pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents

References

• Aghi M, Martuza RL. 2005. Oncolytic viral therapies – the clinical experience. Oncogene, 24:7802–7816.
   PubMed Web of Science ®Google Scholar
• Andreev OA, Dupuy AD, Segala M, Sandugu S, Serra DA, Chichester CO, Engelman DM, Reshetnyak YK. 2007. Mechanism and uses of a membrane peptide that targets tumors and other acidic tissues in vivo. Proc Natl Acad Sci USA 104:7893–7898.
   PubMed Web of Science ®Google Scholar
• Andreev OA, Engelman DM, Reshetnyak YK. 2009. Targeting acidic diseased tissue. New technology based on use of the pH (Low) Insertion Peptide (pHLIP). Chemistry Today 27:10–13.
   Google Scholar
• Andreev OA, Karabadzhak AG, Weerakkody D, Andreev GO, Engelman DM, Reshetnyak YK. 2010. The pHLIP peptide inserts across a lipid bilayer as a helix, and exits by a different path Proc Natl Acad Sci USA.
   Google Scholar
• Andresen TL, Jensen SS, Jorgensen K. 2005. 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
• Balashov SP. 2000. Protonation reactions and their coupling in bacteriorhodopsin. Biochim Biophys Acta 1460:75–94.
   PubMedGoogle Scholar
• Becelli R, Renzi G, Morello R, Altieri F. 2007. Intracellular and extracellular tumor pH measurement in a series of patients with oral cancer. J Craniofac Surg 18:1051–1054.
   PubMed Web of Science ®Google Scholar
• Bhujwalla ZM, Artemov D, Ballesteros P, Cerdan S, Gillies RJ, Solaiyappan M. 2002. Combined vascular and extracellular pH imaging of solid tumors. NMR Biomed 15:114–119.
   PubMed Web of Science ®Google Scholar
• Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA Jr, Marks JR, Dressman HK, West M, Nevins JR. 2006. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439:353–357.
   PubMed Web of Science ®Google Scholar
• Bindra RS, Glazer PM. 2005. Genetic instability and the tumor microenvironment: Towards the concept of microenvironment-induced mutagenesis. Mutat Res 569:75–85.
   PubMed Web of Science ®Google Scholar
• Blättler WA, Chari RVJ. 2001. Drugs to enhance the therapeutic potency of anticancer antibodies, antibody-drug conjugates as tumor-activated prodrugs. Washington, DC: American Chemical Society.
   Google Scholar
• Brambillasca S, Yabal M, Makarow M, Borgese N. 2006. Unassisted translocation of large polypeptide domains across phospholipid bilayers. J Cell Biol 175:767–777.
   PubMedGoogle Scholar
• Brambillasca S, Yabal M, Soffientini P, Stefanovic S, Makarow M, Hegde RS, Borgese N. 2005. Transmembrane topogenesis of a tail-anchored protein is modulated by membrane lipid composition. EMBO J 24:2533–2542.
   PubMedGoogle Scholar
• Buchsbaum DJ. 2004. Imaging and therapy of tumors induced to express somatostatin receptor by gene transfer using radiolabeled peptides and single chain antibody constructs. Semin Nucl Med 34:32–46.
   PubMed Web of Science ®Google Scholar
• Carter P. 2001. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 1:118–129.
   PubMed Web of Science ®Google Scholar
• Davis ME, Chen ZG, Shin DM. 2008. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782.
   PubMed Web of Science ®Google Scholar
• de Bono JS, Tolcher AW, Forero A, Vanhove GF, Takimoto C, Bauer RJ, Hammond LA, Patnaik A, White ML, Shen S, Khazaeli MB, Rowinsky EK, LoBuglio AF. 2004. ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clin Cancer Res 10:7555–7465.
   PubMed Web of Science ®Google Scholar
• Duguet E, Vasseur S, Mornet S, Devoisselle JM. 2006. Magnetic nanoparticles and their applications in medicine. Nanomedicine 1:157–168.
   PubMed Web of Science ®Google Scholar
• Elayadi AN, Corey DR. 2001. Application of PNA and LNA oligomers to chemotherapy. Curr Opin Investig Drugs 2:558–561.
   PubMedGoogle Scholar
• Engelman DM, Chen Y, Chin CN, Curran AR, Dixon AM, Dupuy AD, Lee AS, Lehnert U, Matthews EE, Reshetnyak YK, Senes A, Popot JL. 2003. Membrane protein folding: Beyond the two stage model. FEBS Lett 555:122–125.
