A CD326 monoclonal antibody modified core cross-linked curcumin-polyphosphoester prodrug for targeted delivery and cancer treatment

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 11; no. 39; pp. 9467 - 9477
• Main Authors: Li, Haijiao, Zhang, Mingzu, He, Jinlin, Liu, Jian, Sun, Xingwei, Ni, Peihong
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 11.10.2023
• Subjects: Addition polymerization; Antitumor agents; Biomedical materials; Blood circulation; Body fluids; Cancer; Cancer therapies; Crosslinking; Curcumin; Disulfide bonds; Drug delivery; Drug delivery systems; Drug development; Glutathione; Hydrophobicity; In vitro methods and tests; Micelles; Monoclonal antibodies; Nanoparticles; NMR; Nuclear magnetic resonance; Organic solvents; Polymers; Ring opening; Stimuli; Structural stability; Tumor cells; Tumor microenvironment; Tumor suppression; Tumors
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d3tb01703f

Stimuli-responsive cross-linked micelles (SCMs) are ideal nanocarriers for anti-cancer drugs. Compared with non-cross-linked micelles, SCMs exhibit superior structural stability. At the same time, the introduction of an environmentally sensitive crosslinker into a drug delivery system allows SCMs to respond to single or multiple stimuli in the tumor microenvironment, which can minimize drug leakage during the blood circulation process. In this study, curcumin (CUR) was modified as the hydrophobic core crosslinker by utilizing the bisphenol structure, and redox sensitive disulfide bonds were introduced to prepare the glutathione (GSH) stimulated responsive core crosslinker (abbreviated as N 3 - ss -CUR- ss -N 3 ). In addition, amphiphilic polymer APEG- b -PBYP was prepared through the ring opening reaction, and reacted with the crosslinker through the "click" reaction. After being dispersed in the aqueous phase, core cross-linked nanoparticles (CCL NPs) were obtained. Finally, monoclonal antibody CD326 (mAb-CD326) was reduced and coupled to the hydrophilic chain ends to obtain the nanoparticles with surface modified antibodies (R-mAb-CD326@CCL NPs) for further enhancing targeted drug delivery. The structures of the polymer and crosslinker were characterized by 1 H NMR, UV-Vis, FT-IR, and GPC. The morphology, size and stability of CCL NPs and R-mAb-CD326@CCL NPs were investigated by DLS and TEM. The in vitro drug release behavior of CCL NPs was also studied. The results showed that the CCL NPs exhibited reduction-responsiveness and were able to release the original drug CUR under 10 mM GSH conditions. Additionally, the CCL NPs exhibited excellent stability in both the simulated body fluid environment and organic solvents. Especially, R-mAb-CD326@CCL NPs can actively target tumor cells and showed better therapeutic efficacy in in vivo experiments with a tumor suppression rate of 78.7%. This work provides a new idea for the design of nano-drugs targeting breast cancer. A new type of nanodrug with curcumin derivatives as the crosslinker, which can maintain stability in blood circulation and actively target breast cancer tumors.