Use of nanotechnology for improved pharmacokinetics and activity of immunogenic cell death inducers used in cancer chemotherapy

ABSTRACT

Introduction: Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers.

Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology.

Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.

KEYWORDS:

• Immunogenic cell death inducers
• Damage-Associated Molecular Patterns
• Calreticulin
• ATP
• HMGB1
• nanocarriers
• liposomes
• polymeric micelles
• metronomic therapy

Article highlights

• Immunogenic cell death (ICD) is one of the new  concepts used to activate adaptive immune response of the host.

• Actually known ICD inducers suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their applications.

• Nanotechnology providing an excellent tool to improve the activity (and often decrease the toxicity) of practically all substances used in pharmacology and medical imaging techniques.

• There are at least three key drug-delivery systems (liposomes, polymeric micelles and some nanoparticles) which have great potential to exploit the ICD inducers phenomenon.

• The detailed chemical and biophysical understanding concerning the pharmacokinetic behavior of lipid based delivery systems is now opening up a whole new field in terms of ‘designer’ properties uniquely and specifically tailored for both optimal and specific performance in different cancers and tissues, in terms of stability, uptake, targeting, delivery, release and therapeutic effect.

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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.

Additional information

Funding

This paper was not funded.