title: Polymersome-mediated delivery of combination anticancer therapy to head and neck cancer cells: 2D and 3D in vitro evaluation.
abstract: Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumor cells, reducing off-target toxicity that often compromises anticancer treatment. Here, we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)- poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anticancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalized by HNSCC cells compared to normal oral cells. Polymersome cellular uptake was found to be mediated by class B scavenger receptors. We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumor models, PMPC-PDPA polymersomes were able to penetrate deep into the center of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC. Moreover, the preferential internalization of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumors.
authors.affiliation: School of Clinical Dentistry, University of Sheffield , Western Bank, Sheffield, South Yorkshire S10 2TN, U.K.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Colley
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hearnden
authors.forename: Milagros
authors.initials: M
authors.lastname: Avila-Olias
authors.forename: Denis
authors.initials: D
authors.lastname: Cecchin
authors.forename: Irene
authors.initials: I
authors.lastname: Canton
authors.forename: Jeppe
authors.initials: J
authors.lastname: Madsen
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.forename: Nicholas
authors.initials: N
authors.lastname: Warren
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes
authors.forename: Craig
authors.initials: C
authors.lastname: Murdoch
authors.forename: Martin H
authors.initials: MH
authors.lastname: Thornhill
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004134:Dimyristoylphosphatidylcholine / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017239:Paclitaxel / Q000008:administration & dosage; D011109:Polymethacrylic Acids / Q000008:administration & dosage*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); D004317:Doxorubicin; D017239:Paclitaxel; D004134:Dimyristoylphosphatidylcholine