Multi-functional nanocomplex codelivery of Trp2 and R837 to activate melanoma-specific immunity.

Abstract

Antigen-adjuvant combination could induce a protective and long-lasting anti-tumor immune response. However, exploiting system which could co-deliver melanoma antigen peptide Trp2 (Tyrosinase-related protein 2) and Toll-like-receptor-7 (TLR7) agonists imiquimod (R837) both are poor aqueous solubility is still challenging. Our new nanocomplex was explored for specific delivery of Trp2 and R837 into antigen-presenting cells (APCs). R837 was loaded into mannosylated-β-cyclodextrin (Man-CD) to target dendritic cells (DCs) by binding mannose receptors (MR) on DCs. A fusion peptide (WT) was constructed by incorporating the amino acid region of TAT (cell-penetrating peptide) into Trp2 to improve the TAT-mediated intracellular efficiency. Negatively charged sodium alginate (SA), a biocompatible polymer, which can induce adjuvant responses by affecting the functions of DCs, was complexed with Man-CD/R837 and WT via physical adsorption. The optimized nanocomplex promoted the cellular uptake and showed remarkable efficacy to enhance the secreting of Th1-cytokines. This multi-functional nanocomplex system may allow effective targeting-codelivery of multi-hydrophobic drugs and be a promising subunit vaccine candidate as a potential prevention action of tumor.

• Authors: Zhonghua Ji, Zeng Tan, Min Li, Jin Tao, Enshuang Guan, Junrong Du, Ying Hu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 582 Pg. 119310 (May 30 2020) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 32276088 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Alginates
• Cancer Vaccines
• Cytokines
• Drug Carriers
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Membrane Proteins
• Peptide Fragments
• Receptors, Cell Surface
• beta-Cyclodextrins
• peptide SVYDFFVWL
• Imiquimod
• Mannose

Topics

• Adjuvants, Immunologic (administration & dosage, chemistry, pharmacology)
• Alginates (chemistry, pharmacology)
• Animals
• Cancer Vaccines (administration & dosage, chemistry, pharmacology)
• Cell Line, Tumor
• Cytokines (metabolism)
• Dendritic Cells (drug effects, metabolism)
• Drug Carriers
• Drug Compounding
• Female
• Hydrophobic and Hydrophilic Interactions
• Imiquimod (administration & dosage, chemistry, pharmacology)
• Lectins, C-Type (metabolism)
• Mannose (chemistry)
• Mannose Receptor
• Mannose-Binding Lectins (metabolism)
• Melanoma, Experimental (drug therapy, immunology, metabolism)
• Membrane Proteins (administration & dosage, chemistry, pharmacology)
• Mice, Inbred C57BL
• Nanoparticles
• Peptide Fragments (administration & dosage, chemistry, pharmacology)
• Receptors, Cell Surface (metabolism)
• Solubility
• T-Lymphocytes, Helper-Inducer (drug effects, metabolism)
• beta-Cyclodextrins (chemistry)