Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy

Abstract

With rapidly growing knowledge in bioinformatics related to peptides and proteins, amino acid-based drug-design strategies have recently gained importance in pharmaceutics. In the past, peptide-based biomedicines were not widely used due to the associated severe physiological problems, such as low selectivity and rapid degradation in biological systems. However, various interesting peptide-based therapeutics combined with drug-delivery systems have recently emerged. Many of these candidates have been developed for anticancer therapy that requires precisely targeted effects and low toxicity. These research trends have become more diverse and complex owing to nanomedicine and antibody–drug conjugates (ADC), showing excellent therapeutic efficacy. Various newly developed peptide–drug conjugates (PDC), peptide-based nanoparticles, and prodrugs could represent a promising therapeutic strategy for patients. In this review, we provide valuable insights into rational drug design and development for future pharmaceutics.

Peptide-Drug Conjugates: A New Hope for Cancer Management

“…However, new methodologies are being developed to overcome such factors. Thus far, two PDCs are available in the market, (i) Lu 177 -dotatate (somatostatin as homing peptide conjugates with a radio-therapeutic agent) used for the treatment of gastroenteropancreatic neuroendocrine tumors [ 42 ], and (ii) melphalan flufenamide (melflufen), an allogeneic first-in-class peptide-drug conjugate, approved by the US Food and Drug Administration (USFDA) in 2021 for the treatment of multiple myeloma [ 42 ], with several others in various phases of development ( Table 1 ).…”

“…Self-assembled nanoparticles are advantageous as they show diversity in their chemical makeup, are biocompatible, enable high loading capacity of peptides and/or drugs, and can target sites on cancer cells. In fact, the peptide KLA (acetyl-KLAKLAK) 2 -NH 2 ) conjugated with a tumor-homing peptide iRGD (CRGDKGPDC) has improved penetration of low-grade tumor tissue and cells with high selectivity and low systemic toxicity [ 42 , 183 ].…”

“…A protein-G-derived albumin-binding domain (ABD) conjugated with doxorubicin via a pH-sensitive linker demonstrates a longer half-life in the plasma and four times higher accumulation within the tumor [ 182 ]. Albumin-binding peptide (DICLPRWGCLW)-based bioconjugates are stable complexes for tumor-targeting effect [ 42 , 182 ].…”

“…The treatment of cancer can be possible by controlling the function of immune cells [ 42 ]. Programmed cell death ligand (PD-L1) is overexpressed on several cancer cells [ 187 , 188 , 189 , 190 ].…”

“…Peptide targeting itself is becoming combinatorial with the use of more than one peptide in a single entity, the use of peptides that also serve as proteolytic substrates to provide more function [ 206 ]. The further development of self-assembly peptide-based nanotechnology can promise highly effective anti-cancer therapeutic options [ 42 ]. Figure 3 presents different types of peptides which nanoparticles can deliver and provide a more efficient therapeutic impact for cancer treatment.…”