Navigations of the targeting pathway of nanomedicines toward tumor

ABSTRACT

Introduction

Nanomedicines (NMs) have emerged as a promising approach for revolutionizing cancer treatment outcomes, mainly due to their benefits in the tumor-targeted delivery of therapeutics. The preferential accumulation of NMs in tumors has been widely verified by macroscopical technologies. Accordingly, several classic and emerging targeting mechanisms have been proposed to support the tumor-specific delivery of NMs. The targeting mechanism has been a topic of intense interest and controversy in the field of NMs development. Especially, the mechanisms by which NMs target tumor remain elusive.

Area covered

This topical review mainly discussed the evolution of the targeting mechanisms, crucial issues associated with each mechanism, and confused debates among the mechanisms. The targeting mechanisms of tumor-specific NMs discussed here include the enhanced permeability and retention (EPR) effect, protein corona-mediated targeting delivery, circulating cell mediated transportation, and transcytosis.

Expert opinion

It is of great significance for ultimate clinical translation to have more comprehensive considerations on the mechanism driving the pathway of NMs toward tumors. Our thoughts in this review are expected to provide a comprehensive understanding of the mechanisms and elicit thorough explorations of new mechanisms to renovate the knowledge framework of NMs delivery.

KEYWORDS:

• Nanomedicines
• EPR effect
• protein corona
• cell-mediated transportation
• targeting mechanism

Article highlights

• The focus of this topical review is to discuss the evolution of the classic and emerging mechanisms including enhanced permeability and retention (EPR) effect, protein corona (PC)-mediated targeting delivery, circulating cell-mediated transportation, and transcytosis. The crucial issues associated with each mechanism and some confusing debates among the mechanisms were proposed and discussed in-depth.

• Skepticism and controversy still exist in the EPR effect-mediated NMs toward tumor targeting delivery and the potential gaps between EPR effect and clinical therapeutic efficiency were fully discussed.

• The formation of protein corona (PC) around the surface of NMs is regarded as a huge obstacle to increase the accumulation of active targeting NMs at tumor sites. However, dissection of the crucial effects of pivotal component of PC facilitated a shift from PC-centric avoiding toward precise regulation of PC to achieve predictable biologic response.

• Employing circulating cells as drug delivery carriers has emerged as a new ‘living’ targeting pathway to reinforce the tumor targeted delivery efficiency of NMs with high mobility and low immunogenicity. The cell-NMs hybrids could be divided into ‘Trojan horse’ and ‘Cell backpack’ strategy and the underlying limitations of each strategy were explored thoroughly.

• Transcytosis is a complementary strategy for enhancing targeting ability of NMs at tumor sites including the receptor-mediated transcytosis (RMT) and the adsorptive-mediated transcytosis (AMT). Among the two strategies, ligand and charge modification were regarded as two key factors to decide the efficiency of transcytosis.

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.