Pro-apoptotic peptides-based cancer therapies: challenges and strategies to enhance therapeutic efficacy

다국어 초록 (Multilingual Abstract)

Cancer is a leading cause of death worldwide.
Despite many advances in the field of cancer therapy, aneffective cure is yet to be found. As a more potent alternativefor the conventional small molecule anti-cancerdrugs, pro-apoptotic peptides have emerged as a new classof anticancer agents. By interaction with certain membersin the apoptotic pathways, they could effectively kill tumorcells. However, there remain bottleneck challenges forclinical application of these pro-apoptotic peptides incancer therapy. In this review, we will overview thedeveloped pro-apoptotic peptides and outline the widelyadopted molecular-based and nanoparticle-based strategiesto enhance their anti-tumor effects.

참고문헌 (Reference)

• 1 Mozhi A, "pH-sensitive polymeric micelles for the Co-delivery of proapoptotic peptide and anticancer drug for synergistic cancer therapy" 7 : 12886-12896, 2017
• 2 Levine AJ, "p53, the cellular gatekeeper for growth and division" 88 : 323-331, 1997
• 3 Hollstein M, "p53 mutations in human cancers" 253 : 49-53, 1991
• 4 Qifan W, "iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice" 37 : 10643-10652, 2016
• 5 Merkel O, "When the guardian sleeps: reactivation of the p53 pathway in cancer" 773 : 1-13, 2017
• 6 Yancopoulos GD, "Vascular-specific growth factors and blood vessel formation" 407 : 242-248, 2000
• 7 Sharma S, "Vascular changes in tumors resistant to a vascular disrupting nanoparticle treatment" 268 : 49-56, 2017
• 8 Prezma T, "VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for B-cell chronic lymphocytic leukemia" 4 : e809-, 2013
• 9 Holler N, "Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death-inducing signaling complex" 23 : 1428-1440, 2003
• 10 Akrami M, "Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms" 6 : 31030-, 2016
• 11 Sharma S, "Tumor-penetrating nanosystem strongly suppresses breast tumor growth" 17 : 1356-1364, 2017
• 12 Sugahara KN, "Tumor-penetrating iRGD peptide inhibits metastasis" 14 : 120-128, 2015
• 13 Corti A, "Tumor vasculature targeting through NGR peptide-based drug delivery systems" 12 : 1128-1134, 2011
• 14 Garanger E, "Tumor targeting with RGD peptide ligands-design of new molecular conjugates for imaging and therapy of cancers" 7 : 552-558, 2007
• 15 Ruoslahti E, "Tumor penetrating peptides for improved drug delivery" 110-111 : 3-12, 2017
• 16 Torchilin V, "Tumor delivery of macromolecular drugs based on the EPR effect" 63 : 131-135, 2011
• 17 Roth L, "Transtumoral targeting enabled by a novel neuropilin-binding peptide" 31 : 3754-3763, 2012
• 18 Schmaljohann D, "Thermo- and pH-responsive polymers in drug delivery" 58 : 1655-1670, 2006
• 19 Vigderman L, "Therapeutic platforms based on gold nanoparticles and their covalent conjugates with drug molecules" 65 : 663-676, 2013
• 20 Daniels TR, "The transferrin receptor and the targeted delivery of therapeutic agents against cancer" 1820 : 291-317, 2012
• 21 Harris MH, "The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability" 7 : 1182-1191, 2000
• 22 Yang ZJ, "The role of autophagy in cancer: therapeutic implications" 10 : 1533-1541, 2011
• 23 Seo YW, "The cell death-inducing activity of the peptide containing Noxa mitochondrial-targeting domain is associated with calcium release" 69 : 8356-8365, 2009
• 24 Fang J, "The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect" 63 : 136-151, 2011
• 25 Bouchet S, "The CNGRC-GG-D (KLAKLAK) 2 peptide induces a caspase-independent, Ca2 + -dependent death in human leukemic myeloid cells by targeting surface aminopeptidase N/CD13" 7 : 19445-, 2016
