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

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.

Keywords

• silver nanoparticle
• somatostatin receptor
• active targeting
• octreotide
• in vivo lung cancer delivery
• molecular modeling
• receptor binding