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

Abstract

Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti‐cancer drugs are severely restricted from reaching the tumour site. Cell‐penetrating peptides (CPPs) are typically made up of 5–30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti‐cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs‐based drug delivery strategy could be improved by clever design or chemical modifications to develop the next‐generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

Chicken skin-derived collagen peptides chelated zinc promotes zinc absorption and represses tumor growth and invasion in vivo by suppressing autophagy

“…In this study, we found that the < 5 kDa CCP showed good anti-tumor activity. A lot of anti-tumor peptides have been found in recent years because of their advantages of targeting, specificity, safety, and so on ( 57 , 58 ). The anti-tumor mechanisms of these peptides are diversified: direct anti-tumor effect can be achieved by inhibiting the proliferation of tumor cells and promoting the apoptosis of tumor cells, or indirect anti-tumor effect can be achieved by enhancing and stimulating the immune response of the body to tumor cells, or by inhibiting the formation of tumor blood vessels ( 58 , 59 ).…”

Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer

“…Given that some CPPs lack tumor-specificity which could lead to drug delivery to cells in healthy tissues, there have been several attempts to enhance the specificity of CPPs-based delivery by taking advantage of the natural targeting abilities of antibodies and antigens [ 140 , 141 , 142 , 143 , 144 ]. For instance, by linking the antibody against tumorous cells’ highly expressed antigens to a CPP-siRNA complex, siRNA gene-drug delivery can be achieved with high levels of specificity and little cytotoxicity [ 145 ].…”

Approaches for evaluation of novel CPP-based cargo delivery systems

“…Biocompatibility and maintenance of viability of normal cells are another aspect to consider in CPP-mediated delivery. On the other hand, if the target of the CPP-cargo is to reduce the proliferation of aberrant cells, such as cancer cells, the reduction of viability for those cells would be welcome (Zhou et al, 2022). Although some general online tools (Table 1) are available for predicting toxicity, or immunogenicity, allergenicity, the possible effects should be confirmed experimentally.…”