Cyclodextrin-based Host-guest Complexes Loaded with Regorafenib for Colorectal Cancer Treatment

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Feb 4

PMID 33536421

Citations 33

Authors

Hongzhen Bai

Jianwei Wang

Chi Uyen Phan

Qi Chen

Xiurong Hu

Guoqiang Shao

Jun Zhou

Lihua Lai

Guping Tang

Affiliations

Soon will be listed here.

Abstract

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

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References

Yu G, Jie K, Huang F . Supramolecular Amphiphiles Based on Host-Guest Molecular Recognition Motifs. Chem Rev. 2015; 115(15):7240-303. DOI: 10.1021/cr5005315. View

Yu H, Pardoll D, Jove R . STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009; 9(11):798-809. PMC: 4856025. DOI: 10.1038/nrc2734. View

Neufert C, Becker C, Neurath M . An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression. Nat Protoc. 2007; 2(8):1998-2004. DOI: 10.1038/nprot.2007.279. View

Huang H, Tang G, Wang Q, Li D, Shen F, Zhou J . Two novel non-viral gene delivery vectors: low molecular weight polyethylenimine cross-linked by (2-hydroxypropyl)-beta-cyclodextrin or (2-hydroxypropyl)-gamma-cyclodextrin. Chem Commun (Camb). 2006; (22):2382-4. DOI: 10.1039/b601130f. View

Schluep T, Cheng J, Khin K, Davis M . Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemother Pharmacol. 2005; 57(5):654-62. DOI: 10.1007/s00280-005-0091-7. View

Ferrari M . Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005; 5(3):161-71. DOI: 10.1038/nrc1566. View

Clevers H . At the crossroads of inflammation and cancer. Cell. 2004; 118(6):671-4. DOI: 10.1016/j.cell.2004.09.005. View

Uekama K, Hirayama F, Irie T . Cyclodextrin Drug Carrier Systems. Chem Rev. 2002; 98(5):2045-2076. DOI: 10.1021/cr970025p. View

Waddell T, Cunningham D . Evaluation of regorafenib in colorectal cancer and GIST. Lancet. 2012; 381(9863):273-5. DOI: 10.1016/S0140-6736(12)62006-6. View

10.

Yongvongsoontorn N, Chung J, Gao S, Bae K, Yamashita A, Tan M . Carrier-Enhanced Anticancer Efficacy of Sunitinib-Loaded Green Tea-Based Micellar Nanocomplex beyond Tumor-Targeted Delivery. ACS Nano. 2019; 13(7):7591-7602. DOI: 10.1021/acsnano.9b00467. View

11.

Ryan A, Colleran A, OGorman A, OFlynn L, Pindjacova J, Lohan P . Targeting colon cancer cell NF-κB promotes an anti-tumour M1-like macrophage phenotype and inhibits peritoneal metastasis. Oncogene. 2014; 34(12):1563-74. DOI: 10.1038/onc.2014.86. View

12.

Cheng J, Khin K, Davis M . Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates. Mol Pharm. 2005; 1(3):183-93. DOI: 10.1021/mp049966y. View

13.

Gilbert L, Hemann M . DNA damage-mediated induction of a chemoresistant niche. Cell. 2010; 143(3):355-66. PMC: 2972353. DOI: 10.1016/j.cell.2010.09.043. View

14.

Isidro R, Appleyard C . Colonic macrophage polarization in homeostasis, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol. 2016; 311(1):G59-73. PMC: 4967174. DOI: 10.1152/ajpgi.00123.2016. View

15.

De Mattia E, Cecchin E, Toffoli G . Pharmacogenomics of intrinsic and acquired pharmacoresistance in colorectal cancer: Toward targeted personalized therapy. Drug Resist Updat. 2015; 20:39-70. DOI: 10.1016/j.drup.2015.05.003. View

16.

Iacovelli R, Palazzo A, Procopio G, Santoni M, Trenta P, De Benedetto A . Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy. Br J Clin Pharmacol. 2013; 77(6):929-38. PMC: 4093918. DOI: 10.1111/bcp.12231. View

17.

Miller K, Siegel R, Lin C, Mariotto A, Kramer J, Rowland J . Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016; 66(4):271-89. DOI: 10.3322/caac.21349. View

18.

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

19.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

20.

Davis M, Brewster M . Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004; 3(12):1023-35. DOI: 10.1038/nrd1576. View