Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted ‘magic bullets’ to self-navigated ‘magic missiles’

ABSTRACT

Introduction: New phage-directed nanomedicines have emerged recently as a result of the in-depth study of the genetics and structure of filamentous phage and evolution of phage display and phage nanobiotechnology. This review focuses on the progress made in the development of the cancer-targeted nanomaterials and discusses the trends in using phage as a bioselectable molecular navigation system.

Areas covered: The merging of phage display technologies with nanotechnology in recent years has proved promising in different areas of medicine and technology, such as medical diagnostics, molecular imaging, vaccine development and targeted drug/gene delivery, which is the focus of this review. The authors used data obtained from their research group and sourced using Science Citation Index (Web of Science) and NCBI PubMed search resources.

Expert opinion: First attempts of adapting traditional concepts of direct targeting of tumor using phage-targeted nanomedicines has shown minimal improvements. With discovery and study of biological and technical barriers that prevent anti-tumor drug delivery, a paradigm shift from traditional drug targeting to nanomedicine navigation systems is required. The advanced bacteriophage-driven self-navigation systems are thought to overcome those barriers using more precise, localized phage selection methods, multi-targeting ‘promiscuous’ ligands and advanced multifunctional nanomedicine platforms.

KEYWORDS:

• Cancer
• nanomedicines
• drug delivery
• gene delivery
• landscape phage
• nanobiotechnology
• phage display
• phage proteins

Article highlights

• With development of nanomedicines, significant progress towards targeted cancer chemotherapy have been achieved, mostly through exploring passive targeting based on Enhanced Permeability and Retention (EPR) effect.

• Following the traditional ‘magic bullet’ concept, the active targeting of nanomedicines has been proposed to enhance their therapeutic efficacy and decrease side effects in patients.

• The low efficacy of numerous nanomedicines in biological experiments could be associated with inability of nanomedicines to penetrate through the complex tumor microenvironment into the core of tumors.

• With the goal of using phages as tumor-navigating probes in vivo, p8 expressing phages become invaluable analytical research and construction material.

• ‘Self-navigating phages’ can be selected from multivalent phage display libraries during migration from blood stream towards the tumor cells in cancer patients

• Advanced bacteriophage-driven self-navigation systems are thought to overcome organismic biological barriers using more precise, localized phage selection methods, multi-targeting ‘promiscuous’ ligands and advanced nanomedicine platforms.

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Declaration of interest

The authors have no other 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 apart from those disclosed.

Additional information

Funding

The authors would like to acknowledge the Auburn University Research Initiative in Cancer (AURIC) and the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award numbers [1U54CA151881 & R01CA125063] for financial assistance The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Auburn University. The authors received no payment in the preparation of this manuscript.