Overcoming the stability, toxicity, and biodegradation challenges of tumor stimuli-responsive inorganic nanoparticles for delivery of cancer therapeutics

ABSTRACT

Introduction: Stimuli-responsive nanomaterials for cancer therapy have attracted much interest recently due to their potential for improving the current standard of care. Different types of inorganic nanoparticles are widely employed for the development of these strategies, but in some cases safety concerns hinder their clinical translation. This review aims to provide an overview of the challenges that inorganic nanoparticles face regarding their stability, toxicity, and biodegradability, as well as the strategies that have been proposed to overcome them.

Areas covered: The available information about the in vitro and in vivo biocompatibility, as well as the biodegradability of the following nanoparticles, is presented and discussed: superparamagnetic iron oxide nanoparticles, gold nanoparticles, graphene and mesoporous nanoparticles made of silicon or silicon oxide. The toxicology of inorganic nanoparticles is greatly affected by many physicochemical parameters, and their surface modification emerges as the main intervention to improve their biocompatibility and tailor their performance for specific biomedical applications.

Expert opinion: Even though many different studies have been performed regarding the biological behavior of inorganic nanoparticles, long-term in vivo data is still scarce, limiting our capacity to evaluate the proposed nanomaterials for clinical use. The role of biodegradability in different therapeutic contexts is also discussed.

KEYWORDS:

• Inorganic nanoparticles
• mesoporous silica nanoparticles. nanomedicine
• nano-toxicology
• superparamagnetic iron oxide nanoparticles

Article highlights

• A series of inorganic nanoparticles have become fundamental tools in the development of stimuli-responsive nanoparticles for oncological treatment, making necessary their nano-toxicological evaluation.

• SPION have been employed as drug delivery systems and magnetically triggered heaters. These nanoparticles present potential toxicity by the production of radical oxidative species but this undesired property has been diminished by tuning their size and/or coating their surface with different moieties.

• GNP present unique optical properties which have been exploited for the production of hyperthermia seeds triggered by near-infrared radiation and imaging agents in combination with drug delivery agents. Their biocompatibility is excellent but they are barely degraded in physiological conditions. Therefore, their potential toxicity should be evaluated in long time assays.

• Graphene has been thoroughly studied for drug and gene delivery, biosensing and imaging. Some studies have shown potential toxicity in physiological and pathological conditions, although the chemical modification and surface coating with different polymers can improve its biocompatibility profile.

• Mesoporous particles made of silicon or silica present many advantages as drug delivery systems. Their biodegradability can be controlled by modifying a series of physicochemical parameters, which enables tailoring these materials for specific biomedical applications and preventing their long-term bioaccumulation.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the European Research Council (Grant VERDI; ERC-2015 AdG no. 694160). JL Paris is supported by a post-doctoral fellowship from the Ramón Areces Foundation.