title: Layer-by-layer nanoparticle platform for cancer active targeting.
abstract: Nanoparticles as drug delivery carriers have been investigated over the last few decades, particularly for cancer treatment. The rationale in developing such nanoparticles is to maximize drug efficacy while minimizing toxic side effects. This can be most effectively achieved through target specific drug delivery. A novel biocompatible nanoparticle platform prepared using the core-shell self-assembly technique is reported. The core consists of calcium phosphate which is biocompatible and pH-sensitive, and the shell is composed of biocompatible polymers (hyaluronic acid, CD44 targeting moiety; and chitosan, physical cross-linker). Cisplatin was selected as a model drug and incorporated between the core and the shell. The nanoparticle composition was optimized for high serum stability and low protein binding. These nanoparticles demonstrated target specific delivery in human lung cancer cells (which overexpress CD44 receptors). The targeting ability of the nanoparticles was confirmed with an 8-fold increase of drug efficacy (IC50) compared to cisplatin. Furthermore, the pH-sensitive core of the nanoparticle platform led to controlled drug release through destabilization in acidic conditions. This platform technology provides a simple approach for the design of targeted biocompatible nanoparticles for cancer therapy.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Suh
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Liisa T
authors.initials: LT
authors.lastname: Kuhn
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D048271:Chitosan; C020243:calcium phosphate; D002945:Cisplatin
keywords: CD44; Nanoparticles; Platform; Targeted cancer therapy; pH-sensitive