• 26 Adams JM, "The Bcl-2 protein family: arbiters of cell survival" 281 : 1322-1326, 1998
• 27 Youle RJ, "The BCL-2 protein family: opposing activities that mediate cell death" 9 : 47-59, 2008
• 28 Hong B, "Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities" 15 : 80-89, 2014
• 29 Hunt H, "Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles" 260 : 142-153, 2017
• 30 Ruoslahti E, "Targeting of drugs and nanoparticles to tumors" 188 : 759-768, 2010
• 31 Li K, "Targeting acute myeloid leukemia with a proapoptotic peptide conjugated to a Toll-like receptor 2-mediated cell-penetrating peptide" 134 : 692-702, 2014
• 32 Ahmad R, "Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer" 16 : 33-, 2017
• 33 Simon PO Jr, "Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma" 125 : 942-951, 2009
• 34 Dharap SS, "Targeted proapoptotic LHRH-BH3 peptide" 20 : 889-896, 2003
• 35 Leuschner C, "Targeted oncolytic peptide for treatment of ovarian cancers" 3 : 2017
• 36 Agemy L, "Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma" 108 : 17450-17455, 2011
• 37 Sudimack J, "Targeted drug delivery via the folate receptor" 41 : 147-162, 2000
• 38 Cieslewicz M, "Targeted delivery of proapoptotic peptides to tumor-associated macrophages improves survival" 110 : 15919-15924, 2013
• 39 Dufort S, "Targeted delivery of a proapoptotic peptide to tumors in vivo" 19 : 582-588, 2011
• 40 Curnis F, "Targeted delivery of IFNgamma to tumor vessels uncouples antitumor from counterregulatory mechanisms" 65 : 2906-2913, 2005
• 41 Shin MC, "Tandem-multimeric F3-gelonin fusion toxins for enhanced anti-cancer activity for prostate cancer treatment" 524 : 101-110, 2017
• 42 Belkahla H, "TRAIL-NP hybrids for cancer therapy: a review" 9 : 5755-5768, 2017
• 43 Chen G, "TNF-R1 signaling: a beautiful pathway" 296 : 1634-1635, 2002
• 44 Karageorgis A, "Systemic delivery of tumor-targeted bax-derived membrane-active peptides for the treatment of melanoma tumors in a humanized SCID mouse model" 25 : 534-546, 2017
• 45 Staquicini FI, "Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma" 121 : 161-173, 2011
• 46 Vlieghe P, "Synthetic therapeutic peptides: science and market" 15 : 40-56, 2010
• 47 Vrielink J, "Synthetic constrained peptide selectively binds and antagonizes death receptor 5" 277 : 1653-1665, 2010
• 48 Ngambenjawong C, "Synthesis and evaluation of multivalent M2pep peptides for targeting alternatively activated M2 macrophages" 224 : 103-111, 2016
• 49 An P, "Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library" 111 : 165-173, 2004
• 50 Yoshimori A, "Structure-based design of an agonistic peptide targeting Fas" 10 : 323-329, 2005
• 51 Colombo G, "Structure-activity relationships of linear and cyclic peptides containing the NGR tumor-homing motif" 277 : 47891-47897, 2002
• 52 Hoffman AS, "Stimuli-responsive polymers: biomedical applications and challenges for clinical translation" 65 : 10-16, 2013
• 53 Karimi M, "Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems" 45 : 1457-1501, 2016
• 54 Li M, "Smac therapeutic Peptide nanoparticles inducing apoptosis of cancer cells for combination chemotherapy with Doxorubicin" 7 : 8005-8012, 2015
• 55 Heldin CH, "Signal transduction via platelet-derived growth factor receptors" 1378 : F79-F113, 1998
• 56 Acar H, "Self-assembling peptide-based building blocks in medical applications" 110-111 : 65-79, 2017
• 57 Arlt A, "Role of NF-kappaB and Akt/PI3 K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death" 22 : 3243-3251, 2003
