title: Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation.
abstract: BACKGROUND
  Development of anticancer drugs is challenging. Indeed, much research effort has been spent in the development of new drugs to improve clinical outcomes with minimal toxicity. We have previously reported that a formulation of lipid gold porphyrin nanoparticles reduced systemic drug toxicity when compared with free gold porphyrin. In this study, we investigated the delivery and treatment efficiency of PEG surface-modified lipid nanoparticles as a carrier platform.
  
  
  METHODS
  We encapsulated antitumor drugs into PEG-modified lipid nanoparticles and these were characterized by size, zeta potential, and encapsulation efficiency. The delivery efficiency into tumor tissue was evaluated using a biodistribution study. To evaluate antitumor efficacy, gold porphyrin or camptothecin (a DNA topoisomerase I inhibitor) were encapsulated and compared using an in vivo neuroblastoma (N2A) model.
  
  
  RESULTS
  We showed that drug encapsulation into PEG-modified lipid nanoparticles enhanced the preferential uptake in tumor tissue. Furthermore, higher tumor killing efficiency was observed in response to treatment with PEG-modified lipid nanoparticles encapsulating gold porphyrin or camptothecin when compared with free gold porphyrin or free camptothecin. The in vivo antitumor effect was further confirmed by study of tumor inhibition and positive apoptosis activity. Surface modification of lipophilic nanoparticles with PEG increased the efficiency of drug delivery into tumor tissue and subsequently more effective antitumor activity.
  
  
  CONCLUSIONS
  This specific design of a chemotherapeutic agent using nanotechnology is important in the development of a safe and effective drug in cancer therapy.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.
authors.forename: Puiyan
authors.initials: P
authors.lastname: Lee
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Zhang
authors.forename: Vincent
authors.initials: V
authors.lastname: Li
authors.forename: Xuelai
authors.initials: X
authors.lastname: Liu
authors.forename: Raymond W Y
authors.initials: RW
authors.lastname: Sun
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
authors.forename: Kenneth K Y
authors.initials: KK
authors.lastname: Wong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006046:Gold / Q000737:chemistry; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D053769:Nanocapsules; D011166:Porphyrins; D011092:Polyethylene Glycols; D006046:Gold; D002166:Camptothecin