Abstract
BackgroundThe delivery of plasmonic particles, such as gold nanorods, to the tumor microenvironment has attracted much interest in biomedical optics for topical applications as the photoacoustic imaging and photothermal ablation of cancer. However, the systemic injection of free particles still crashes into a complexity of biological barriers, such as the reticuloendothelial system, that prevent their efficient biodistribution. In this context, the notion to exploit the inherent features of tumor-tropic cells for the creation of a Trojan horse is emerging as a plausible alternative.ResultsWe report on a convenient approach to load cationic gold nanorods into murine macrophages that exhibit chemotactic sensitivity to track gradients of inflammatory stimuli. In particular, we compare a new model of poly-l-lysine-coated particles against two alternatives of cationic moieties that we have presented elsewhere, i.e. a small quaternary ammonium compound and an arginine-rich cell-penetrating peptide. Murine macrophages that are exposed to poly-l-lysine-coated gold nanorods at a dosage of 400 µM Au for 24 h undertake efficient uptake, i.e. around 3 pg Au per cell, retain the majority of their cargo until 24 h post-treatment and maintain around 90% of their pristine viability, chemotactic and pro-inflammatory functions.ConclusionsWith respect to previous models of cationic coatings, poly-l-lysine is a competitive solution for the preparation of biological vehicles of gold nanorods, especially for applications that may require longer life span of the Trojan horse, say in the order of 24 h. This biopolymer combines the cost-effectiveness of small molecules and biocompatibility and efficiency of natural peptides and thus holds potential for translational developments.
Highlights
The delivery of plasmonic particles, such as gold nanorods, to the tumor microenvironment has attracted much interest in biomedical optics for topical applications as the photoacoustic imaging and photothermal ablation of cancer
The plasmonic feature around 800 nm is a distinctive hallmark of gold nanorods with an aspect ratio around 4 [39, 42] and underwent no variation upon PEGylation and bio-conjugation, as was reported for mercaptoundecyl trimethyl ammonium bromide (MUTAB)- [29], cell penetrating peptides (CPPs)- [56] as well as sulfonamide- [66] and IgG- [67] coated gold nanorods that were protected with polyethylene glycol (PEG)
We have addressed the modification of gold nanorods as passenger particles for efficient coupling to tumortropic cells that may undertake their chemotactic delivery to a tumor site as a biological taxi, for imaging and therapeutic applications
Summary
The delivery of plasmonic particles, such as gold nanorods, to the tumor microenvironment has attracted much interest in biomedical optics for topical applications as the photoacoustic imaging and photothermal ablation of cancer. Borri et al J Nanobiotechnol (2018) 16:50 particles that convey contrast for applications as the photoacoustic imaging [19,20,21,22] and optical hyperthermia of cancer [23,24,25,26], which hold spatial resolution coarser than the single cell and are exempt of the final steps of the so-called CAPIR cascade (Circulation, Accumulation, Penetration, Internalization, and drug Release [3]) In this context, several authors have proposed different models of biological vehicles of plasmonic particles, including macrophages [27,28,29], T lymphocytes [30, 31], mesenchymal [32, 33] and neural [34, 35] stem cells or endothelial progenitors [36]. Gold nanorods represent a convenient choice, owing to their ease of synthesis and modulation of their longitudinal band of plasmonic oscillations in the near-infrared window of principal interest in biomedical optics [39,40,41,42,43]
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