   PubMed Web of Science ®Google Scholar
• Everts B, van der Poel HG. 2005. Replication-selective oncolytic viruses in the treatment of cancer. Cancer Gene Ther 12:141–161.
   PubMed Web of Science ®Google Scholar
• Fais S. 2007. Cannibalism: A way to feed on metastatic tumors. Cancer Lett 258:155–164.
   PubMed Web of Science ®Google Scholar
• Freimark B, Clark D, Pernasetti F, Nickel J, Myszka D, Baeuerle PA, Van Epps D. 2007. Targeting of humanized antibody D93 to sites of angiogenesis and tumor growth by binding to multiple epitopes on denatured collagens. Mol Immunol 44:3741–3750.
   PubMedGoogle Scholar
• Ganta S, Devalapally H, Shahiwala A, Amiji M. 2008. A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release 126:187–204.
   PubMed Web of Science ®Google Scholar
• Gatenby RA, Gillies RJ. 2004. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899.
   PubMed Web of Science ®Google Scholar
• Gatenby RA, Gillies RJ. 2008. A microenvironmental model of carcinogenesis. Nat Rev Cancer 8:56–61.
   PubMed Web of Science ®Google Scholar
• Gatenby RA, Smallbone K, Maini PK, Rose F, Averill J, Nagle RB, Worrall L, Gillies RJ. 2007. Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer. Br J Cancer 97:646–653.
   PubMed Web of Science ®Google Scholar
• Ghosh N, Prat-Resina X, Gunner MR, Cui Q. 2009. Microscopic pKa analysis of Glu286 in cytochrome c oxidase (Rhodobacter sphaeroides): Toward a calibrated molecular model. Biochemistry 48:2468–2485.
   PubMedGoogle Scholar
• Gillies RJ, Liu Z, Bhujwalla Z. 1994. 31P-MRS measurements of extracellular pH of tumors using 3-aminopropylphosphonate. Am J Physiol 267:C195–203.
   PubMed Web of Science ®Google Scholar
• Gillies RJ, Robey I, Gatenby RA. 2008. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 49(Suppl. 2):24S–42S.
   PubMed Web of Science ®Google Scholar
• Gillies RJ, Schornack PA, Secomb TW, Raghunand N. 1999. Causes and effects of heterogeneous perfusion in tumors. Neoplasia 1:197–207.
   PubMedGoogle Scholar
• Gindy ME, Prud'homme RK. 2009. Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opin Drug Deliv 6:865–878.
   PubMed Web of Science ®Google Scholar
• Goldsmith SJ. 1997. Receptor imaging: Competitive or complementary to antibody imaging? Semin Nucl Med 27:85–93.
   PubMed Web of Science ®Google Scholar
• Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. 1996. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88–91.
   PubMed Web of Science ®Google Scholar
• Griffiths JR. 1991. Are cancer cells acidic? Br J Cancer 64:425–427.
   PubMed Web of Science ®Google Scholar
• Hainfeld JF, Slatkin DN, Smilowitz HM. 2004. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:309–315.
   PubMed Web of Science ®Google Scholar
• Hanke JH, Webster KR, Ronco LV. 2004. Protein biomarkers and drug design for cancer treatments. Eur J Cancer Prev 13:297–305.
   PubMedGoogle Scholar
• Holt A, Killian JA. 2009. Orientation and dynamics of transmembrane peptides: The power of simple models. Eur Biophys J 107:4081–4086.
   Google Scholar
• Holzer P. 2009. Acid-sensitive ion channels and receptors. Handb Exp Pharmacol 283–332.
   PubMedGoogle Scholar
• Hong SY, Oh JE, Lee KH. 1999. Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide. Biochem Pharmacol 58:1775–1780.
   PubMed Web of Science ®Google Scholar
• Hunt JF, Rath P, Rothschild KJ, Engelman DM. 1997. Spontaneous, pH-dependent membrane insertion of a transbilayer alpha-helix. Biochemistry 36:15177–15192.
   PubMed Web of Science ®Google Scholar
• Ito A, Shinkai M, Honda H, Kobayashi T. 2005. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 100:1–11.
   PubMed Web of Science ®Google Scholar
• Janssens JP, Verlinden I, Gungor N, Raus J, Michiels L. 2004. Protein biomarkers for breast cancer prevention. Eur J Cancer Prev 13:307–317.
