Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells

Abstract

Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility has encouraged the use of peptides as highly specific carriers as short peptides are usually non-antigenic, are structurally simple and synthetically diverse. Recent years have seen many developments in the field of peptide based drug conjugates (PDCs), particularly for cancer therapy, as their use aims to bypass off-target side-effects, reducing the morbidity common to conventional chemotherapy. However, no PDCs have as yet obtained regulatory approval. In this review, we describe the evolution of the peptide-based strategy for targeted delivery of chemotherapeutics and discuss recent innovations in the arena that should lead in the near future to their clinical application.

Sequence modification of heptapeptide selected by phage display as homing device for HT-29 colon cancer cells to improve the anti-tumour activity of drug delivery systems

“…Peptides having high binding affinities to tumour selective or overexpressed receptors in cancer cells are useful because of their simple structure, low immunogenicity and easy, cost-effective chemical synthesis compared to antibody drug conjugates (ADCs). In the last decades, many developments have been done in the field of peptide based small molecule drug conjugates (SMDCs), particularly for cancer therapy [9]. However, the efficacy of these conjugates was studied rather individually on cancer cells.…”

Trimethyl Lock: A Multifunctional Molecular Tool for Drug Delivery, Cellular Imaging, and Stimuli‐Responsive Materials

“…If attached at an appropriate distance, quinones can serve as electron acceptors for excited fluorophores, and this leads to fluorescence quenching by reductive photoinduced electron transfer (PeT). [100] Among the tumor-targeting small molecules showing high affinity for receptors overexpressed on certain cancer cell lines, [101,102] vitamins are some of the most effective;t hese molecules can mediate the uptake of conjugates owing to their generally high demandi nr apidly proliferating cancer cells, their stability towards metabolic processes, and their generally low potentialt oa ctivate autoimmune responses. [93] After entering NQO1-overexpressingc ancer cells, the quinone moiety of resultingn onfluorescent prodrug 67 is reduced to corresponding dihydroquinone 68 ( Figure 2B), and this initiates ac ascade consisting of the rapid lactonizationo ftheT ML moiety,f ollowed by a1 ,6-elimination of the p-aminobenzyl alcohol unit.…”

“…The principle to mask the fluorescenceo fC PT in quinonebased prodrugs has also been recently used by Kim and coworkers in designing extracellular-targeted biotin-CPT conjugate 79 (Scheme 15). [100] Among the tumor-targeting small molecules showing high affinity for receptors overexpressed on certain cancer cell lines, [101,102] vitamins are some of the most effective;t hese molecules can mediate the uptake of conjugates owing to their generally high demandi nr apidly proliferating cancer cells, their stability towards metabolic processes, and their generally low potentialt oa ctivate autoimmune responses. [103][104][105] In particular, Bvitamins such as folic acid (vitaminB9), [106][107][108][109][110] cobalamin (vitaminB 12), [111][112][113][114] and biotin (vitaminB7) [115] have been shown to be promising candi- Scheme14.…”

A novel LRP1-binding peptide L57 that crosses the blood brain barrier

“…As targeting molecules, peptides are very attractive as they bind target proteins potently and selectively, and display technologies are available for discovering binding peptides [10] . Moreover, a variety of derivatization methods exist to ensure the generation of peptide analogs with adequate pharmacokinetic profiles; peptide analogs are prepared homogeneously by chemical synthesis.…”