Direct photoacoustic measurement of silicon nanoparticle degradation promoted by a polymer coating

https://doi.org/10.1016/j.cej.2021.132860Get rights and content

Highlights

  • Photoacoustic method for measurement of nanoparticle degradation was introduced.

  • Photoacoustic showed polyallylamine coat promoted silicon nanoparticle dissolution.

  • Polyallylamine-coated silicon particles blocked macrophages in vitro and in vivo.

  • Blockade by silicon particles enhanced tumour uptake of magnetic particles 13-fold.

Abstract

Nanomaterials with controllable biodegradation properties respond to the main challenge of cancer nanomedicine to minimise side effects and maximise the delivery efficacy to tumours. These biodegradation properties vary from clear aqueous solutions to protein-abundant biological fluids. A photoacoustic method suitable for in vitro quantification of highly scattering colloids with optical absorption properties is introduced and demonstrated by determination of the degradation rate of laser-synthesized silicon nanoparticles (Si NPs) in turbid serum solutions. In vitro screening of a variety of polymer surface-coatings of Si NPs revealed a stand-alone property of polyallylamine (PAA) to accelerate the Si NP dissolution. PAA-coated Si NP half-life was measured ∼ 100-min in aqueous solutions and slowed down to ∼ 24 h in serum. As-produced PAA-coated Si NPs appeared suitable for blockade of the mononuclear phagocyte system. Pre-treatment with PAA-Si NPs caused 1.4-times reduced uptake of magnetic particles by human THP-1 cells in vitro and a 13-fold increase of the magnetic particle delivery to the B16-F1 xenograft tumours in vivo. The demonstrated photoacoustic method is believed to facilitate design and screening of biodegradable materials suitable for in vivo applications such as controlled drug release.

Introduction

Nanotechnology has potential to shift the paradigm of cancer therapy and diagnostics by enabling high-contrast intravital imaging, efficient targeted drug delivery and controlled drug release kinetics for improved patient compliance [1], [2]. Safe applications of nanoparticles (NPs) in medicine require rapid clearance of NP material from the organism at the completion of the pharmacodynamics cycle. These requirements for the next-generation nanomedicine call for new biomaterials with controllable long-term fate.

The nanomaterial clearance is commonly achieved by NP destruction or disassembly into clearable products, followed by their excretion from the body to minimise toxic stress exerted via oxidative [3] and inflammatory processes [4], changes in the activity of immune cells [5], etc. Despite a wealth of reported biodegradable nanomaterials, including polymeric [6], inorganic [7] and stimuli-responsive NPs [8], scanty publications report on the degradation kinetics control of NPs from their production stage through to biodegradation in a living organism. In biological fluids like serum, NPs interact with a plethora of molecules by binding to proteins, activate complement, etc [9], [10], and, as a result, a protein corona is formed on the surface of the NPs. The protein corona formation modulates the biodegradation kinetics [11] whose observation is eclipsed by the turbidity of most biological fluids.

Most analytical methods for assaying degradation of NPs in biological fluids are destructive. These include “gold standards” in biology, such as inductively coupled plasma mass spectroscopy, atomic absorption spectroscopy and transmission electron microscopy (TEM) [12], [13]. These methods are expensive, time-consuming, and cumbersome, unable to capture the system evolution in the full context of the NP interaction with biological environment. These methods are difficult to implement for high-throughput material degradation screening in physiological conditions.

In comparison with the destructive NP measurement methods, non-destructive analytical methods are preferable and actively developed. Of these, dynamic light scattering [14], spectrophotometry [15] can report on the mean size of colloidal NPs and allow in vitro measurement to acquire the NP degradation kinetics. However, these methods require clear or translucent solutions and are often incompatible with protein, serum solutions, whole blood, and not suitable for measurements in turbid cell solutions. An alternative approach relies on labelling NPs with contrast agents to render NPs detectable in biological systems. The labels include photoluminescent materials [12], radioisotopes [16], and magnetic contrast agents [17], [18], [19]. However, these approaches commonly provide qualitative evaluation of the NP integrity, whereas the quantitative evaluation is typically limited to a narrow range of concentrations. Besides, the detected signal reflects the label status as affected by biological microenvironment and may be decoupled with the status of the nanomaterial, leading to measurement artefacts [20].

