title: Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human lung cancer.
abstract: PLGA nanotherapeutics though representing a most promising platform for targeted cancer therapy are confronted with low stability and insufficient tumor cell uptake. Here, we report that hyaluronic acid (HA) coated PLGA nanoparticulate docetaxel (DTX-HPLGA) is particularly robust and can effectively target and suppress orthotopic human lung cancer. DTX-HPLGA was easily prepared with a small size of 154nm and negative surface charge of -22.7mV by nanoprecipitation and covalent coating with HA. DTX-HPLGA displayed a low IC50of 0.91μg/mL in CD44+ A549 cells and a prolonged elimination half-life of 4.13h in nude mice. Interestingly, DTX-HPLGA demonstrated 4.4-fold higher accumulation in the cancerous lung than free DTX, reaching a remarkable level of 13.7%ID/g at 8h post-injection, in orthotopic human A549 lung cancer-bearing mice. Accordingly, DTX-HPLGA exhibited significantly better inhibition of tumor growth than free DTX, leading to healthy mice growth and markedly improved survival time. DTX-HPLGA with easy fabrication, excellent stability and tumor accumulation, effective tumor suppression, and low side effects is of particular interest for targeted chemotherapy of lung cancers.
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Jintian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: cdeng@suda.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Meng
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Huanli
authors.initials: H
authors.lastname: Sun
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: zyzhong@suda.edu.cn.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid
keywords: Coating; Docetaxel; Lung cancer; Nanomedicine; PLGA nanoparticles