title: Shell-crosslinked hybrid nanoparticles for direct cytosolic delivery for tumor therapy.
abstract: To obtain efficient therapeutics, drug release into the cytosol is required because drug targets are often located in the cytosol or have active sites that require intracellular machinery in the cytosolic compartment. However, typical nanocarriers gain cellular entry by endocytic mechanisms, confining the internalized nanocarriers to the endosomal-lysosomal system, thus resulting in the rapid destruction of active drugs without release into the cytosol. Herein, hybrid nanoparticles (HNs) with a core-shell structure, which was based on nanoemulsion-templates stabilized by both β-lactoglobulin (β-LG) and lecithin, were developed. Additionally, its formation mechanism and structure were also studied. Importantly, the HNs could directly penetrate the cell membrane and enter the cytosol, without entrapment within the endosomal-lysosomal system via the lipid raft-like pathway, thus enhancing its antitumor activities. We therefore concluded that HNs are promising targeting delivery systems for drugs, especially for pharmaceutical proteins and gene-targeting drugs.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lifangyin@hotmail.com.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D065546:Drug Liberation; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D007782:Lactoglobulins / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D007782:Lactoglobulins; D054709:Lecithins; D017239:Paclitaxel
keywords: Cellular uptake; Core–shell nanoparticles; Direct cytosolic delivery; Drug release; Inhibitors; Tumor therapy