• 58 Herbst RS, "Review of epidermal growth factor receptor biology" 59 : 21-26, 2004
• 59 Eskandari S, "Recent advances in self-assembled peptides: Implications for targeted drug delivery and vaccine engineering" 110-111 : 169-187, 2017
• 60 조용연, "RSK2 and its binding partners in cell proliferation, transformation and cancer development" 대한약학회 40 (40): 291-303, 2017
• 61 Buckley CD, "RGD peptides induce apoptosis by direct caspase-3 activation" 397 : 534-539, 1999
• 62 Shin MC, "Preparation and characterization of gelonin-melittin fusion biotoxin for synergistically enhanced anti-tumor activity" 33 : 2218-2228, 2016
• 63 Yang L, "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide" 63 : 831-837, 2003
• 64 Prabhu RH, "Polymeric nanoparticles for targeted treatment in oncology: current insights" 10 : 1001-1018, 2015
• 65 Selbo PK, "Photochemical internalization provides time-and space-controlled endolysosomal escape of therapeutic molecules" 148 : 2-12, 2010
• 66 Norum OJ, "Photochemical internalization (PCI) in cancer therapy: from bench towards bedside medicine" 96 : 83-92, 2009
• 67 Martens CL, "Peptides which bind to E-selectin and block neutrophil adhesion" 270 : 21129-21136, 1995
• 68 Wu D, "Peptide-based cancer therapy: opportunity and challenge" 351 : 13-22, 2014
• 69 David A, "Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment" 119 : 120-142, 2017
• 70 Torchilin VP, "Peptide and protein drug delivery to and into tumors: challenges and solutions" 8 : 259-266, 2003
• 71 Torchilin VP, "Passive and active drug targeting: drug delivery to tumors as an example" 3-53, 2010
• 72 Rathore R, "Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)" 22 : 898-919, 2017
• 73 Tyuryaeva II, "Origin of anti-tumor activity of the cysteine-containing GO peptides and further optimization of their cytotoxic properties" 7 : 40217-, 2017
• 74 Christian S, "Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels" 163 : 871-878, 2003
• 75 Kumar M, "Novel polymeric nanoparticles for intracellular delivery of peptide Cargos: antitumor efficacy of the BCL-2 conversion peptide NuBCP-9" 74 : 3271-3281, 2014
• 76 Curtis KK, "Novel LHRH-receptor-targeted cytolytic peptide, EP-100: first-in-human phase I study in patients with advanced LHRH-receptor-expressing solid tumors" 73 : 931-941, 2014
• 77 Glinka Y, "Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity" 84 : 302-310, 2008
• 78 Kolodkin AL, "Neuropilin is a semaphorin III receptor" 90 : 753-762, 1997
• 79 Proskuryakov SY, "Necrosis: a specific form of programmed cell death?" 283 : 1-16, 2003
• 80 Ma L, "Nanoparticles for combination drug therapy" 7 : 9518-9525, 2013
• 81 Bobo D, "Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date" 33 : 2373-2387, 2016
• 82 Sarangthem V, "Multivalent targeting based delivery of therapeutic peptide using AP1-ELP carrier for effective cancer therapy" 6 : 2235-2249, 2016
• 83 Ngambenjawong C, "Multivalent polymers displaying M2 macrophage-targeting peptides improve target binding avidity and serum stability" 3 : 2050-2053, 2017
• 84 Chu DS, "Multivalent display of pendant pro-apoptotic peptides increases cytotoxic activity" 205 : 155-161, 2015
• 85 Pavet V, "Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity" 70 : 1101-1110, 2010
• 86 Curry T, "Multifunctional theranostic gold nanoparticles for targeted CT imaging and photothermal therapy" 9 : 53-61, 2014
• 87 Quinto CA, "Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment" 7 : 12728-12736, 2015
• 88 Luo GF, "Multifunctional enveloped mesoporous silica nanoparticles for subcellular co-delivery of drug and therapeutic peptide" 4 : 6064-, 2014
