Beta-lapachone-containing PEG-PLA Polymer Micelles As Novel Nanotherapeutics Against NQO1-overexpressing Tumor Cells

Overview

Journal J Control Release

Specialty Pharmacology

Date 2007 Jun 19

PMID 17574288

Citations 43

Authors

Elvin Blanco

Erik A Bey

Ying Dong

Brent D Weinberg

Damon M Sutton

David A Boothman

Jinming Gao

Affiliations

Soon will be listed here.

Abstract

Beta-lapachone (beta-lap) is a novel anticancer agent that is bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in a variety of tumors. Despite its therapeutic promise, the poor aqueous solubility of beta-lap hinders its preclinical evaluation and clinical translation. Our objective was to develop beta-lap-containing poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PLA) polymer micelles for the treatment of NQO1-overexpressing tumors. Several micelle fabrication strategies were examined to maximize drug loading. A film sonication method yielded beta-lap micelles with relatively high loading density (4.7+/-1.0% to 6.5+/-1.0%) and optimal size (29.6+/-1.5 nm). Release studies in phosphate-buffered saline (pH 7.4) showed the time (t(1/2)) for 50% of drug release at 18 h. In vitro cytotoxicity assays were performed in NQO1-overexpressing (NQO1+) and NQO1-null (NQO1-) H596 lung, DU-145 prostate, and MDA-MB-231 breast cancer cells. Cytotoxicity data showed that after a 2 h incubation with beta-lap micelles, a marked increase in toxicity was shown in NQO1+ cells over NQO1- cells, resembling free drug both in efficacy and mechanism of cell death. In summary, these data demonstrate the potential of beta-lap micelles as an effective therapeutic strategy against NQO1-overexpressing tumor cells.

Citing Articles

Elucidation of Protonation Cooperativity of a STING-Activating Polymer.

Wang M, Bennett Z, Singh P, Feng Q, Wilhelm J, Huang G Adv Mater. 2023; 35(51):e2305255.

PMID: 37541432 PMC: 10838353. DOI: 10.1002/adma.202305255.

Chemopreventive Potential of Dietary Nanonutraceuticals for Prostate Cancer: An Extensive Review.

Chopra H, Bibi S, Goyal R, Gautam R, Trivedi R, Upadhyay T Front Oncol. 2022; 12:925379.

PMID: 35903701 PMC: 9315356. DOI: 10.3389/fonc.2022.925379.

Review on NAD(P)H dehydrogenase quinone 1 (NQO1) pathway.

Preethi S, Arthiga K, Patil A, Spandana A, Jain V Mol Biol Rep. 2022; 49(9):8907-8924.

PMID: 35347544 DOI: 10.1007/s11033-022-07369-2.

Self-Assembled Amphiphilic Fluorinated Random Copolymers for the Encapsulation and Release of the Hydrophobic Combretastatin A-4 Drug.

Calosi M, Guazzelli E, Braccini S, Lessi M, Bellina F, Galli G Polymers (Basel). 2022; 14(4).

PMID: 35215686 PMC: 8880340. DOI: 10.3390/polym14040774.

Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis.

Zhou Y, Yan H, Zhou Q, Feng R, Wang P, Yang F Front Pharmacol. 2021; 12:766909.

PMID: 34790130 PMC: 8591123. DOI: 10.3389/fphar.2021.766909.

References

Jones M, Leroux J . Polymeric micelles - a new generation of colloidal drug carriers. Eur J Pharm Biopharm. 1999; 48(2):101-11. DOI: 10.1016/s0939-6411(99)00039-9. View

Quellec P, Gref R, Dellacherie E, Sommer F, Tran M, Alonso M . Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II. Controlled release properties. J Biomed Mater Res. 1999; 47(3):388-95. DOI: 10.1002/(sici)1097-4636(19991205)47:3<388::aid-jbm14>3.0.co;2-v. View

