A Heparan Sulfate-Binding Cell Penetrating Peptide for Tumor Targeting and Migration Inhibition

Abstract

As heparan sulfate proteoglycans (HSPGs) are known as co-receptors to interact with numerous growth factors and then modulate downstream biological activities, overexpression of HS/HSPG on cell surface acts as an increasingly reliable prognostic factor in tumor progression. Cell penetrating peptides (CPPs) are short-chain peptides developed as functionalized vectors for delivery approaches of impermeable agents. On cell surface negatively charged HS provides the initial attachment of basic CPPs by electrostatic interaction, leading to multiple cellular effects. Here a functional peptide (CPPecp) has been identified from critical HS binding region in hRNase3, a unique RNase family member with in vitro antitumor activity. In this study we analyze a set of HS-binding CPPs derived from natural proteins including CPPecp. In addition to cellular binding and internalization, CPPecp demonstrated multiple functions including strong binding activity to tumor cell surface with higher HS expression, significant inhibitory effects on cancer cell migration, and suppression of angiogenesis in vitro and in vivo. Moreover, different from conventional highly basic CPPs, CPPecp facilitated magnetic nanoparticle to selectively target tumor site in vivo. Therefore, CPPecp could engage its capacity to be developed as biomaterials for diagnostic imaging agent, therapeutic supplement, or functionalized vector for drug delivery.

Cell Penetrating Peptide as a High Safety Anti-Inflammation Ingredient for Cosmetic Applications

“…It has been reported that TAT can be apply for topical drug-delivery, but high cell penetrating activity might increase some risks which is that TAT might bring drug penetrating cell-layers into deeper tissues [30]. Unlike TAT, our CPPAIF only penetrate into cytosol of epidermal cells without exocytosis property [21], hence it would not be a concern of drug effect. Environmental conditions of skin surface might be tough for bio-molecules (peptide).…”

“…Here a 10-residue peptide, covering major GAG binding motif of a human ribonuclease, is identified as a CPP AIF (anti-inflammatory CPP). CPP AIF has been shown to possess epithelial cell, GAG and lipid binding properties as well as cell penetrating activity through macropinocytosis [20,21]. Notably, CPP AIF is able to deliver small fluorescent molecules, recombinant proteins, nanoparticles, and peptidomimetic drugs into cells [20].…”

Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation

“…ECP and CPPecp both bind to HSPGs on cell surface and have cell penetrating characters, as we have demonstrated previously 7 – 9 . CPPecp, the unique sequence derived from human ECP, has been demonstrated to be different from conventional GAG binding CPPs 8 , 22 , 23 . Recent reports showed that HS binding activity may interfere with in vivo functions of most HS-binding soluble modulators such as IL-4, IL-8, CCL11, and vascular endothelial growth factor (VEGF) in immune response 3 , 24 .…”

The role of cell‐penetrating peptides in potential anti‐cancer therapy

“…In addition, the combination of anti-cancer drugs and CPPs can increase the cell membrane permeability, drug delivery, drug half-life and accumulation in tumour cells. 149 Next, based on the combination of CPPs and various anti-tumour drugs, we will discuss the targeted inhibition effects on different tumour cells. Five anti-tumour drugs are natural anti-tumour drugs, antibiotic antineoplastic drugs, platinum chemotherapeutic drugs, antimetabolite antineoplastic drugs and hormone anti-tumour drugs.…”