• 89 Zhang J, "Multifunctional envelope-type mesoporous silica nanoparticles for tumor-triggered targeting drug delivery" 135 : 5068-5073, 2013
• 90 Ham SH, "Molecular tumor targeting of gelonin by fusion with F3 peptide" 38 : 897-906, 2017
• 91 Shai Y, "Mode of action of membrane active antimicrobial peptides" 66 : 236-248, 2002
• 92 Farsinejad S, "Mitochondrial targeted peptides for cancer therapy" 36 : 5715-5725, 2015
• 93 Dai H, "Mitochondrial apoptosis and BH3 mimetics" 5 : 2804-, 2016
• 94 Tait SW, "Mitochondria and cell death: outer membrane permeabilization and beyond" 11 : 621-632, 2010
• 95 Green DR, "Mitochondria and apoptosis" 281 : 1309-1312, 1998
• 96 Slowing II, "Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins" 129 : 8845-8849, 2007
• 97 Slowing II, "Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers" 60 : 1278-1288, 2008
• 98 Han X, "Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin" 8 : 715-720, 2001
• 99 Wharton SA, "Membrane fusion by peptide analogues of influenza virus haemagglutinin" 69 : 1847-1857, 1988
• 100 Raghuraman H, "Melittin: a membrane-active peptide with diverse functions" 27 : 189-223, 2007
• 101 Wachter F, "Mechanistic validation of a clinical lead stapled peptide that reactivates p53 by dual HDM2 and HDMX targeting" 36 : 2184-2190, 2017
• 102 Tombacz E, "Magnetic iron oxide nanoparticles: Recent trends in design and synthesis of magnetoresponsive nanosystems" 468 : 442-453, 2015
• 103 Shamay Y, "Light induced drug delivery into cancer cells" 32 : 1377-1386, 2011
• 104 Allen TM, "Ligand-targeted therapeutics in anticancer therapy" 2 : 750-763, 2002
• 105 Zhong Y, "Ligand-directed active tumor-targeting polymeric nanoparticles for cancer chemotherapy" 15 : 1955-1969, 2014
• 106 Rezaei Araghi R, "Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells" 115 : E886-E895, 2018
• 107 Lee N, "Iron oxide based nanoparticles for multimodal imaging and magnetoresponsive therapy" 115 : 10637-10689, 2015
• 108 Duvall CL, "Intracellular delivery of a proapoptotic peptide via conjugation to a RAFT synthesized endosomolytic polymer" 7 : 468-476, 2010
• 109 Hasegawa M, "Intracellular Targeting of the Oncogenic MUC1-C Protein with a Novel GO-203 Nanoparticle Formulation" 21 : 2338-2347, 2015
• 110 Desgrosellier JS, "Integrins in cancer: biological implications and therapeutic opportunities" 10 : 9-22, 2010
• 111 Pollak M, "Insulin and insulin-like growth factor signalling in neoplasia" 8 : 915-928, 2008
• 112 Miao YR, "Inhibition of established micrometastases by targeted drug delivery via cell surface-associated GRP78" 19 : 2107-2116, 2013
• 113 Hossbach J, "Inhibiting the inhibitors: retro-inverso Smac peptides" 30 : 2374-2379, 2009
• 114 Standley SM, "Induction of cancer cell death by self-assembling nanostructures incorporating a cytotoxic peptide" 70 : 3020-3026, 2010
• 115 Zhong F, "Induction of Ca(2) + -driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction" 117 : 2924-2934, 2011
• 116 Erazo-Oliveras A, "Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges" 5 : 1177-1209, 2012
• 117 Binetruy-Tournaire R, "Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis" 19 : 1525-1533, 2000
• 118 Xin Q, "Identification of a novel peptide ligand of human transfrrin receptor 1 for targeted tumor delivery drug" 20 : 96-101, 2013
• 119 Schally AV, "Hypothalamic hormones and cancer" 22 : 248-291, 2001
• 120 Durrer P, "H + -induced membrane insertion of influenza virus hemagglutinin involves the HA2 amino-terminal fusion peptide but not the coiled coil region" 271 : 13417-13421, 1996
