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.

Tumor Microenvironment Targeted Nanotherapy

“…However, they have limitations, some peptides lack stability as they are scavenged (especially, cationic peptides) by reticulo-endothelial system (RES) and also specificity deficient for cancerous cell targeting, leading to toxicity. To circumvent this issue, new generation multistage ligand-mediated nano-chemotherapeutics that are responsive to tumor microenvironment are designed, which are classified as follows: (a) activatable CPPs (ACPPs), (b) de-shielding systems, (c) “pop-up” systems, and (d) trojan-horse targeting systems (for detailed review, refer, Chen B. et al, 2017 ; Kebebe et al, 2018 ). In ACPPs, tumor microenvironment responsive materials are exploited to display CPPs either at lower pH or in presence of overexpression of ECM development-remodeling proteases, or in response to external stimuli of heat or light to a disease site (MacEwan and Chilkoti, 2013 ).…”

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

“…16 It has been reported that encapsulation of anticancer drugs by nanoparticles could efficiently deliver drugs to tumor sites through an EPR effect and superior pharmacokinetics profiles in vivo, resulting in prolonged drug circulation and reduced systemic toxicity in vivo. 17 MPEG-PLA nanoparticles show high EE, stability and low clearance, which make it as a promising delivery tool for chemotherapeutic drugs. The amphiphilic property of MPEG-PLA enables the nanoparticles to selfassemble to be micelles and form a core-shell structure during the process of rehydration.…”

<p>Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment</p>

“…In our previous report, we reviewed the classification of polypeptide-and polypeptide-modified nanocarriers in detail. 258 In this report, recent research progress is summarized in the following paragraphs.…”