These days, a range of nano-sized optical absorbers is rapidly expanded due to the growing interest in optical imaging in the biological tissue transparency window (wavelength range, 700 nm – 1350 nm). These nanomaterials include plasmonic NPs widely used for hyperthermic treatments [21], upconversion nanoparticles for photosensitisation in photodynamic therapy [22], shortwave infrared NPs for deep biological tissue imaging [23]. The use of absorbing NPs for photoacoustic imaging is of particular note due to the unprecedented imaging depth of several centimetres reported in literature [24] and diagnostics potential demonstrated for detection of circulating tumour cells [25].

In this paper, we report on the development of photoacoustic technique for direct in vitro observation of the long-term fate of a broad class of optical absorbing nanomaterials. We chose silicon NPs with reported dissolution properties [26] as an example of the light absorbing nanomaterial to demonstrate the power of the photoacoustic method for measuring degradation kinetics of particles with surface-engineered properties in various colloidal solutions. We found that unlike many other screened polymers, positively charged polyallylamine (PAA) promoted NP degradation in aqueous and serum solutions in vitro. The PAA-coated Si NPs were deployed to demonstrate macrophage blockade both in vitro and in vivo. The macrophage blockade resulted in a 10% decrease of the liver uptake of secondly administrated magnetic nanoparticles and a 13-fold increase of their accumulation in the tumour. The introduced photoacoustic technique paves way for direct observation of the fate of absorbing NPs in highly scattering biological fluids and thereby facilitates designing and screening of biodegradable materials for in vivo applications.

Section snippets

Chemicals

Sodium chloride, potassium ferrocyanide, potassium chloride, sodium phosphate dibasic, potassium dihydrogen phosphate, sodium carbonate, sodium bicarbonate, sodium citrate, citric acid, hydrochloric acid, sodium hydroxide, polyallylamine solution (Mw 15 000), lipopolysaccharides from E. coli (LPS), resazurin sodium salt, nitric acid were purchased from Sigma–Aldrich (USA). Bovine serum albumin (BSA) was purchased from Merck Millipore (USA). DMEM medium, fetal bovine serum were purchased from

Synthesis and characterization of Si NPs

Silicon nanoparticles (Si NPs) were chosen as biodegradable nanomaterial reported in literature [26], [29] to evaluate our in vitro photoacoustic detection methodology and systematically investigate Si NP dissolution kinetics. The choice of Si NPs was motivated by their proven merits. Silicon-based nanomaterials have been used for in vivo delivery of drugs, genetic materials, and contrast dyes. In addition, Si NPs hold promise for radiofrequency thermal therapy and photodynamic therapy [30],

Discussion

Biocompatible material has been consented to be biodegradable, while the biodegradability is interpreted broadly from hours to months [12], [29], [42], but the faster degradation time matching the time of the nanomedicine action (i.e. hours) is preferred. Silicon is also considered degradable material, but its degradation half-life significantly slows down in the absence of pores or doping in the composition of nanoparticles, as well as when the surface is oxidised or coated with proteins or

Conclusion

We report on the application of a photoacoustic detection method for direct in vitro measurement of nanomaterial content and degradation kinetics in aqueous, buffer, and serum solutions. Silicon nanoparticles (Si NPs) with strong absorption in visible range and proven biodegradation properties were chosen as the photoacoustic nanomaterial. The degradation rate of bare and polymer-coated Si NPs was significantly slowed down in serum solutions, with one notable exception – positively-charged

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The work was supported by the Ministry of Science and Higher Education of the Russian Federation, agreement no. 075-15-2020-773.

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