Self-assembled non-covalent protein-drug nanoparticles: an emerging delivery platform for anti-cancer drugs

ABSTRACT

Introduction

Protein nanocarriers offer advantageous delivery platforms for anti-cancer drugs, provided by their biocompatibility, high drug loading capacity, and their ability to encapsulate hydrophobic active therapeutics. However, the conventional fabrication techniques of protein nanoparticles (NPs) often suffer from incorporation of considerable amounts of toxic solvents and crosslinking agents which may result in significant toxicity or compromise the drug stability. Therefore, novel strategies were proposed to induce non-covalent self-assembly of proteins by exploiting hydrophobic interactions or manipulation of disulfide bonds to produce nontoxic crosslinker-free drug-loaded protein NPs. Thermal mediated unfolding, the use of reducing agents, modulation of pH and ionic strength, chemical-induced denaturation as well as photochemical methods can be efficiently utilized to induce the protein self-assembly process.

Areas covered

In this review, we highlight the novel approaches used in the development of non-covalent protein-drug nano-assemblies, formulation factors, their implications, limitations, and treatment outcomes as well as future challenges.

Expert opinion

Formulation of protein-drug nanocarriers via non-covalent self-assembly can be advantageous as a promising strategy for efficient and safe tumor-targeted delivery of anti-cancer drugs compared to the conventional nano-fabrication technologies.

WORDS:

• Protein nanoparticles
• non-covalent self-assembly
• anti-cancer drugs
• protein unfolding
• hydrophobic interactions
• thermal treatment
• disulfide bond reduction

Article highlights

• Protein nanocarriers are versatile drug delivery systems, however, strategies employed in the fabrication of protein nano-carriers are often compromised by several limitations.

• Novel strategies were proposed to induce non-covalent self-assembly of proteins by exploiting hydrophobic interactions or manipulation of disulfide bonds to produce non-toxic crosslinker-free drug-loaded protein nanoparticles.

• Thermal mediated unfolding, the use of reducing agents, modulation of pH and ionic strength, chemical-induced denaturation as well as photochemical methods can be efficiently utilized to induce the protein self-assembly process.

• Non-covalent self-assembled protein nanocarriers offer several implications, including Targeting, enhanced cytotoxicity, reduced toxicity, improved bioavailability, cancer theranostics, and Stimuli-responsive drug release.

• Although, the novel methods for the fabrication of protein nano-assemblies offer several advantages, some major drawbacks may hinder their scaling-up, including toxicity profiles for some proteins as well as some incorporated disulfide bond reductants.

This box summarizes key points contained in the article.

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 not funded.