Cancer active targeting by nanoparticles: a comprehensive review of literature

Abstract

Purpose: Cancer is one of the leading causes of death, and thus, the scientific community has but great efforts to improve cancer management. Among the major challenges in cancer management is development of agents that can be used for early diagnosis and effective therapy. Conventional cancer management frequently lacks accurate tools for detection of early tumors and has an associated risk of serious side effects of chemotherapeutics. The need to optimize therapeutic ratio as the difference with which a treatment affects cancer cells versus healthy tissues lead to idea that it is needful to have a treatment that could act a the "magic bullet"-recognize cancer cells only. Nanoparticle platforms offer a variety of potentially efficient solutions for development of targeted agents that can be exploited for cancer diagnosis and treatment. There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves.

Methods: Relevant English electronic databases and scientifically published original articles and reviews were systematically searched for the purpose of this review.

Results: In this report, we present a comprehensive review of literatures focusing on the active targeting of nanoparticles to cancer cells, including antibody and antibody fragment-based targeting, antigen-based targeting, aptamer-based targeting, as well as ligand-based targeting.

Conclusion: To date, the optimum targeting strategy has not yet been announced, each has its own advantages and disadvantages even though a number of them have found their way for clinical application. Perhaps, a combination of strategies can be employed to improve the precision of drug delivery, paving the way for a more effective personalized therapy.

Fig. 1

A schematic illustration showing methods used for active targeting of nanoparticles. I Antibody-based targeting, which involves the use of A monoclonal antibodies such as anti-Her2/neu antibody directed toward Her2/neu receptors on the target cell membrane, (B)antibody fragments: single-chain variable fragments (scFV) such as single-chain anti-epidermal growth factor receptor (EGFR) antibody directed toward EGFR, or antigen-binding fragment (Fab) such as anti-Her2/neu Fab. II Aptamer-based targeting such as the A10 RNA aptamer directed toward prostate-specific membrane antigen (PSMA) on the surface of the target cells. III Ligand-based targeting such as (A)transferrin-based targeting of nanoparticles toward transferrin receptors where uptake of the nanoparticles takes place through receptor-mediated endocytosis through clathrin-coated pits, (B) folate-based targeting using folic acid to target folate receptor alpha (FRα), which is upregulated on the surface of neoplastic cells

Fig. 2

A schematic illustration showing the principle of cell-based systemic evolution of ligands by exponential enrichment (SELEX) for generation of aptamers based on their capability of recognizing complex molecular signatures of cancer cells rather than a single target on the cell membrane. Initially, a single-stranded nucleic acid (RNA/DNA) library is prepared (30–40 nucleotides in length flanked by primer sequences) followed by incubating the oligonucleotide library with a target cancer cell. The unbound DNA probes are washed out, and the bound ones are then collected and incubated with negative control cells for counter selection. All unbound probes are collected and amplified using polymerase chain reaction (PCR), and the evolved DNA pool is cloned and sequenced to determine the sequence of specific aptamers