Enzyme-triggered nanomedicine: Drug release strategies in cancer therapy (Invited Review)

References

• Abe T, Sakamoto K, Kamohara H, Hirano Y, Kuwahara N, Ogawa M. 1997. Group II phospholipase A2 is increased in peritoneal and pleural effusions in patients with various types of cancer. Int J Cancer 74:245–250.
   PubMed Web of Science ®Google Scholar
• Allen TM, Brandeis E, Hansen CB, Kao GY, Zalipsky S. 1995. A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. Biochim Biophys Acta 1237:99–108.
   PubMed Web of Science ®Google Scholar
• Altucci L, Gronemeyer H. 2001. The promise of retinoids to fight against cancer. Nat Rev Cancer 1:181–193.
   PubMed Web of Science ®Google Scholar
• Andresen TL, Davidsen J, Begtrup M, Mouritsen OG, Jorgensen K. 2004a. Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugs. J Med Chem 47:1694–1703.
   PubMed Web of Science ®Google Scholar
• Andresen TL, Jensen SS, Jorgensen K. 2005a. Advanced strategies in liposomal cancer therapy: Problems and prospects of active and tumor specific drug release. Prog Lipid Res 44:68–97.
   PubMed Web of Science ®Google Scholar
• Andresen TL, Jensen SS, Madsen R, Jorgensen K. 2005b. Synthesis and biological activity of anticancer ether lipids that are specifically released by phospholipase A(2) in tumor tissue. J Med Chem 48:7305–7314.
   PubMed Web of Science ®Google Scholar
• Andresen TL, Mouritsen OG, Begtrup M, Jorgensen K. 2002. Phospholipase A2 activity: Dependence on liposome surface charge and polymer coverage. Biophys J 82:148A.
   Web of Science ®Google Scholar
• Andresen TL, Skytte DM, Madsen R. 2004b. Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis. Org Biomol Chem 2:2951–2957.
   PubMedGoogle Scholar
• Banerjee J, Hanson AJ, Gadam B, Elegbede AI, Tobwala S, Ganguly B, Wagh AV, Muhonen WW, Law B, Shabb JB, Srivastava DK, Mallik S. 2009. Release of liposomal contents by cell-secreted matrix metalloproteinase-9. Bioconjugate Chem 20:1332–1339.
   PubMed Web of Science ®Google Scholar
• Barenholz Y. 2001. Liposome application: problems and prospects. Curr Opin Colloid Interface Sci 6:66–77.
   Web of Science ®Google Scholar
• Berg OG, Gelb MH, Tsai MD, Jain MK. 2001. Interfacial enzymology: the secreted phospholipase A(2)-paradigm. Chem Rev 101:2613–2654.
   PubMed Web of Science ®Google Scholar
• Berkovic D. 1998. Cytotoxic etherphospholipid analogues. Gen Pharmacol 31:511–517.
   PubMedGoogle Scholar
• Bisby RH, Mead C, Morgan CG. 2000. Active uptake of drugs into photosensitive liposomes and rapid release on UV photolysis. Photochem Photobiol 72:57–61.
   PubMed Web of Science ®Google Scholar
• Brachwitz H, Vollgraf C. 1995. Analogs of alkyllysophospholipids: chemistry, effects on the molecular level and their consequences for normal and malignant cells. Pharmacol Ther 66:39–82.
   PubMed Web of Science ®Google Scholar
• Briknarova K, Gehrmann M, Banyai L, Tordai H, Patthy L, Llinas M. 2001. Gelatin-binding region of human matrix metalloproteinase-2 – Solution structure, dynamics, and function of the COL-23 two-domain construct. J Biol Chem 276:27613–27621.
   PubMedGoogle Scholar
• Cheong I, Huang X, Bettegowda C, Diaz LA, Kinzler KW, Zhou SB, Vogelstein B. 2006. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314:1308–1311.
