Folate-polyethylene glycol conjugated carboxymethyl chitosan for tumor-targeted delivery of 5-fluorouracil

Abstract

Targeted drug delivery has been evolving at an increasing rate due to its potential to reduce the minimum effective dose of a drug and its accompanying side effects. It has shown improved therapeutic efficacy at equivalent plasma concentrations; however, the development of effective targeted delivery systems has remained a major task. In this study, a drug carrier was designed and synthesized by conjugation of folate acid (FA) to carboxymethyl chitosan (CMCS) through a polyethylene glycol (PEG) spacer. The resulting conjugates were confirmed by 1H nuclear magnetic resonance and infrared spectroscopy. The cytotoxicity of CMCS and CMCS‑5‑fluorouracil (5‑FU) was determined by a crystal violet stain assay. The potential of CMCS‑PEG‑FA for use in the targeted delivery of 5‑FU was investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide analysis in two cell lines, HeLa and A549, which contain different numbers of folate receptors on their surfaces. The MTT results revealed that in HeLa cells, the cytotoxicity of (CMCS‑5‑FU)‑PEG‑FU cells is greater compared with CMCS‑5‑FU, suggesting that folate receptor‑mediated endocytosis may affect the cellular uptake efficiency of 5‑FU‑loaded CMCS‑PEG‑FA. The CMCS‑PEG‑FA conjugates presented in this study show promise as carriers for chemotherapeutic agents due to their solubility at physiological pH, efficiency in carrying chemotherapeutic agents, low cytotoxicity and targeting ability.

Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil

“…Consequently, an active methylene group was introduced in the scaffold of 5-FU, which served as a linker among 5-FU and PEG amino units. UV-Vis, FTIR, and 1 HNMR (see Supplementary Materials) characterization demonstrated the synthesis of prodrug (FA-PEG-5-FU) with desired purity and was also consistent with previously designed folate-based drug delivery carriers [26,55]. Figure 1 indicates that FA is linked to PEG-bisamine for the slow release of 5-FU.…”

Nd3+ sensitized core-shell-shell nanocomposites loaded with IR806 dye for photothermal therapy and up-conversion luminescence imaging by a single wavelength NIR light irradiation

“…Further loading of the photosensitizer IR806 (20 wt%) in the pores and coating with positively charged PAH containing NH 2 functional groups to prevent the loss of IR806 79 , the zeta potential of the resulted UCNP@mSiO 2 /IR806@PAH was +81.2 mV. If the FA-PEG-NHS ester was covalently bonded to the nanoparticles via peptide bond formation with the NH 2 functional groups for active tumor targeting 80 , the zeta potential of the final UCNP@mSiO 2 /IR806 @PAH/PEG-FA nanocomposite was +65.3 mv. Using this nanocomposite at concentrations from 3.9 to 62.5 µg/mL, the dark cell viabilities were all greater than 85%, indicating that this material was rather safe for further biological and preclinical tests ( vide infra ).…”

Synthesis of folate-chitosan nanoparticles loaded with ligustrazine to target folate receptor positive cancer cells

“…Folate is a stable, inexpensive and poorly immunogenic chemical with a high affinity for FR ( 16 ). FA-CS-NPs have been loaded with anticancer agents, such as doxorubicin ( 17 ), 5-fluorouracil ( 18 ) and used as DNA ( 19 ) delivery vehicle, in previous studies. LZ has been reported to have anticoagulation, antioxidation and calcium antagonism properties, thus, is widely used in the management of cardiovascular and cerebrovascular diseases ( 20 ).…”