title: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs.
abstract: Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.
authors.affiliation: Vascular Mapping Laboratory, Center for Nanomedicine, Sanford-Burnham Medical Research Institute at University of California at Santa Barbara, Biology II Building, University of California, Santa Barbara, CA 93106-9610, USA.
authors.forename: Kazuki N
authors.initials: KN
authors.lastname: Sugahara
authors.forename: Tambet
authors.initials: T
authors.lastname: Teesalu
authors.forename: Priya Prakash
authors.initials: PP
authors.lastname: Karmali
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.forename: Lilach
authors.initials: L
authors.lastname: Agemy
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Greenwald
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010539:Permeability; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008081:Liposomes; D009842:Oligopeptides; D039942:Neuropilin-1; D004317:Doxorubicin; D000068878:Trastuzumab; D017239:Paclitaxel