   PubMedGoogle Scholar
• Jeffrey SS, Lonning PE, Hillner BE. 2005. Genomics-based prognosis and therapeutic prediction in breast cancer. J Natl Compr Canc Netw 3:291–300.
   PubMedGoogle Scholar
• Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J, Salli E, Kortesniemi M, Uusi-Simola J, Makitie A, Seppanen M, Minn H, Kotiluoto P, Auterinen I, Savolainen S, Kouri M, Joensuu H. 2007. Boron neutron capture therapy in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys 69:475–482.
   PubMed Web of Science ®Google Scholar
• Kellum JA, Song M, Li J. 2004. Science review. Extracellular acidosis and the immune response: Clinical and physiologic implications. Crit Care 8:331–336.
   PubMed Web of Science ®Google Scholar
• Kim KY. 2007. Nanotechnology platforms and physiological challenges for cancer therapeutics. Nanomedicine 3:103–110.
   PubMed Web of Science ®Google Scholar
• Knudsen H, Nielsen PE. 1997. Application of peptide nucleic acid in cancer therapy. Anticancer Drugs 8:113–118.
   PubMed Web of Science ®Google Scholar
• Krebs HA. 1972. The Pasteur effect and the relations between respiration and fermentation. Essays Biochem 8:1–34.
   PubMedGoogle Scholar
• Krenning EP, de Jong M, Kooij PP, Breeman WA, Bakker WH, de Herder WW, van Eijck CH, Kwekkeboom DJ, Jamar F, Pauwels S, Valkema R. 1999. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol 10(Suppl. 2):S23–29.
   PubMedGoogle Scholar
• Ladokhin AS, White SH. 2004. Interfacial folding and membrane insertion of a designed helical peptide. Biochemistry 43:5782–5791.
   PubMedGoogle Scholar
• Latorre M, Rinaldi C. 2009. Applications of magnetic nanoparticles in medicine: Magnetic fluid hyperthermia. P R Health Sci J 28:227–238.
   PubMed Web of Science ®Google Scholar
• LeBoeuf RA, Kerckaert GA, Aardema MJ, Gibson DP. 1990. Multistage neoplastic transformation of Syrian hamster embryo cells cultured at pH 6.70. Cancer Res 50:3722–3729.
   PubMedGoogle Scholar
• Liapi E, Geschwind JF. 2007. Transcatheter and ablative therapeutic approaches for solid malignancies. J Clin Oncol 25:978–986.
   PubMed Web of Science ®Google Scholar
• Lin E, Nemunaitis J. 2004. Oncolytic viral therapies. Cancer Gene Ther 11:643–664.
   PubMed Web of Science ®Google Scholar
• Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26.
   PubMed Web of Science ®Google Scholar
• Lister-James J, Moyer BR, Dean RT. 1997. Pharmacokinetic considerations in the development of peptide-based imaging agents. Q J Nucl Med 41:111–118.
   PubMedGoogle Scholar
• London E, Shahidullah K. 2009. Transmembrane vs. non-transmembrane hydrophobic helix topography in model and natural membranes. Curr Opin Struct Biol 19:464–472.
   PubMedGoogle Scholar
• Lora-Michiels M, Yu D, Sanders L, Poulson JM, Azuma C, Case B, Vujaskovic Z, Thrall DE, Charles HC, Dewhirst MW. 2006. Extracellular pH and P-31 magnetic resonance spectroscopic variables are related to outcome in canine soft tissue sarcomas treated with thermoradiotherapy. Clin Cancer Res 12:5733–5740.
   PubMed Web of Science ®Google Scholar
• Lu H, Goodell V, Disis ML. 2007. Targeting serum antibody for cancer diagnosis: A focus on colorectal cancer. Expert Opin Ther Targets 11:235–244.
   PubMed Web of Science ®Google Scholar
• Lugini L, Matarrese P, Tinari A, Lozupone F, Federici C, Iessi E, Gentile M, Luciani F, Parmiani G, Rivoltini L, Malorni W, Fais S. 2006. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res 66:3629–3638.
   PubMed Web of Science ®Google Scholar
• Ma L, Yu P, Veerendra B, Rold TL, Retzloff L, Prasanphanich A, Sieckman G, Hoffman TJ, Volkert WA, Smith CJ. 2007. In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7–14]NH2 peptide conjugate, a high-affinity fluorescent probe with high selectivity for the gastrin-releasing peptide receptor. Mol Imaging 6:171–180.
