<p>Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tumor Effects Of Paclitaxel-Loaded PLGA Nanoparticles For Colorectal Cancer Treatment</p>

Abstract

BackgroundNanoparticles exhibit great promise for improving the solubility and tissue-specific distribution of chemotherapeutic agents; however, the passive and highly variable enhanced permeability and retention (EPR) effects observed in tumors frequently leads to insufficient delivery of nanodrugs into tumors. The tumor-penetrating peptide iRGD can actively enhance tumor-selective delivery of nanoparticles into tumors by binding to integrin and interacting with tissue-penetrating receptor neuropilin-1.Materials and methodsTo improve colorectal cancer treatment, in this study, we prepared a paclitaxel (PTX)-loaded PLGA nanoparticle (PLGA-PTX) and evaluated its tumor-targeting and antitumor activity by co-administration with iRGD.ResultsCompared to free PTX, encapsulated PTX retained preferential cytotoxicity toward various colorectal cancer cells while effectively sparing healthy cells. PLGA-PTX treatment resulted in cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of cancer cell migration and invasion. PLGA-PTX combined with iRGD displayed little enhancement of cytotoxicity in vitro. Despite this, iRGD receptors integrin and neuropilin-1 were found to be primarily overexpressed on abundant tumor vessels in mice bearing colorectal tumors. Consequently, co-administration of nanoparticles with iRGD promoted the selective delivery of nanoparticles into tumor tissues in vivo. Additionally, the combined regimen enhanced the antitumor effects compared to those of each individual reagent.ConclusionOur findings suggest that PLGA nanoparticles combined with the iRGD peptide provide a promising drug delivery strategy for facilitating active drug accumulation into tumors, given that iRGD receptors are overexpressed on tumor vessels. This co-administration system lacking covalent conjugation provides a more convenient means to combine various therapeutic agents with iRGD to achieve personalized nanotherapy.

Co-Administration of iRGD with Sorafenib-Loaded Iron-Based Metal-Organic Framework as a Targeted Ferroptosis Agent for Liver Cancer Therapy

“…Next, the HepG2 cells were incubated with DMEM, MIL-101(Fe)@sor NPs, and MIL-101(Fe)@sor NPs + iRGD for 6 h (using 10 μM Sor and 30 μmol/L iRGD). 24 Then the cells were collected, washed with PBS three times, centrifuged, and uniformly dispersed in agarose gel. Finally, the cells were scanned with 3.0 T MR, and the T2* mapping image signals were reconstructed using a GE AW 4.6 Advantage Workstation.…”

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

“…Some studies investigated whether the co-administration of iRGD with drug delivery systems can improve chemotherapeutic efficacy. For example, Zhong et al showed that the co-administration of iRGD with the paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle facilitates drug accumulation in tumors, and improves the antitumor effects when compared with the paclitaxel-loaded PLGA without iRGD co-administration [ 129 ]. The co-administration of iRGD with irinotecan-loaded silicasome was also reported to activate the NRP-1-mediated transcytosis transport pathway in pancreatic ductal adenocarcinoma, supporting the notion that iRGD can improve the efficacy of irinotecan-based silicasome [ 131 ].…”

<p>A Review of Biomimetic Nanoparticle Drug Delivery Systems Based on Cell Membranes</p>

“…Poly (lactic-co-glycolic acid) (PLGA) has been one of the most studied polymeric carriers approved by the FDA for anticancer therapy because of its low systemic toxicity and high biodegradability compared to other polymeric systems. 7 As a controlled-release formulation of drugs, 8 drug molecules in NPs are slowly released from the pores of the material surface as the PLGA degrades, as a result, the drugs maintain a constant concentration for a long time, prolong the exposure time, and improve the bioavailability. 9 What is more, another attractive characteristic of PLGA over other nanoparticles is that PLGA is one of the best characterized biodegradable copolymers because it decomposes into nontoxic lactic acid and glycolic acid and further into H 2 O and CO 2 eliminated from the body with low to no toxicity.…”