Highly Biocompatible Functionalized Layer‐by‐Layer Ginger Lipid Nano Vectors Targeting P‐Selectin for Delivery of Doxorubicin to Treat Colon Cancer

Abstract

A biocompatible natural nanoparticle drug delivery system that has specific cancer-targeting function holds vast promise for cancer therapy. Here, a fucoidan/poly-lysine-functionalized layer-by-layer ginger-derived lipid vector (LbL-GDLV) is designed to target P-selectin and deliver a loaded drug into vascularized colon cancer. LbL-GDLVs selectively bound to P-selectin, and the degradation of the fucoidan result in rapid attachment of the cancer cell and internalization of the remaining positively charged poly-lysine coated-GDLVs. Upon enzymolysis of the poly-lysine layer inside the cancer cell, the GDLV core releases loaded doxorubicin (Dox) which has the expected effects. Bio-distribution studies show that intravenously injected LbL-GDLVs exhibit enhanced accumulation at the vascularized tumor site (≈4.4-fold higher than control), presumably due to P-selectin-mediated targeting plus the enhanced permeability and retention effect (EPR). In two animal models (Luc-HT-29 and HCT-116 xenografts), Dox-loaded LbL-GDLVs (LbL-GDLVs/Dox) significantly inhibit tumor growth and demonstrate much better therapeutic efficiency than free Dox. More importantly, LbL-GDLVs exhibit excellent biocompatibility, and LbL-GDLVs encapsulation largely reduces the cardiotoxicity of free Dox and avoids the notorious drug resistance of colon cells against free Dox. Together, these findings demonstrate the potential of our newly designed and highly biocompatible plant-derived LbL nanoparticles and their precise colon cancer drug delivery function.

Low pH-Based Method to Increase the Yield of Plant-Derived Nanoparticles from Fresh Ginger Rhizomes

“…10 Ginger PDNP-derived nano vectors have also been employed for the targeted delivery of cargos to cancer cells in vivo, via coencapsulating cancer-targeting ligands such as folic acid (FA), highlighting the potential of ginger PDNPs as a cost-effective nanocarrier. 11,12 MicroRNAs (miRNAs) are small, endogenously derived 18−25 nt RNAs which regulate target mRNAs by translational repression and/or transcript degradation. Three independent studies have shown the presence of miRNAs in ginger PDNPs with potential therapeutic benefits.…”

“…Similarly, ginger PDNP-derived lipids were used as nanocarriers for oral delivery of siRNA against divalent metal-ion transporter (Dmt1) to treat hereditary hemochromatosis . Ginger PDNP-derived nano vectors have also been employed for the targeted delivery of cargos to cancer cells in vivo , via co-encapsulating cancer-targeting ligands such as folic acid (FA), highlighting the potential of ginger PDNPs as a cost-effective nanocarrier. , …”

Orally Administrable Therapeutic Nanoparticles for the Treatment of Colorectal Cancer

“…Plant-derived natural NPs are used to overcome off-target cytotoxicity and high cost of mass production of traditional NPs. Nanocarriers derived from edible plants, such as ginger, grapefruit, broccoli, and lemon, can be used for drug delivery ( Wang et al, 2013 ; Zhang et al, 2016a , b ; Yang et al, 2018 ; Zhang M. et al, 2019 ). These nanocarriers have exosomal-like traits and can be applied in exosome-based drug delivery systems.…”

All-in-one theranostic nano-platform based on polymer nanoparticles for BRET/FRET-initiated bioluminescence imaging and synergistically anti-inflammatory therapy for ulcerative colitis

“…P-selectin is a membrane glycoprotein expressed on vascular endothelial cells in most tissues, and is a member of the selectin family that mediates cell rolling and platelet adhesion. It plays an important role in the accumulation of white blood cells towards the damaged site in the early stage of inflammation [ 45 – 48 ]. Notably, elevated P-selectin expression was found in inflammatory sites of the ulcerative colon but not healthy tissues in humans and mice, suggesting that P-selectin may be a specific target for delivery of nanomedicine to the colon in the treatment of UC.…”