title: Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression.
abstract: A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Sanjun
authors.initials: S
authors.lastname: Shi
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Shen
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: xunsun22@gmail.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D015195:Drug Design; D004357:Drug Synergism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D018960:Hyaluronan Receptors; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel
keywords: Co-delivery; MicroRNA; Paclitaxel; Synergistic cancer suppression; Tumor relapse