Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

Abstract

Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

Keywords: cancer; cell-penetrating peptide; herb-based drug; nanocarriers; targeting drug delivery; tumor targeting.

Figure 1

Passive and active targeting of tumors. Note: In passive targeting, drug-loaded NPs discriminately accumulate in tumor tissue due to leaky vasculature and poor lymphatic system, whereas active targeting involves the binding of ligand modified NPs to the receptor that are overexpressed on the cancer cells and directing cell membrane penetration using CPP. Abbreviations: NPs, nanoparticles; CPP, cell-penetrating peptide; EPR, enhanced permeability and retention.

Figure 2

Activable cell-penetrating peptides (CPPs). Note: Enzyme-activated CPP (A), photon-activated CPP (B), pH-activated CPP (C).

Figure 3

Chemical structure of some plant-derived anticancer drugs.