Peptide Drug Conjugates and Their Role in Cancer Therapy

Abstract

Drug conjugates have become a significant focus of research in the field of targeted medicine for cancer treatments. Peptide-drug conjugates (PDCs), a subset of drug conjugates, are composed of carrier peptides ranging from 5 to 30 amino acid residues, toxic payloads, and linkers that connect the payload to the peptide. PDCs are further broken down into cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs), each having their own differences in the delivery of cytotoxic payloads. Generally, PDCs as compared to other drug conjugates—like antibody-drug conjugates (ADCs)—have advantages in tumor penetration, ease of synthesis and cost, and reduced off-target effects. Further, as compared to traditional cancer treatments (e.g., chemotherapy and radiation), PDCs have higher specificity for the target cancer with generally less toxic side effects in smaller doses. However, PDCs can have disadvantages such as poor stability and rapid renal clearance due to their smaller size and limited oral bioavailability due to digestion of its peptide structure. Some of these challenges can be overcome with modifications, and despite drawbacks, the intrinsic small size of PDCs with high target specificity still makes them an attractive area of research for cancer treatments.

Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs

“…Due to its clinical, biological and molecular complexity, OC is a tumor that is difficult to treat and lacks a clear driver mutation. Targeted therapies are now a strong focus for OC [ 71 , 72 ].…”

Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic

“…There is a broad spectrum of linker bonds undertaken for the designing of excellent PDCs, which are divided into two main categories (1) cleavable linkers that can be cleaved chemically and/or enzymatically such as pH-sensitive, redox-sensitive, enzyme-sensitive, and (2) noncleavable linkers include thioether, oxime, triazole, and carbon chain containing bonds . Many researchers have reviewed the detailed descriptions of differential behaviors and types of various cleavable and noncleavable linkers in depth highlighting the importance and divergent application in the construction of peptide–drug conjugates (PDCs). ,,, Herein, we will briefly summarize the main types of most efficiently used linkers utilized widely for the construction of PDCs, as listed in Table . The in vivo stability of the linkers has been assured and the reactivity order from topmost to the least one is as follows: amide > carbamate > ester > carbonate bonds .…”

“…161 Many researchers have reviewed the detailed descriptions of differential behaviors and types of various cleavable and noncleavable linkers in depth highlighting the importance and divergent application in the construction of peptide−drug conjugates (PDCs). 22,26,81,162 Herein, we will briefly summarize the main types of most efficiently used linkers utilized widely for the construction of PDCs, as listed in Table 6. The in vivo stability of the linkers has been assured and the reactivity order from topmost to the least one is as follows: amide > carbamate > ester > carbonate bonds.…”

“…Peptide-based active targeting ligands pave the beneficial route of delivering higher concentrations of CTs to internalize into the cancer cells by specifically targeting the cell surface receptors overexpressed at the tumor site. There are a few noteworthy differences (immunogenicity, penetration, and elimination) between a PDC and an ADC as described in Table , , which highlights the superiority of targeting peptide probes over the prerequisite antibodies for drug delivery applications. The biomedical research within the drug delivery consists of two groups: (i) small molecules (traditional CTs, NSAIDs, steroids, etc.)…”

Small Molecule–Drug Conjugates Emerge as a New Promising Approach for Cancer Treatment

“…By integrating the above three characteristics, SMDCs have the advantages of fast distribution and clearance, good penetration of solid tumors, nonimmunogenicity, clear chemical composition, and easy synthesis , and can be used for targeted delivery of chemical drugs …”