Pink J, Planchon S, Tagliarino C, Varnes M, Siegel D, Boothman D . NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity. J Biol Chem. 2000; 275(8):5416-24. DOI: 10.1074/jbc.275.8.5416. View

Hashizume H, Baluk P, Morikawa S, McLean J, Thurston G, Roberge S . Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000; 156(4):1363-80. PMC: 1876882. DOI: 10.1016/S0002-9440(10)65006-7. View

Gref , Luck , Quellec , MARCHAND , Dellacherie , HARNISCH . 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces. 2000; 18(3-4):301-313. DOI: 10.1016/s0927-7765(99)00156-3. View

Siegel D, Ross D . Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues. Free Radic Biol Med. 2000; 29(3-4):246-53. DOI: 10.1016/s0891-5849(00)00310-5. View

Gref R, Quellec P, Sanchez A, Calvo P, Dellacherie E, Alonso M . Development and characterization of CyA-loaded poly(lactic acid)-poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers. Eur J Pharm Biopharm. 2001; 51(2):111-8. DOI: 10.1016/s0939-6411(00)00143-0. View

Tagliarino C, Pink J, Dubyak G, Nieminen A, Boothman D . Calcium is a key signaling molecule in beta-lapachone-mediated cell death. J Biol Chem. 2001; 276(22):19150-9. DOI: 10.1074/jbc.M100730200. View

Maeda H . The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001; 41:189-207. DOI: 10.1016/s0065-2571(00)00013-3. View

10.

Yamamoto Y, Nagasaki Y, Kato Y, Sugiyama Y, Kataoka K . Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge. J Control Release. 2001; 77(1-2):27-38. DOI: 10.1016/s0168-3659(01)00451-5. View

11.

Ulbrich K, Etrych T, Chytil P, Jelinkova M, Rihova B . HPMA copolymers with pH-controlled release of doxorubicin: in vitro cytotoxicity and in vivo antitumor activity. J Control Release. 2003; 87(1-3):33-47. DOI: 10.1016/s0168-3659(02)00348-6. View

12.

Otsuka H, Nagasaki Y, Kataoka K . PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev. 2003; 55(3):403-19. DOI: 10.1016/s0169-409x(02)00226-0. View

13.

Savic R, Luo L, Eisenberg A, Maysinger D . Micellar nanocontainers distribute to defined cytoplasmic organelles. Science. 2003; 300(5619):615-8. DOI: 10.1126/science.1078192. View

14.

Torchilin V, Lukyanov A, Gao Z, Papahadjopoulos-Sternberg B . Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci U S A. 2003; 100(10):6039-44. PMC: 156322. DOI: 10.1073/pnas.0931428100. View

15.

Logsdon C, Simeone D, Binkley C, Arumugam T, Greenson J, Giordano T . Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res. 2003; 63(10):2649-57. View

16.

Tagliarino C, Pink J, Reinicke K, Simmers S, Wuerzberger-Davis S, Boothman D . Mu-calpain activation in beta-lapachone-mediated apoptosis. Cancer Biol Ther. 2003; 2(2):141-52. DOI: 10.4161/cbt.2.2.237. View

17.

Higuchi T . MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. J Pharm Sci. 1963; 52:1145-9. DOI: 10.1002/jps.2600521210. View

18.

Nasongkla N, Wiedmann A, Bruening A, Beman M, Ray D, Bornmann W . Enhancement of solubility and bioavailability of beta-lapachone using cyclodextrin inclusion complexes. Pharm Res. 2003; 20(10):1626-33. DOI: 10.1023/a:1026143519395. View

19.

Panduri V, Weitzman S, Chandel N, Kamp D . Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis. Am J Physiol Lung Cell Mol Physiol. 2004; 286(6):L1220-7. DOI: 10.1152/ajplung.00371.2003. View

20.

Kim T, Kim D, Chung J, Shin S, Kim S, Heo D . Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004; 10(11):3708-16. DOI: 10.1158/1078-0432.CCR-03-0655. View