A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

Abstract

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Orally administrable polyphenol-based nanoparticles achieve anti-inflammation and antitumor treatment of colon diseases

“…[7][8][9][10] In this regard, great efforts have been made on nanoparticulate drug delivery systems to optimize physicochemical parameters and thus improve drug delivery efficiency of nanocarriers. [11][12][13][14][15][16] Some nanocarriers have exhibited many advantages for oral drug delivery owing to their improved stability, prolonged drug residence time and high mucus-penetrating ability in the GI tract. 11,[17][18][19][20][21][22] Besides, various pH-, ligand/receptor-, charge-, and bacteria-mediated targeted drug delivery systems have been applied to improve the therapeutic outcomes of colon diseases.…”

Local Administration of Ginkgolide B Using a Hyaluronan-Based Hydrogel Improves Wound Healing in Diabetic Mice

“…The scratch experiment was performed as previously described ( Sun, 2021 ). Briefly, L929 and HUVEC at a density of 4 × 10 5 cells/well were cultured within 6-well plates, respectively.…”

Multifunctional co-transport carriers based on cyclodextrin assembly for cancer synergistic therapy

“…It was observed that the resulting nanocomposite could be taken up by the cells, and it showed the effect of enhanced the secretion of Th1 cytokines. In another study, folic acid targeting polyethylene glycol modified amphiphilic β-CD nanoparticles were shown to assemble ginsenoside Rg3 and quercetin 91 . This co-delivery system could improve drug delivery barrier in the body.…”