   PubMed Web of Science ®Google Scholar
• Martinez-Zaguilan R, Lynch RM, Martinez GM, Gillies RJ. 1993. Vacuolar-type H(+)-ATPases are functionally expressed in plasma membranes of human tumor cells. Am J Physiol 265:C1015–1029.
   PubMed Web of Science ®Google Scholar
• Martinez-Zaguilan R, Seftor EA, Seftor RE, Chu YW, Gillies RJ, Hendrix MJ. 1996. Acidic pH enhances the invasive behavior of human melanoma cells. Clin Exp Metastasis 14:176–186.
   PubMed Web of Science ®Google Scholar
• McIntyre JC, Sleight RG. 1991. Fluorescence assay for phospholipid membrane asymmetry. Biochemistry 30:11819–11827.
   PubMed Web of Science ®Google Scholar
• Mitin VN, Kulakov VN, Khokhlov VF, Sheino IN, Arnopolskaya AM, Kozlovskaya NG, Zaitsev KN, Portnov AA. 2009. Comparison of BNCT and GdNCT efficacy in treatment of canine cancer. Appl Radiat Isot 67:S299–301.
   PubMed Web of Science ®Google Scholar
• Moasser MM. 2007. Targeting the function of the HER2 oncogene in human cancer therapeutics. Oncogene 26:6577–6592.
   PubMed Web of Science ®Google Scholar
• Moghimi SM. 2006. Recent developments in polymeric nanoparticle engineering and their applications in experimental and clinical oncology. Anticancer Agents Med Chem 6:553–561.
   PubMed Web of Science ®Google Scholar
• Morita T, Nagaki T, Fukuda I, Okumura K. 1991. Effect of pH on the activity and stability of clastogens in the in vitro chromosomal aberration test with Chinese hamster ovary K1 cells. Mutat Res 262:159–166.
   PubMed Web of Science ®Google Scholar
• Morris KN, Weil MD, Malzbender R. 2006. Radiochromic film dosimetry of contrast-enhanced radiotherapy (CERT). Phys Med Biol 51:5915–5925.
   PubMedGoogle Scholar
• Munoz-Morris MA, Heitz F, Divita G, Morris MC. 2007. The peptide carrier Pep-1 forms biologically efficient nanoparticle complexes. Biochem Biophys Res Commun 355:877–882.
   PubMedGoogle Scholar
• Musial-Siwek M, Karabadzhak A, Andreev OA, Reshetnyak YK, Engelman DM. 2010. Tuning the insertion properties of pHLIP. Biochim Biophys Acta 1798:1041–1046.
   PubMedGoogle Scholar
• Muxi A, Pons F, Vidal-Sicart S, Setoain FJ, Herranz R, Novell F, Fernandez RM, Trias M, Setoain J. 1999. Radioimmunoguided surgery of colorectal carcinoma with an 111In-labelled anti-TAG72 monoclonal antibody. Nucl Med Commun 20:123–130.
   PubMed Web of Science ®Google Scholar
• Newell K, Franchi A, Pouyssegur J, Tannock I. 1993. Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc Natl Acad Sci USA 90:1127–1131.
   PubMed Web of Science ®Google Scholar
• Nielsen PE. 2005. Addressing the challenges of cellular delivery and bioavailability of peptide nucleic acids (PNA). Q Rev Biophys 38:345–350.
   PubMed Web of Science ®Google Scholar
• O'Connell MJ, Bachilo SM, Huffman CB, Moore VC, Strano MS, Haroz EH, Rialon KL, Boul PJ, Noon WH, Kittrell C, Ma J, Hauge RH, Weisman RB, Smalley RE. 2002. Band gap fluorescence from individual single-walled carbon nanotubes. Science 297:593–596.
   PubMed Web of Science ®Google Scholar
• O'Connor AE, Gallagher WM, Byrne AT. 2009. Porphyrin and nonporphyrin photosensitizers in oncology: Preclinical and clinical advances in photodynamic therapy. Photochem Photobiol 85:1053–1074.
   PubMed Web of Science ®Google Scholar
• Osborne AR, Rapoport TA, van den Berg B. 2005. Protein translocation by the Sec61/SecY channel. Annu Rev Cell Dev Biol 21:529–550.
   PubMed Web of Science ®Google Scholar
• Palumbo G. 2007. Photodynamic therapy and cancer: A brief sightseeing tour. Expert Opin Drug Deliv 4:131–148.
   PubMed Web of Science ®Google Scholar
• Park HJ, Lyons JC, Ohtsubo T, Song CW. 1999. Acidic environment causes apoptosis by increasing caspase activity. Br J Cancer 80:1892–1897.
