Coadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs

• Published in: Science (American Association for the Advancement of Science) Vol. 328; no. 5981; pp. 1031 - 1035
• Main Authors: Sugahara, Kazuki N., Teesalu, Tambet, Karmali, Priya Prakash, Kotamraju, Venkata Ramana, Agemy, Lilach, Greenwald, Daniel R., Ruoslahti, Erkki
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 21.05.2010; The American Association for the Advancement of Science
• Subjects: Albumin-Bound Paclitaxel; Albumins - administration & dosage; Albumins - pharmacokinetics; Albumins - therapeutic use; Animals; Antibodies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastics; Biological and medical sciences; Cancer; Capillary Permeability - drug effects; Chemotherapy; Constraining; Dosage; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Drugs; Humans; Intravenous injections; Liposomes; Medical sciences; Medical treatment; Mice; Molecules; Nanoparticles; Neoplasms - blood supply; Neoplasms - drug therapy; Neoplasms - metabolism; Neuropilin-1 - metabolism; Oligopeptides - administration & dosage; Oligopeptides - metabolism; Oligopeptides - pharmacokinetics; Oligopeptides - pharmacology; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Paclitaxel - therapeutic use; Peptides; Permeability; Pharmacology. Drug treatments; Prostate cancer; Side effects; Trastuzumab; Tumors; Xenograft Model Antitumor Assays; Antineoplastic agent; Performance evaluation; Drug; Animal model; Drug combination; Treatment efficiency; Rodentia; Malignant tumor; Route of administration; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Technique; Comparative study; Cancer
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1183057

Poor penetration of anticancer drugs into tumors can be an important factor limiting their effícacy. 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 effícacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.