Owing to the delivery suitability and cytotoxic effects of the AgNPs–OCT–Alg formulation, it is a potential drug delivery formulation for lung cancer therapy in the future.

Highlights

It is difficult to diagnose lung cancer because it has no early observable symptoms
The yield% was calculated for Ag0 synthesized in the AgNPs–CTT, AgNPs–OCT, AgNPs–OCT–Alg to be 2.82 ± 0.016 mg/100 mL (≈ 77.9%), 2.43 ± 0.21 mg/100 mL (≈ 67.12%), and 2.166 ± 0.19 mg/100 mL (≈ 59.83%), respectively
In the model cytotoxicity evaluation experiment involving the Michigan Cancer Foundation-7 (MCF-7) cell lines, the results showed that treatment of the breast cancer cell lines with AgNPs–CTT, AgNPs–OCT, and AgNPs–OCT–Alg significantly reduced cell proliferation in a concentrationdependent manner (Figure 4)

Summary

Introduction

It is difficult to diagnose lung cancer because it has no early observable symptoms. the tumor is typically advanced at the time of primary diagnosis and continues to progress [1,2]. The inhalation route of drug delivery is considered an effective strategy for the treatment of lung diseases [5] This route of drug administration shows favorable advantages in targeted organs such as the lungs because the drug can reach the sites directly through inhalation, provided that the carrier-based formulation and the drug to be delivered are feasible for inhalation. The direct delivery of the drug to the lungs has the advantage of lowering the required dose of the drug, which would otherwise have been higher and required more frequent administrations It targets cancer sites and reduces the toxic effects on normal/noncancerous lung cells, which is feasible [6]

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