   PubMed Web of Science ®Google Scholar
• Patel LN, Zaro JL, Shen WC. 2007. Cell penetrating peptides: Intracellular pathways and pharmaceutical perspectives. Pharm Res 24:1977–1992.
   PubMed Web of Science ®Google Scholar
• Payne G. 2003. Progress in immunoconjugate cancer therapeutics. Cancer Cell 3:207–212.
   PubMed Web of Science ®Google Scholar
• Pisarev MA, Dagrosa MA, Juvenal GJ. 2007. Boron neutron capture therapy in cancer: Past, present and future. Arq Bras Endocrinol Metabol 51:852–856.
   PubMedGoogle Scholar
• Polascik TJ, Manyak MJ, Haseman MK, Gurganus RT, Rogers B, Maguire RT, Partin AW. 1999. Comparison of clinical staging algorithms and 111indium-capromab pendetide immunoscintigraphy in the prediction of lymph node involvement in high risk prostate carcinoma patients. Cancer 85:1586–1592.
   PubMed Web of Science ®Google Scholar
• Raghunand N, Altbach MI, van Sluis R, Baggett B, Taylor CW, Bhujwalla ZM, Gillies RJ. 1999a. Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy. Biochem Pharmacol 57:309–312.
   PubMedGoogle Scholar
• Raghunand N, Gillies RJ. 2001. pH and chemotherapy. Novartis Found Symp 240:199–211; discussion 265–268.
   PubMedGoogle Scholar
• Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ. 1999b. Enhancement of chemotherapy by manipulation of tumour pH. Br J Cancer 80:1005–1011.
   PubMed Web of Science ®Google Scholar
• Raghunand N, Martinez-Zaguilan R, Wright SH, Gillies RJ. 1999c. pH and drug resistance. II. Turnover of acidic vesicles and resistance to weakly basic chemotherapeutic drugs. Biochem Pharmacol 57:1047–1058.
   PubMed Web of Science ®Google Scholar
• Reshetnyak YK, Andreev OA, Lehnert U, Engelman DM. 2006. Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. Proc Natl Acad Sci USA 103:6460–6465.
   PubMed Web of Science ®Google Scholar
• Reshetnyak YK, Andreev OA, Segala M, Markin VS, Engelman DM. 2008. Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane. Proc Natl Acad Sci USA 105:15340–15345.
   PubMed Web of Science ®Google Scholar
• Reshetnyak YK, Segala M, Andreev OA, Engelman DM. 2007. A monomeric membrane peptide that lives in three worlds: In solution, attached to, and inserted across lipid bilayers. Biophys J 93:2363–2372.
   PubMed Web of Science ®Google Scholar
• Robertson N, Potter C, Harris AL. 2004. Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion. Cancer Res 64:6160–6165.
   PubMed Web of Science ®Google Scholar
• Rofstad EK, Mathiesen B, Kindem K, Galappathi K. 2006. Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. Cancer Res 66:6699–6707.
   PubMed Web of Science ®Google Scholar
• Samad A, Alam MI, Saxena K. 2009. Dendrimers: A class of polymers in the nanotechnology for the delivery of active pharmaceuticals. Curr Pharm Des 15:2958–2969.
   PubMed Web of Science ®Google Scholar
• Schornack PA, Gillies RJ. 2003. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors. Neoplasia 5:135–145.
   PubMed Web of Science ®Google 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
• Semalty A, Semalty M, Rawat BS, Singh D, Rawat MS. 2009. Pharmacosomes: The lipid-based new drug delivery system. Expert Opin Drug Deliv 6:599–612.
   PubMed Web of Science ®Google Scholar
• Sennoune SR, Luo D, Martinez-Zaguilan R. 2004. Plasmalemmal vacuolar-type H+-ATPase in cancer biology. Cell Biochem Biophys 40:185–206.
   PubMed Web of Science ®Google Scholar
• Shai Y. 1999. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70.
   PubMed Web of Science ®Google Scholar
• Signore A, Annovazzi A, Chianelli M, Corsetti F, Van de Wiele C, Watherhouse RN. 2001. Peptide radiopharmaceuticals for diagnosis and therapy. Eur J Nucl Med 28:1555–1565.
   PubMedGoogle Scholar
• Srinivas PR, Kramer BS, Srivastava S. 2001. Trends in biomarker research for cancer detection. Lancet Oncol 2:698–704.