• 121 Li W, "GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery" 56 : 967-985, 2004
• 122 Alex S, "Functionalized gold nanoparticles: synthesis, properties and applications-a review" 15 : 1869-1894, 2015
• 123 Gaspar D, "From antimicrobial to anticancer peptides. A review" 4 : 294-, 2013
• 124 Nagata S, "Fas-mediated apoptosis" 406 : 119-124, 1996
• 125 Gu Y, "Evolving strategies for tumor immunotherapy: enhancing the enhancer and suppressing the suppressor" 4 : 161-163, 2017
• 126 Kern HB, "Enzyme-cleavable polymeric micelles for the intracellular delivery of proapoptotic peptides" 14 : 1450-1459, 2017
• 127 Lonn P, "Enhancing endosomal escape for intracellular delivery of macromolecular biologic therapeutics" 6 : 32301-, 2016
• 128 Dickerson EB, "Enhancement of the antiangiogenic activity of interleukin-12 by peptide targeted delivery of the cytokine to alphavbeta3 integrin" 2 : 663-673, 2004
• 129 Jiang Y, "Enhanced in vivo antitumor efficacy of dual-functional peptide-modified docetaxel nanoparticles through tumor targeting and Hsp90 inhibition" 221 : 26-36, 2016
• 130 Fu B, "Enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA on human brain metastatic breast cancer" 5 : 8029-, 2015
• 131 McDonald DM, "Endothelial cells of tumor vessels: abnormal but not absent" 19 : 109-120, 2000
• 132 Liu GW, "Efficient identification of murine M2 macrophage peptide targeting ligands by phage display and next-generation sequencing" 26 : 1811-1817, 2015
• 133 Nicholson RI, "EGFR and cancer prognosis" 37 (37): S9-S15, 2001
• 134 Chen WH, "Dual-targeting pro-apoptotic peptide for programmed cancer cell death via specific mitochondria damage" 3 : 3468-, 2013
• 135 Moschovi M, "Drugs acting on homeostasis: challenging cancer cell adaptation" 15 : 1405-1417, 2015
• 136 Sarosiek KA, "Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics-recent successes, current challenges and future promise" 283 : 3523-3533, 2016
• 137 Foight GW, "Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells" 9 : 1962-1968, 2014
• 138 Reinhardt A, "Design and application of antimicrobial peptide conjugates" 17 (17): 701-, 2016
• 139 Li H, "Delivery of intracellular-acting biologics in pro-apoptotic therapies" 17 : 293-319, 2011
• 140 Kamaly N, "Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release" 116 : 2602-2663, 2016
• 141 Alberici L, "De novo design of a tumor-penetrating peptide" 73 : 804-812, 2013
• 142 Javadpour MM, "De novo antimicrobial peptides with low mammalian cell toxicity" 39 : 3107-3113, 1996
• 143 Mulder KC, "Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides" 4 : 321-, 2013
• 144 Shah BP, "Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis" 8 : 9379-9387, 2014
• 145 Liu H, "Construction and expression of sTRAIL-melittin combining enhanced anticancer activity with antibacterial activity in Escherichia coli" 97 : 2877-2884, 2013
• 146 Kim AL, "Conformational and molecular basis for induction of apoptosis by a p53 C-terminal peptide in human cancer cells" 274 : 34924-34931, 1999
• 147 Kerbel R, "Clinical translation of angiogenesis inhibitors" 2 : 727-739, 2002
• 148 Huang K, "Cleavage by caspase 8 and mitochondrial membrane association activate the BH3-only protein Bid during TRAIL-induced apoptosis" 291 : 11843-11851, 2016
• 149 Baker SJ, "Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas" 244 : 217-221, 1989
• 150 Frankel AD, "Cellular uptake of the tat protein from human immunodeficiency virus" 55 : 1189-1193, 1988
• 151 Baluk P, "Cellular abnormalities of blood vessels as targets in cancer" 15 : 102-111, 2005
