title: pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block-short branched PEI for acidic cancer treatment.
abstract: To address cancer cell heterogeneity while endowing tumor specificity, the approach of charge shielding/deshielding was tested in vitro and in vivo with a paclitaxel loaded cationic micelle from a block copolymer of poly(L-histidine) (3.7kDa) and short branched polyethyleneimine (1.8 kDa). The cationic micelle surface was shielded by electrostatically complexing with a negatively charged mPEG (2 kDa)-block-polysulfadimethoxine (4 kDa) (mPEG-b-PSDM) at pH7.4. Unshielded micelle at pH7.4 and deshielded micelle at tumor extracellular pH were readily taken up by two wild types of human cancer cell lines, MCF-7 breast adenocarcinoma and SKOV-3 ovarian carcinoma, while the uptake of the shielded micelle at pH7.4 was minimal. The preliminary in vivo results from a mouse model xenografted with MCF-7 showed significant anticancer therapeutic efficacy and deep penetration of the micelle into tumor tissues after deshielding, supporting the unique pH-responsive mechanism to treat acidic cancer.
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Skaggs Research Building, Rm 2760, 30S, 2000E, Salt Lake City, 84112, USA.
authors: Jun
authors: J
authors: Hu
authors: Fuji Research Laboratories, Pharmaceutical Division, Kowa Co. Ltd., 332-1 Ohnoshinden, Fuji, Shizuoka, Japan.
authors: Seiji
authors: S
authors: Miura
authors: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Korea.
authors: Kun
authors: K
authors: Na
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Skaggs Research Building, Rm 2760, 30S, 2000E, Salt Lake City, 84112, USA; Utah-Inha Drug Delivery System and Advanced Therapeutics Research Center, Incheon, Korea. Electronic address: you.bae@utah.edu.
authors: You Han
authors: YH
authors: Bae
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; C033223:polyhistidine; D006639:Histidine; D011094:Polyethyleneimine; D017239:Paclitaxel
keywords: Extracellular pH; Micelle; Paclitaxel; Poly(l-histidine); Tumor heterogeneity; pH-sensitive block copolymer