   PubMed Web of Science ®Google Scholar
• Cheong I, Huang X, Thornton K, Diaz LA, Zhou SB. 2007. Targeting cancer with bugs and liposomes: ready, aim, fire. Cancer Res 67:9605–9608.
   PubMed Web of Science ®Google Scholar
• Collins D, Litzinger DC, Huang L. 1990. Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols. Biochim Biophys Acta 1025:234–242.
   PubMed Web of Science ®Google Scholar
• Connor J, Yatvin MB, Huang L. 1984. pH-sensitive liposomes: acid-induced liposome fusion. Proc Natl Acad Sci USA 81:1715–1718.
   PubMed Web of Science ®Google Scholar
• Davidsen J, Jorgensen K, Andresen TL, Mouritsen OG. 2003. Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue. Biochim Biophys Acta 1609:95–101.
   PubMed Web of Science ®Google Scholar
• Davis SC, Szoka FC. 1998. Cholesterol phosphate derivatives: synthesis and incorporation into a phosphatase and calcium-sensitive triggered release liposome. Bioconjugate Chem 9:783–92.
   PubMed Web of Science ®Google Scholar
• Drummond DC, Zignani M, Leroux J. 2000. Current status of pH-sensitive liposomes in drug delivery. Prog Lipid Res 39:409–460.
   PubMed Web of Science ®Google Scholar
• Duzgunes N, Straubinger RM, Baldwin PA, Friend DS, Papahadjopoulos D. 1985. Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes. Biochemistry 24:3091–3098.
   PubMed Web of Science ®Google Scholar
• Edhemovic I, Snoj M, Kljun A, Golouh R. 2001. Immunohistochemical localization of group II phospholipase A2 in the tumours and mucosa of the colon and rectum. Eur J Surg Oncol 27:545–548.
   PubMedGoogle Scholar
• Elegbede AI, Banerjee J, Hanson AJ, Tobwala S, Ganguli B, Wang RY, Lu XN, Srivastava DK, Mallik S. 2008. Mechanistic studies of the triggered release of liposomal contents by matrix metalloproteinase-9. J Am Chem Soc 130:10633–10642.
   PubMed Web of Science ®Google Scholar
• Ellens H, Bentz J, Szoka FC. 1984. pH-induced destabilization of phosphatidylethanolamine-containing liposomes: role of bilayer contact. Biochemistry 23:1532–1538.
   PubMed Web of Science ®Google Scholar
• Emanuel N, Kedar E, Bolotin EM, Smorodinsky NI, Barenholz Y. 1996. Targeted delivery of doxorubicin via sterically stabilized immunoliposomes: pharmacokinetics and biodistribution in tumor-bearing mice. Pharm Res 13:861–868.
   PubMed Web of Science ®Google Scholar
• Gaber MH, Hong K, Huang SK, Papahadjopoulos D. 1995. Thermosensitive sterically stabilized liposomes: formulation and in vitro studies on mechanism of doxorubicin release by bovine serum and human plasma. Pharm Res 12:1407–1416.
   PubMed Web of Science ®Google Scholar
• Gaber MH, Wu NZ, Hong K, Huang SK, Dewhirst MW, Papahadjopoulos D. 1996. Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. Int J Radiat Oncol Biol Phys 36:1177–1187.
   PubMed Web of Science ®Google Scholar
• Gabizon A, Shmeeda H, Barenholz Y. 2003. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet 42:419–436.
   PubMed Web of Science ®Google Scholar
• Gabizon A, Shmeeda H, Horowitz AT, Zalipsky S. 2004. Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates. Adv Drug Deliv Rev 56:1177–1192.
   PubMed Web of Science ®Google Scholar
• Gabizon AA. 2001. Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin Cancer Res 7:223–225.
   PubMed Web of Science ®Google Scholar
• Gabizon AA, Tzemach D, Horowitz AT, Shmeeda H, Yeh J, Zalipsky S. 2006. Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based prodrug incorporated in pegylated liposomes. Clin Cancer Res 12:1913–1920.
   PubMed Web of Science ®Google Scholar
• Gerasimov OV, Boomer JA, Qualls MM, Thompson DH. 1999. Cytosolic drug delivery using pH- and light-sensitive liposomes. Adv Drug Del Rev 38:317–338.
   PubMed Web of Science ®Google Scholar
• Graff JR, Konicek BW, Deddens JA, Chedid M, Hurst BM, Colligan B, Neubauer BL, Carter HW, Carter JH. 2001. Expression of group IIa secretory phospholipase A2 increases with prostate tumor grade. Clin Cancer Res 7:3857–3861.
   PubMed Web of Science ®Google Scholar
• Haran G, Cohen R, Bar LK, Barenholz Y. 1993. Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta 1151:201–215.
   PubMed Web of Science ®Google Scholar
• Harrington KJ, Lewanski CR, Northcote AD, Whittaker J, Wellbank H, Vile RG, Peters AM, Stewart JS. 2001. Phase I-II study of pegylated liposomal cisplatin (SPI-077) in patients with inoperable head and neck cancer. Ann Oncol 12:493–496.
   PubMed Web of Science ®Google Scholar
• Hatakeyama H, Akita H, Kogure K, Harashima H. 2007a. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Yakugaku Zasshi 127:1549–1556.
   PubMedGoogle Scholar
• Hatakeyama H, Akita H, Kogure K, Oishi M, Nagasaki Y, Kihira Y, Ueno M, Kobayashi H, Kikuchi H, Harashima H. 2007b. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Ther 14:68–77.
   PubMed Web of Science ®Google Scholar
• Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H. 2009. A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J Control Release 139:127–132.
   PubMed Web of Science ®Google Scholar
• Hu LR, Ho RJY, Huang L. 1986. Trypsin induced destabilization of liposomes composed of dioleoylphosphatidylethanolamine and glyophorin. Biochem Biophys Res Comm 141:973–8.
   PubMed Web of Science ®Google Scholar
• Huang SL. 2008. Liposomes in ultrasonic drug and gene delivery. Adv Drug Deliv Rev 60:1167–1176.
   PubMed Web of Science ®Google Scholar
• Ishida T, Kirchmeier MJ, Moase EH, Zalipsky S, Allen TM. 2001. Targeted delivery and triggered release of liposomal doxorubicin enhances cytotoxicity against human B lymphoma cells. Biochim Biophys Acta 1515:144–158.
   PubMed Web of Science ®Google Scholar
• Jaracz S, Chen J, Kuznetsova LV, Ojima L. 2005. Recent advances in tumor-targeting anticancer drug conjugates. Bioorg Med Chem 13:5043–5054.
   PubMed Web of Science ®Google Scholar
• Jensen SS, Andresen TL, Davidsen J, Hoyrup P, Shnyder SD, Bibby MC, Gill JH, Jorgensen K. 2004. Secretory phospholipase A(2) as a tumor-specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer etherlipids. Mol Cancer Ther 3:1451–1458.
   PubMed Web of Science ®Google Scholar
• Jiang J, Neubauer BL, Graff JR, Chedid M, Thomas JE, Roehm NW, Zhang S, Eckert GJ, Koch MO, Eble JN, Cheng L. 2002. Expression of group IIA secretory phospholipase A2 is elevated in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Pathol 160:667–671.
   PubMed Web of Science ®Google Scholar
• Jølck RI, Berg RH, Andresen TL. 2010. Solid-phase synthesis of PEGylated lipopeptides using click chemistry. Bioconjugate Chem 21:807–810.
   PubMedGoogle Scholar
• Jorgensen K, Davidsen J, Mouritsen OG. 2002. Biophysical mechanisms of phospholipase A2 activation and their use in liposome-based drug delivery. FEBS Lett 531:23–27.
   PubMed Web of Science ®Google Scholar
• Jorgensen K, Vermehren C, Mouritsen OG. 1999. Enhancement of phospholipase A2 catalyzed degradation of polymer grafted PEG-liposomes: effects of lipopolymer-concentration and chain-length. Pharm Res 16:1491–1493.
   PubMed Web of Science ®Google Scholar
• Kaasgaard T, Andresen TL. 2010. Liposomal cancer therapy: exploiting tumor characteristics. Expert Opin Drug Deliv 7:225–243.
   PubMed Web of Science ®Google Scholar
• Kaasgaard T, Andresen TL, Jensen SS, Holte RO, Jensen LT, Jorgensen K. 2009. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery. Chem Phys Lipids 157:94–103.
   PubMed Web of Science ®Google Scholar
• Kashiwagi M, Friess H, Uhl W, Berberat P, Abou-Shady M, Martignoni M, Anghelacopoulos SE, Zimmermann A, Buchler MW. 1999. Group II and IV phospholipase (A2) are produced in human pancreatic cancer cells and influence prognosis. Gut 45:605–612.
   PubMed Web of Science ®Google Scholar
• Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong KL, Nielsen UB, Marks JD, Benz CC, Park JW. 2006. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res 66:6732–6740.
   PubMed Web of Science ®Google Scholar
• Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW. 2000. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 60:6950–6957.
   PubMed Web of Science ®Google Scholar
• Kudo I, Murakami M. 2002. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat 68–69:3–58.
   PubMed Web of Science ®Google Scholar
• Lamparski H, Liman U, Barry JA, Frankel DA, Ramaswami V, Brown MF, O'Brien DF. 1992. Photoinduced destabilization of liposomes. Biochemistry 31:685–694.
   PubMed Web of Science ®Google Scholar
• Laye JP, Gill JH. 2003. Phospholipase A2 expression in tumours: a target for therapeutic intervention? Drug Discov Today 8:710–716.
   PubMed Web of Science ®Google Scholar
• Leidy C, Linderoth L, Andresen TL, Mouritsen OG, Jorgensen K, Peters GH. 2006. Domain-induced activation of human phospholipase A(2) type IIA: local versus global lipid composition. Biophys J 90:3165–3175.
   PubMed Web of Science ®Google Scholar
• Lentacker I, Geers B, Demeester J, De Smedt SC, Sanders NN. 2010. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved. Mol Ther 18:101–108.
   PubMed Web of Science ®Google Scholar
• Leung SY, Chen X, Chu KM, Yuen ST, Mathy J, Ji J, Chan AS, Li R, Law S, Troyanskaya OG, Tu IP, Wong J, So S, Botstein D, Brown PO. 2002. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci USA 99:16203–16208.
   PubMed Web of Science ®Google Scholar
• Linderoth L, Peters GH, Madsen R, Andresen TL. 2009. Drug delivery by an enzyme-mediated cyclization of a lipid prodrug with unique bilayer-formation properties. Angew Chemie Int Ed 48:1823–1826.
   PubMed Web of Science ®Google Scholar
• Maeda H, Matsumura Y. 1989. Tumoritropic and lymphotropic principles of macromolecular drugs. Crit Rev Ther Drug Carrier Syst 6:193–210.
   PubMed Web of Science ®Google Scholar
• Menger FM, Johnston DE. 1991. Specific enzyme-induced decapsulation. J Am Chem Soc 113:5467–5468.
   Web of Science ®Google Scholar
• Miller CR, Bennett DE, Chang DY, O'Brien DF. 1996. Effect of liposomal composition on photoactivated liposome fusion. Biochemistry 35:11782–11790.
   PubMedGoogle Scholar
• Needham D, Anyarambhatla G, Kong G, Dewhirst MW. 2000. A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 60:1197–1201.
   PubMed Web of Science ®Google Scholar
• Needham D, Dewhirst MW. 2001. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev 53:285–305.
   PubMed Web of Science ®Google Scholar
• Nicol F, Nir S, Szoka FC. 1996. Effect of cholesterol and charge on pore formation in bilayer vesicles by a pH-sensitive peptide. Biophys J 71:3288–3301.
   PubMed Web of Science ®Google Scholar
• Pak CC, Ali S, Janoff AS, Meers P. 1998. Triggerable liposomal fusion by enzyme cleavage of a novel peptide-lipid conjugate. Biochim Biophys Acta 1372:13–27.
   PubMed Web of Science ®Google Scholar
• Pak CC, Erukulla RK, Ahl PL, Janoff AS, Meers P. 1999. Elastase activated liposomal delivery to nucleated cells. Biochim Biophys Acta 1419:111–126.
   PubMed Web of Science ®Google Scholar
• Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C. 1991. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 88:11460–11464.
   PubMed Web of Science ®Google Scholar
• Pedersen PJ, Christensen MS, Ruysschaert T, Linderoth L, Andresen TL, Melander F, Mouritsen OG, Madsen R, Clausen MH. 2009. Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs. J Med Chem 52:3408–3415.
   PubMed Web of Science ®Google Scholar
• Peters AC, Ahmad I, Janoff AS, Pushkareva MY, Mayhew E. 1997. Growth inhibitory effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine. Lipids 32:1045–1054.
   PubMedGoogle Scholar
• Pignatello R, Puleo A, Puglisi G, Vicari L, Messina A. 2003. Effect of liposomal delivery on in vitro antitumor activity of lipophilic conjugates of methotrexate with lipoamino acids. Drug Delivery 10:95–100.
   PubMed Web of Science ®Google Scholar
• Pinnaduwage P, Huang L. 1988. Beta-galactosidase-induced destabilization of liposome composed of phosphatidylethanolamine and ganglioside-GM1. Biochim Biophys Acta 939:375–382.
   PubMedGoogle Scholar
• Sarkar NR, Rosendahl T, Krueger AB, Banerjee AL, Benton K, Mallik S, Srivastava DK. 2005. ‘Uncorking’ of liposomes by matrix metalloproteinase-9. Chem Comm 8:999–1001.
   PubMedGoogle Scholar
• Schroeder A, Kost J, Barenholz Y. 2009. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes. Chem Phys Lipids 162:1–16.
   PubMed Web of Science ®Google Scholar
• Semple SC, Akinc A, Chen JX, Sandhu AP, Mui BL, Cho CK, Sah DWY, Stebbing D, Crosley EJ, Yaworski E, Hafez IM, Dorkin JR, Qin J, Lam K, Rajeev KG, Wong KF, Jeffs LB, Nechev L, Eisenhardt ML, Jayaraman M, Kazem M, Maier MA, Srinivasulu M, Weinstein MJ, Chen QM, Alvarez R, Barros SA, De S, Klimuk SK, Borland T, Kosovrasti V, Cantley WL, Tam YK, Manoharan M, Ciufolini MA, Tracy MA, de Fougerolles A, MacLachlan I, Cullis PR, Madden TD, Hope MJ. 2010. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176.
   PubMed Web of Science ®Google Scholar
• Seymour LW. 1992. Passive tumor targeting of soluble macromolecules and drug conjugates. Crit Rev Ther Drug Carrier Syst 9:135–187.
   PubMed Web of Science ®Google Scholar
• Shin J, Shum P, Thompson DH. 2003. Acid-triggered release via dePEGylation of DOPE liposomes containing acid-labile vinyl ether PEG-lipids. J Control Release 91:187–200.
   PubMed Web of Science ®Google Scholar
• Siddiqui RA, Jenski LJ, Neff K, Harvey K, Kovacs RJ, Stillwell W. 2001. Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process. Biochim Biophys Acta 1499:265–275.
   PubMed Web of Science ®Google Scholar
• Sofou S, Sgouros G. 2008. Anti body-targeted liposomes in cancer therapy and imaging. Expert Opin Drug Deliv 5:189–204.
   PubMed Web of Science ®Google Scholar
• Straus DS, Glass CK. 2001. Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med Res Rev 21:185–210.
   PubMed Web of Science ®Google Scholar
• Terada T, Iwai M, Kawakami S, Yamashita F, Hashida M. 2006. Novel PEG-matrix metalloproteinase-2 cleavable peptide-lipid containing galactosylated liposomes for hepatocellular carcinoma-selective targeting. J Control Release 111:333–342.
   PubMed Web of Science ®Google Scholar
• Turpeenniemi-Hujanen T. 2005. Gelatinases (MMP-2 and-9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie 87:287–297.
   PubMed Web of Science ®Google Scholar
• Uziely B, Jeffers S, Isacson R, Kutsch K, Wei-Tsao D, Yehoshua Z, Libson E, Muggia FM, Gabizon A. 1995. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol 13:1777–1785.
   PubMed Web of Science ®Google Scholar
• Venugopalan P, Jain S, Sankar S, Singh P, Rawat A, Vyas SP. 2002. pH-sensitive liposomes: mechanism of triggered release to drug and gene delivery prospects. Pharmazie 57:659–671.
   PubMed Web of Science ®Google Scholar
• Vihinen P, Ala-aho R, Kahari VM. 2005. Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targ 5:203–220.
   PubMed Web of Science ®Google Scholar
• Vihinen P, Kahari VM. 2002. Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166.
   PubMed Web of Science ®Google Scholar
• Visse R, Nagase H. 2003. Matrix metalloproteinases and tissue inhibitors of metalloproteinases – Structure, function, and biochemistry. Circulation Res 92:827–839.
   PubMed Web of Science ®Google Scholar
• Weinstein JN, Magin RL, Yatvin MB, Zaharko DS. 1979. Liposomes and local hyperthermia: selective delivery of methotrexate to heated tumors. Science 204:188–191.
   PubMed Web of Science ®Google Scholar
• Yamada A, Taniguchi Y, Kawano K, Honda T, Hattori Y, Maitani Y. 2008. Design of folate-linked liposomal doxorubicin to its antitumor effect in mice. Clin Cancer Res 14:8161–8168.
   PubMed Web of Science ®Google Scholar
• Yamashita S, Ogawa M, Sakamoto K, Abe T, Arakawa H, Yamashita J. 1994. Elevation of serum group II phospholipase A2 levels in patients with advanced cancer. Clin Chim Acta 228:91–99.
   PubMed Web of Science ®Google Scholar
• Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K, Ogawa M. 1993. Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells. Cancer 71:3058–3064.
   PubMed Web of Science ®Google Scholar
• Yatvin MB, Kreutz W, Horwitz BA, Shinitzky M. 1980. pH-sensitive liposomes: possible clinical implications. Science 210:1253–1255.
   PubMed Web of Science ®Google Scholar
• Yatvin MB, Weinstein JN, Dennis WH, Blumenthal R. 1978. Design of liposomes for enhanced local release of drugs by hyperthermia. Science 202:1290–1293.
   PubMed Web of Science ®Google Scholar
• Yavlovich A, Singh A, Tarasov S, Capala J, Blumenthal R, Puri A. 2009. Design of liposomes containing photopolymerizable phospholipids for triggered release of contents. J Therm Anal Calorim 98:97–104.
   PubMed Web of Science ®Google Scholar
• Yuan F, Leunig M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK. 1994. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res 54:3352–3356.
   PubMed Web of Science ®Google Scholar
• Zalipsky S, Saad M, Kiwan R, Ber E, Yu N, Minko T. 2007. Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor: Insights of the mechanism of action. J Drug Target 15:518–530.
   PubMed Web of Science ®Google Scholar
• Zerouga M, Stillwell W, Jenski LJ. 2002. Synthesis of a novel phosphatidylcholine conjugated to docosahexaenoic acid and methotrexate that inhibits cell proliferation. Anticancer Drugs 13:301–311.
   PubMed Web of Science ®Google Scholar