Doxorubicin-Loaded CuS Nanoparticles Conjugated with GFLG: A Novel Drug Delivery System for Lymphoma Treatment

Abstract

Doxorubicin (DOX) plays an important part in lymphoma treatment. However, various side e®ects on normal tissues restrict its clinical use. Nanocarriers connected by Gly-Phe-Leu-Gly (GFLG) can be equipped with the advantages of nanoparticles (NPs), their enhanced permeability and retention (EPR) e®ect, and surface modi¯ability. Nanocarriers can also be speci¯cally enzymatically hydrolyzed by cathepsin (Cath) B, a kind of enzyme highly expressed in tumor cells. In this work, we proposed a novel drug delivery system comprising GFLG conjugated with copper sul¯de (CuS) NPs loaded with DOX. The system, designated as CuS-GFLG-DOX, could be used for NP-based targeted combination chemotherapy. Results showed that the drug delivery system had an appropriate diameter, good dispersibility, high encapsulation e±ciency and high drug loading. The system also exhibited an excellent targeting of lymphoma cells and an enhanced antitumor activity. The possible pathway to induce cytotoxic e®ects was Bcl-2/caspasemediated apoptosis pathway. In conclusion, CuS-GFLG-DOX could precisely deliver drugs to lymphoma cells and could be a novel and promising therapeutic option for lymphoma.

Peptide-Based Drug Delivery Systems

“…Tumor environment-responsiveness of GFLG was also utilized by Jiang and colleagues who used DOX as a drug of interest, which has only 5% bioavailability after oral administration [102]. DOX is the most well-known anthracycline antibiotic that has been successfully used as an anti-cancer drug to treat hematological and solid tumor malignancies for more than 40 years [103].…”

“…Intracellular in vitro accumulation studies showed almost two-fold higher relative fluorescence intensities for CuS-GFLG-DOX in comparison to free DOX. The proposed DDS also generated an enhanced apoptosis rate in Raji cell lines compared to the control [102]. Wang and colleagues also used a GFLG-conjugated DDS to deliver DOX.…”

In vitro evaluation of copper sulfide nanoparticles decorated with folic acid/chitosan as a novel pH‐sensitive nanocarrier for the efficient controlled targeted delivery of cytarabine as an anticancer drug

“…Various techniques, such as nanotubes, 18 nanowires, 19 and NPs, 20 have been used to produce CuS NPs. In fact, CuS NPs have the advantages of relatively high yield, small size, low cytotoxicity, low production cost, and good biocompatibility 21 . CuS NPs make them appropriate for numerous applications in catalysis, 22 molecular imaging, 23 photothermal therapy, 24–26 drug delivery, 27 electrodes, 28 etc.…”

“…In fact, CuS NPs have the advantages of relatively high yield, small size, low cytotoxicity, low production cost, and good biocompatibility. 21 CuS NPs make them appropriate for numerous applications in catalysis, 22 molecular imaging, 23 photothermal therapy, [24][25][26] drug delivery, 27 electrodes, 28 etc. In addition to the increased single-therapy threshold by the delivery system, to obtain an optimized anticancer influence, CuS NPs can act as specific radiosensitizers.…”