   PubMed Web of Science ®Google Scholar
• Sun H, Nikolovska-Coleska Z, Yang CY, Qian D, Lu J, Qiu S, Bai L, Peng Y, Cai Q, Wang S. 2008. Design of small-molecule peptidic and nonpeptidic Smac mimetics. Acc Chem Res 41:1264–1277.
   PubMed Web of Science ®Google Scholar
• Tannock IF, Rotin D. 1989. Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res 49:4373–4384.
   PubMed Web of Science ®Google Scholar
• Tekade RK, Kumar PV, Jain NK. 2009. Dendrimers in oncology: An expanding horizon. Chem Rev.
   PubMedGoogle Scholar
• Thevenin D, An M, Engelman DM. 2009. pHLIP-mediated translocation of membrane-impermeable molecules into cells. Chem Biol 16:754–762.
   PubMed Web of Science ®Google Scholar
• Thoren PE, Persson D, Karlsson M, Norden B. 2000. The antennapedia peptide penetratin translocates across lipid bilayers – the first direct observation. FEBS Lett 482:265–268.
   PubMed Web of Science ®Google Scholar
• Tsutsumi S, Neckers L. 2007. Extracellular heat shock protein 90: A role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci 98:1536–1539.
   PubMed Web of Science ®Google Scholar
• Van den Berg B, Clemons WM Jr, Collinson I, Modis Y, Hartmann E, Harrison SC, Rapoport TA. 2004. X-ray structure of a protein-conducting channel. Nature 427:36–44.
   PubMed Web of Science ®Google Scholar
• Vaupel P, Kallinowski F, Okunieff P. 1989. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res 49:6449–6465.
   PubMed Web of Science ®Google Scholar
• Vavere AL, Biddlecombe GB, Spees WM, Garbow JR, Wijesinghe D, Andreev OA, Engelman DM, Reshetnyak YK, Lewis JS. 2009. A novel technology for the imaging of acidic prostate tumors by positron emission tomography. Cancer Res 69:4510–4516.
   PubMedGoogle Scholar
• Vives E, Richard JP, Rispal C, Lebleu B. 2003. TAT peptide internalization: Seeking the mechanism of entry. Curr Protein Pept Sci 4:125–132.
   PubMed Web of Science ®Google Scholar
• Wang JL, Zhang ZJ, Choksi S, Shan S, Lu Z, Croce CM, Alnemri ES, Korngold R, Huang Z. 2000. Cell permeable Bcl-2 binding peptides: A chemical approach to apoptosis induction in tumor cells. Cancer Res 60:1498–1502.
   PubMed Web of Science ®Google Scholar
• Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J Gen Physiol 8:519–530.
   PubMedGoogle Scholar
• Wehland J, Osborn M, Weber K. 1977. Phalloidin-induced actin polymerization in the cytoplasm of cultured cells interferes with cell locomotion and growth. Proc Natl Acad Sci USA 74:5613–5617.
   PubMed Web of Science ®Google Scholar
• Wei LY, Roepe PD. 1994. Low external pH and osmotic shock increase the expression of human MDR protein. Biochemistry 33:7229–7238.
   PubMed Web of Science ®Google Scholar
• White SH, von Heijne G. 2004. The machinery of membrane protein assembly. Curr Opin Struct Biol 14:397–404.
   PubMedGoogle Scholar
• Williams AC, Collard TJ, Paraskeva C. 1999. An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: Implications for clonal selection during colorectal carcinogenesis. Oncogene 18:3199–3204.
   PubMed Web of Science ®Google Scholar
• Wimley WC, White SH. 2000. Determining the membrane topology of peptides by fluorescence quenching. Biochemistry 39:161–170.
   PubMedGoogle Scholar
• Xiong ZG, Pignataro G, Li M, Chang SY, Simon RP. 2008. Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol 8:25–32.
   PubMed Web of Science ®Google Scholar
• Yoo J, Cui Q. 2008. Does arginine remain protonated in the lipid membrane? Insights from microscopic pKa calculations. Biophys J 94:L61–63.
   Google Scholar
• Yuan J, Glazer PM. 1998. Mutagenesis induced by the tumor microenvironment. Mutat Res 400:439–446.
   PubMed Web of Science ®Google Scholar
• Zoonens M, Reshetnyak YK, Engelman DM. 2008. Bilayer interactions of pHLIP, a peptide that can deliver drugs and target tumors. Biophys J 95:225–235.
   PubMedGoogle Scholar