title: Tumor Microenvironment-Sensitive Liposomes Penetrate Tumor Tissue via Attenuated Interaction of the Extracellular Matrix and Tumor Cells and Accompanying Actin Depolymerization.
abstract: Delivery of anticancer drugs into tumor cores comprised of malignant cancer cells can result in potent therapeutic effects. However, conventional nanoparticle-based drug delivery systems used for cancer therapy often exhibit inefficient tumor-penetrating properties, thus, suggesting the need to improve the functional design of such systems. Herein, we focus on the interactions between cancer cells and the extracellular matrix (ECM) and demonstrate that liposomes modified with slightly acidic pH-sensitive peptide (SAPSp-lipo) can penetrate in vivo tumor tissue and in vitro spheroids comprised of cancer cells and ECM. We previously reported SAPSp-lipo, tumor microenvironment-sensitive liposomes, are effectively delivered to tumor tissue (Hama et al. J Control Release 2015, 206, 67-74). Compared with conventional liposomes, SAPSp-lipo could be delivered to deeper regions within both spheroids and tumor tissues. Furthermore, tumor penetration was found to be promoted at regions where actin depolymerization was induced by SAPSp-lipo and inhibited by the polymerization of actin. In addition, SAPSp-lipo attenuated the interaction between cancer cells and ECM, contributing to the penetration of SAPSp-lipo. These results suggest that SAPSp-lipo penetrates tumors via the interspace route and is accompanied by actin depolymerization. Taken together, SAPSp-lipo demonstrates potential as a novel tumor-penetrable drug carrier for induction of therapeutic effects against malignant cells that comprise tumor cores.
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Itakura
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsui
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nishi
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishimoto
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hama
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University , 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D058105:Polymerization; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments