iRGD‐paclitaxel conjugate nanoparticles for targeted paclitaxel delivery

Abstract

Paclitaxel (PTX) is a chemotherapeutic agent which shows antitumor activities against a broad spectrum of cancers. Yet, the current formulation of PTX used in clinic may cause a number of adverse reactions, which significantly limit its application. To obtain better clinical use of PTX, we report, for the first time, iRGD‐PTX conjugate nanoparticles (NPs) for targeted PTX delivery. iRGD‐PTX conjugate was synthesized from thiolated iRGD and 6‐maleimidocaproic acid‐PTX through Michael addition reaction. iRGD‐PTX NPs with hydrodynamic diameter of ~110 nm were self‐assembled from iRGD‐PTX conjugate in deionized water. The as‐prepared iRGD‐PTX NPs exhibit good stability in phosphate buffered saline (PBS) buffer and fetal bovine serum containing PBS buffer. iRGD‐PTX NPs exhibit sustained drug release behaviors. The in vitro studies show that iRGD‐PTX NPs can be internalized by 4T1 cells by integrin αV‐mediated endocytosis, resulting in better in vitro antitumor activity as compared to free PTX. The in vivo studies demonstrate that iRGD‐PTX NPs exhibit enhanced tumor accumulation. The iRGD‐PTX NPs reported here represent a novel PTX nanoplatform to achieve targeted PTX delivery.

High Solubilization and Controlled Release of Paclitaxel Using Thermosponge Nanoparticles for Effective Cancer Therapy

“…The drug release behavior of TNP was determined as previously reported [ 25 , 26 , 27 , 28 ]. A PTX@TNP solution (1 mL, 200 μg of PTX) was added to a Float-A-Lyzer G2 dialysis device (100 kDa MWCO, Spectra/Por Dialysis Membrane, Repligen, Waltham, MA, USA) and then immersed in 10 mL of biological solution (PBS, pH = 7.4) containing 0.5% v / v Tween 80 to determine the sink condition of the drug.…”

Carrier-free nanodrugs for safe and effective cancer treatment

“…Different RGD peptides were also used in the literature. Xu et al reported the conjugation of PTX with iRGD peptide (CRGDKGPDC), forming NPs by dialysis [174]. In another study, Liu et al reported a simple PTX conjugate by using tumor targeting peptide, cyclic Arg-Gly-Asp (cRGDyK), and Ce6, each bonded with HSA separately via amide bonds [175].…”

Construction of protein nanoparticles for targeted delivery of drugs to cancer cells

“…22 Many studies have shown that iRGD enhances the tumor targeting and penetrating ability of conjugated therapeutic agents or nanovehicles. [23][24][25][26] In the present study, iRGD was fused to the C-terminus of ELP-D to have iRGD moieties on the surfaces of protein NPs. We evaluated the anti-cancer effects of paclitaxel (PTX)-loaded protein NPs having iRGD on cancer cells.…”

“…22 Many studies have shown that iRGD enhances the tumor targeting and penetrating ability of conjugated therapeutic agents or nanovehicles. 23–26…”