Advances in nanotechnology-based platforms for survivin-targeted drug discovery

ABSTRACT

Introduction

Due to its unique functional impact on multiple cancer cell circuits including proliferation, apoptosis, tumor dissemination, DNA damage repair, and immune response, the inhibitor of apoptosis protein (IAP) survivin has gained high interest as a molecular target and a multitude of therapeutics were developed to interfere with survivin expression and functionality. First clinical evaluations of these therapeutics, however, were disappointing highlighting the need to develop advanced delivery systems of survivin-targeting therapeutics.

Areas covered

This review focuses on advancements in nanocarriers to molecularly target survivin in human malignancies. A plethora of nanoparticle platforms, including liposomes, polymeric systems, dendrimers, inorganic nanocarriers, RNA/DNA nanotechnology and exosomes, are discussed in the background of survivin-tailored RNA interference, small molecule inhibitors, dominant negative mutants or survivin vaccination or combined modality treatment with chemotherapeutic drugs and photo-dynamic/photothermal strategies.

Expert opinion

Novel therapeutic approaches include the use of biocompatible nanoformulations carrying gene silencing or drug molecules to directly or indirectly target proteins, allow for a more precise and controlled delivery of survivin therapeutics. Moreover, surface modification of these nanocarriers may result in a tumor entity-specific delivery. Therefore, nanomedicine exploiting survivin-tailored strategies in a multimodal background is considered the way forward to enhance the development of future personalized medicine.

KEYWORDS:

• Survivin
• nanotechnology
• molecular targeting
• nanoparticles
• cancer

Article highlights

• The development of strategies to molecularly target the tumor selective inhibitor of apoptosis protein survivin has shown great success in preclinical studies, but so far failed to indicate a benefit in clinical trials.

• Recent advances in nanotechnology have enhanced survivin targeting by the development of biodegradable nanocarrier delivery systems and exosomes that can increase drug availability and distribution and may allow multimodal therapeutic modalities including photo-dynamic/photothermal strategies and immune vaccination.

• Moreover, functionalization of NP surfaces by adding multiple functional groups, and tumor cell-specific antibodies will pave the way for developing more cancer entity- and tumor microenvironment-specific vehicles to target survivin.

• Finally, progress in survivin-tailored therapies using NPs is promising, however, further modifications of the nanocarriers and in vivo investigations using appropriate orthotopic models are required before these strategies can enter clinical validation.

This box summarizes key points contained in the article.

Funding

This manuscript was in part supported by a grant (FM01-10168) from the German Cancer Consortium (DKTK) partner site Frankfurt and the Clinical Translation Program of the LOEWE Center Frankfurt Cancer Institute (FCI).

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.

Reviewer Disclosures

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