Nanoparticles of folic acid‐methyl‐β‐cyclodextrin (FA‐MβCD)/adamantane‐albumin exhibit enhanced antitumor activity compared with FA‐MβCD alone

Supramolecular drug carriers are a promising approach for delivering anticancer drugs with high blood retention after administration. We previously synthesized folic acid‐modified methyl‐β‐cyclodextrin (FA‐MβCD) as an anticancer drug. FA‐MβCD has a selective autophagy‐mediated antitumor effect on folic acid receptor (FR)‐expressing cancer cells. Here, we enhanced the antitumor effect and safety of FA‐MβCD by preparing a supramolecular nanoparticle formulation of FA‐MβCD via host–guest interactions using an adamantane conjugate with human serum albumin (Ad‐HSA). The Ad‐HSA/FA‐MβCD supramolecular complex prolonged the blood retention of FA‐MβCD and improved its antitumor effect and safety after intravenous administration in tumor‐bearing mice xenografted with FR‐expressing cancer cells. These results suggest that the supramolecular technique using Ad‐HSA is a promising approach for the delivery of CD‐based anticancer drugs.

[1]  T. Ishida,et al.  Reduction-Responsive and Multidrug Deliverable Albumin Nanoparticles: An Antitumor Drug to Abraxane against Human Pancreatic Tumor-Bearing Mice , 2021 .

[2]  C. Coban,et al.  DAMP-Inducing Adjuvant and PAMP Adjuvants Parallelly Enhance Protective Type-2 and Type-1 Immune Responses to Influenza Split Vaccination , 2018, Front. Immunol..

[3]  T. Higashi,et al.  Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin , 2017, International journal of nanomedicine.

[4]  T. Higashi,et al.  Self-Assembly PEGylation Retaining Activity (SPRA) Technology via a Host-Guest Interaction Surpassing Conventional PEGylation Methods of Proteins. , 2017, Molecular pharmaceutics.

[5]  峻斗 日下部 Intranasal hydroxypropyl-β-cyclodextrin-adjuvanted influenza vaccine protects against sub-heterologous virus infection , 2016 .

[6]  D. Raucher,et al.  Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy , 2015, Molecules.

[7]  R. Kariya,et al.  Evaluation of antitumor effects of folate-conjugated methyl-β-cyclodextrin in melanoma. , 2015, Biological & pharmaceutical bulletin.

[8]  J. Vance,et al.  Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin , 2014, Journal of Lipid Research.

[9]  R. Kariya,et al.  Involvement of Autophagy in Antitumor Activity of Folate-appended Methyl-β-cyclodextrin , 2014, Scientific Reports.

[10]  David Goldstein,et al.  Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. , 2013, The New England journal of medicine.

[11]  T. Higashi,et al.  Potential use of Folate-appended Methyl-β-Cyclodextrin as an Anticancer Agent , 2013, Scientific Reports.

[12]  Jie Zhang,et al.  Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis , 2012, BMC Cancer.

[13]  Francesco M Veronese,et al.  State of the art in PEGylation: the great versatility achieved after forty years of research. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[14]  C. Thompson,et al.  Therapeutic targets in cancer cell metabolism and autophagy , 2012, Nature Biotechnology.

[15]  M. Socinski,et al.  Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  H. Jono,et al.  Cyclodextrin, a novel therapeutic tool for suppressing amyloidogenic transthyretin misfolding in transthyretin-related amyloidosis. , 2011, The Biochemical journal.

[17]  I. Sakaida,et al.  Iron regulation by hepatocytes and free radicals , 2011, Journal of clinical biochemistry and nutrition.

[18]  N. Mizushima,et al.  Methods in Mammalian Autophagy Research , 2010, Cell.

[19]  K. Motoyama,et al.  Involvement of PI3K-Akt-Bad pathway in apoptosis induced by 2,6-di-O-methyl-beta-cyclodextrin, not 2,6-di-O-methyl-alpha-cyclodextrin, through cholesterol depletion from lipid rafts on plasma membranes in cells. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[20]  D. Ory,et al.  Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression , 2009, PloS one.

[21]  J. Repa,et al.  Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1−/− mouse , 2009, Proceedings of the National Academy of Sciences.

[22]  Felix Kratz,et al.  Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[23]  A. Matsukawa,et al.  Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. , 2005, Biochemical pharmacology.

[24]  K. Uekama,et al.  Design and evaluation of cyclodextrin-based drug formulation. , 2004, Chemical & pharmaceutical bulletin.

[25]  T. Tanaka,et al.  Receptor mediated endocytosis and cytotoxicity of transferrin-mitomycin C conjugate in the HepG2 cell and primary cultured rat hepatocyte. , 2001, Biological & pharmaceutical bulletin.

[26]  J. Drevs,et al.  A novel macromolecular prodrug concept exploiting endogenous serum albumin as a drug carrier for cancer chemotherapy. , 2000, Journal of medicinal chemistry.

[27]  C. Leamon,et al.  Folate copolymer-mediated transfection of cultured cells. , 1999, Bioconjugate chemistry.

[28]  F. Pinguet,et al.  Antiproliferative effect of methyl-beta-cyclodextrin in vitro and in human tumour xenografted athymic nude mice. , 1998, British Journal of Cancer.

[29]  F. Hirayama,et al.  Cyclodextrin Drug Carrier Systems. , 1998, Chemical reviews.

[30]  V. Stella,et al.  Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery. , 1996, Journal of pharmaceutical sciences.

[31]  M. Brewster,et al.  Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. , 1996, Journal of pharmaceutical sciences.

[32]  T. Tanaka,et al.  Synthesis of transferrin-mitomycin C conjugate as a receptor-mediated drug targeting system. , 1996, Biological & pharmaceutical bulletin.

[33]  F. Schabel,et al.  Biology and therapeutic response of a mouse mammary adenocarcinoma (16/C) and its potential as a model for surgical adjuvant chemotherapy. , 1978, Cancer treatment reports.

[34]  R. Yumoto,et al.  Enhancing effect of poly(amino acid)s on albumin uptake in human lung epithelial A549 cells. , 2013, Drug metabolism and pharmacokinetics.

[35]  P. Low,et al.  Folate-mediated targeting of therapeutic and imaging agents to cancers. , 1998, Critical reviews in therapeutic drug carrier systems.

[36]  F. Pinguet,et al.  Methyl-β-cyclodextrin in HL-60 parental and multidrug-resistant cancer cell lines: effect on the cytotoxic activity and intracellular accumulation of doxorubicin , 1997, Cancer Chemotherapy and Pharmacology.

[37]  K. Uekama,et al.  Cyclodextrins in drug carrier systems. , 1987, Critical reviews in therapeutic drug carrier systems.