Actively targeted nanocarriers for drug delivery to cancer cells

ABSTRACT

Introduction: Progressive breakthroughs in nanomedicine have been instrumental for the clinical translation of actively targeted drug-delivery approaches. Besides storing large payloads of drugs within the nanoparticle core, the conjugation of targeting moieties confers specific targeting ability to the nanoplatforms. In this respect, clinical results suggest that actively targeted nanocarriers can exhibit an overall improved antitumor efficacy, minimizing off-target toxicity.

Areas covered: This review article summarizes the advances in active targeting of nanocarriers to cancer cells. Specifically, we discuss the various types of nanocarriers, describe the receptors that are frequently overexpressed in solid tumors, and discuss how this approach can be used to improve clinical outcomes. We particularly focus on ongoing clinical trials of actively targeted nanoparticles that are yet to be clinically approved.

Expert opinion: Further investment in active targeting will likely pose clinical benefits. We envisage a future requiring the use of longitudinal measures in the clinical setting to profile the patients that are likely to benefit from actively targeted nanocarriers. At the preclinical stage, a complete picture of intratumoral barriers combined with a quantitative approach of the intratumoral fate of nanomaterials will be instrumental in defining more effective strategies to improve their clinical translation.

KEYWORDS:

• Nanoparticles
• targeting
• drug delivery
• cancer cells
• receptors

Article highlights

• Active targeting of nanocarriers offers the opportunity to deliver a specific drug to a specific cell resulting in enhanced efficacy and reduced side effects.

• Even if the nanocarrier is designed for active targeting to arise, at first passive accumulation (EPR effect) occurs followed by target-specific binding as a complementary strategy.

• The extent of EPR effect is influenced by the heterogeneity of tumors and dynamic status of each tumor that need to be further investigated.

• Nanoparticles engineering has evolved rapidly in the last decade and their contribution to cancer research is increasing in parallel, facilitating the preclinical to clinical translation of selected actively targeted nanocarriers.

• Recent evidences from preclinical studies indicate that exosomes represent one of the most promising innovative drug delivery system for improving traditional chemotherapy, gene silencing as well as immunotherapy of tumors.

• EGFR, PSMA, transferrin, and folate receptors are the most advanced active-targeting strategies based on the concept that these antigens are overexpressed on cancer cell membranes.

• At present, few nanoparticle types are in clinical trials for cancer drug delivery, mainly formulated with liposomes or polymeric materials; however, new kinds of nanoparticles are expected to enter clinical trials in the near feature.

Exciting results are emerging from Phase I and II clinical trials of targeted retroviral nanoparticles.

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.