Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

Abstract

Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11-loaded DSPE-PEG 2000 targeting EGFR liposomal delivery system and characterize its targeting specificity and therapeutic effect on colorectal cancer (CRC) cells in vitro and in vivo. Results The synthesized liposome exhibited spherical shapes (84.6 ± 1.2 nm to 150.4 nm ± 0.8 nm of estimated average sizes), good stability, sustained release, and enough drug loading (55.19%). For in vitro experiments, SW620 cells treated with CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome showed lower survival extended level of intracellular ROS production. In addition, it generated an enhanced apoptotic cell rate by upregulating the protein expression of both cleaved-caspase-3 and cleaved-caspase-9 compared with those of SW620 cells treated with free CPT-11. Importantly, the xenograft model showed that both the non-target and EGFR-targeted liposomes significantly inhibited tumor growth compared to free CPT-11. Conclusions Compared with the non-target CPT-11-loaded DSPE-PEG2000 liposome, CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome treatment showed much better antitumor activity in vitro in vivo. Thus, our findings provide new assets and expectations for CRC targeting therapy.

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

“…The epidermal growth factor receptor (EGFR or HER1) is a membrane protein that is highly overexpressed in cancer. Its molecular targeting often enhances drug antitumor activity [ 231 ]. The epidermal growth factor (EGF), due to its specific and strong binding to the receptor, was successfully used as a functionalization strategy in colon cancer drug delivery [ 232 , 233 ], by exploiting, for example, PLGA nanoparticles [ 234 ] or lipid-based systems [ 235 , 236 ].…”

“…In such a disease, several membrane proteins are known to be overexpressed and can be used as targets to enable specific drug delivery. This is the case with CD44, EGFR, or the folate receptor, among others [ 22 , 226 , 231 , 240 , 241 , 242 , 243 , 244 , 245 ] ( Table 2 ). The only strategy that seems to allow specific binding to the gut epithelium, independently of its physiological or pathological condition, involves WGA.…”

Recent advanced lipid-based nanomedicines for overcoming cancer resistance

“…To increase the accumulation in tumor cells and enhance therapeutic outcomes, liposomes are decorated with surface-attached ligands designed to recognize the specific receptors overexpressed on the surface of various drug-resistant tumor cells. For instance, folate ligands target folate receptor [ 82 - 84 ] , transferrin ligands target transferrin receptor [ 85 , 86 ] , epidermal growth factor (EGF) protein [ 87 ] , epidermal growth factor receptor (EGFR) antibody [ 88 ] , and cetuximab [ 89 , 90 ] target EGFR, and prostate-specific peptide [ 91 ] and prostate-specific antigen gene [ 92 ] target prostate-specific membrane antigen (PSMA). Additionally, single-stranded DNA aptamer [ 93 ] targets forkhead box M1 (FOXM1), biotin [ 94 - 97 ] and fructose [ 96 ] target biotin receptor, and humanized anti-human epidermal growth factor receptor 2 (HER2) antibody [ 98 ] , engineered peptide [ 99 ] , and bispecific antibody [ 100 ] target HER2 receptor.…”

Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery

“…This makes the drug prone to breakdown, reducing its activity. Therefore, a series of CPT prodrugs have been developed in order to improve the solubility and stability of CPT in aqueous solutions, including gemcitabine [ 19 ] and irinotecan [ 20 ], which have already been used in cancer chemotherapy.…”