Site-Specific 111In-Radiolabeling of Dual-PEGylated Porous Silicon Nanoparticles and Their In Vivo Evaluation in Murine 4T1 Breast Cancer Model.

Dave Lumen,Surachet Imlimthan,Wujun Xu,Anu J Airaksinen,Simo Näkki,Vesa-Pekka Lehto,Mirkka Sarparanta,Elisavet Lambidis

doi:10.3390/pharmaceutics11120686

Abstract

Polyethylene glycol (PEG) has been successfully used for improving circulation time of several nanomaterials but prolonging the circulation of porous silicon nanoparticles (PSi NPs) has remained challenging. Here, we report a site specific radiolabeling of dual-PEGylated thermally oxidized porous silicon (DPEG-TOPSi) NPs and investigation of influence of the PEGylation on blood circulation time of TOPSi NPs. Trans-cyclooctene conjugated DPEG-TOPSi NPs were radiolabeled through a click reaction with [111In]In-DOTA-PEG4-tetrazine (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and the particle behavior was evaluated in vivo in Balb/c mice bearing 4T1 murine breast cancer allografts. The dual-PEGylation significantly prolonged circulation of [111In]In-DPEG-TOPSi particles when compared to non-PEGylated control particles, yielding 10.8 ± 1.7% of the injected activity/g in blood at 15 min for [111In]In-DPEG-TOPSi NPs. The improved circulation time will be beneficial for the accumulation of targeted DPEG-TOPSi to tumors.

Highlights

Several different types of nanomaterials have been investigated as carriers for targeted delivery of therapeutic and diagnostic agents in cancer [1]
In order to improve the stealth properties of porous silicon nanoparticles (PSi NPs), we decided to employ a dual-PEGylation strategy, aiming to enhance masking of the surface against immunorecognition
In the spectrum of DPEG-TOPSi, the 1355 cm−1 and 1460 cm−1 emerges from the –CH3 and –CH2 bendings, respectively

Summary

Introduction

Several different types of nanomaterials have been investigated as carriers for targeted delivery of therapeutic and diagnostic agents in cancer [1]. The surface of the nanocarrier is functionalized with affinity ligands such as tumor receptor binding peptides or antibody fragments [2]. For efficient recognition and retention, the carrier needs to exhibit sufficient circulation time to enable the targeting ligand to interact with the tumor cells. The human body has efficient clearance mechanisms which influence the circulation time of nanoparticles (NPs) and can still make the targeted delivery with nanocarriers a challenge. The circulation time has been found to be affected by several factors, such as size, morphology, and surface chemistry of the carrier. Spherical and discoidal shape has been found to be preferable and engineered surface coating can further improve the residence time in circulation. The surface coating affects circulation time by delaying and preventing the opsonization process [4,5,6]

Objectives

Methods

Results