• 152 Shin MC, "Cell-penetrating peptides: achievements and challenges in application for cancer treatment" 102 : 575-587, 2014
• 153 Bechara C, "Cell-penetrating peptides: 20 years later, where do we stand?" 587 : 1693-1702, 2013
• 154 Wang H, "Cell-penetrating apoptotic peptide/p53 DNA nanocomplex as adjuvant therapy for drug-resistant breast cancer" 11 : 3352-3360, 2014
• 155 Verhagen AM, "Cell death regulation by the mammalian IAP antagonist Diablo/Smac" 7 : 163-166, 2002
• 156 Cole AJ, "Cancer theranostics: the rise of targeted magnetic nanoparticles" 29 : 323-332, 2011
• 157 Bertrand N, "Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology" 66 : 2-25, 2014
• 158 Xu X, "Cancer nanomedicine: from targeted delivery to combination therapy" 21 : 223-232, 2015
• 159 Holohan C, "Cancer drug resistance: an evolving paradigm" 13 : 714-726, 2013
• 160 Jung HK, "Bladder tumor-targeted delivery of pro-apoptotic peptide for cancer therapy" 235 : 259-267, 2016
• 161 Menard S, "Biologic and therapeutic role of HER2 in cancer" 22 : 6570-6578, 2003
• 162 Billard C, "BH3 mimetics: status of the field and new developments" 12 : 1691-1700, 2013
• 163 Mizushima N, "Autophagy: renovation of cells and tissues" 147 : 728-741, 2011
• 164 Yang L, "Aptamer-conjugated nanomaterials and their applications" 63 : 1361-1370, 2011
• 165 Plank C, "Application of membrane-active peptides for drug and gene delivery across cellular membranes" 34 : 21-35, 1998
• 166 Elmore S, "Apoptosis: a review of programmed cell death" 35 : 495-516, 2007
• 167 Haupt S, "Apoptosis-the p53 network" 116 : 4077-4085, 2003
• 168 Nagata S, "Apoptosis and clearance of apoptotic cells" 36 : 489-517, 2018
• 169 Thorburn A, "Apoptosis and autophagy: regulatory connections between two supposedly different processes" 13 : 1-9, 2008
• 170 Chari RV, "Antibody-drug conjugates: an emerging concept in cancer therapy" 53 : 3796-3827, 2014
• 171 Ellerby HM, "Anti-cancer activity of targeted proapoptotic peptides" 5 : 1032-1038, 1999
• 172 Portt L, "Anti-apoptosis and cell survival: a review" 1813 : 238-259, 2011
• 173 Pang HB, "An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability" 5 : 4904-, 2014
• 174 Ko JK, "Amphipathic tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides from Bcl-2 family proteins induce apoptosis through different mechanisms" 286 : 9038-9048, 2011
• 175 Pasqualini R, "Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis" 60 : 722-727, 2000
• 176 Laakkonen P, "A tumor-homing peptide with a targeting specificity related to lymphatic vessels" 8 : 751-755, 2002
• 177 Shi Y, "A structural view of mitochondria-mediated apoptosis" 8 : 394-401, 2001
• 178 Ma C, "A specific cell-penetrating peptide induces apoptosis in SKOV3 cells by down-regulation of Bcl-2" 35 : 1791-1797, 2013
• 179 Steichen SD, "A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics" 48 : 416-427, 2013
• 180 Kawamoto M, "A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells" 11 : 359-, 2011
• 181 Hetian L, "A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor" 277 : 43137-43142, 2002
• 182 Kohno M, "A novel hybrid peptide targeting EGFR-expressing cancers" 47 : 773-783, 2011
• 183 Chen WH, "A new anti-cancer strategy of damaging mitochondria by pro-apoptotic peptide functionalized gold nanoparticles" 49 : 6403-6405, 2013
• 184 Meyer M, "A dimethylmaleic acid-melittin-polylysine conjugate with reduced toxicity, pH-triggered endosomolytic activity and enhanced gene transfer potential" 9 : 797-805, 2007
• 185 Procko E, "A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells" 157 : 1644-1656, 2014