title: Effect of octreotide surface density on receptor-mediated endocytosis in vitro and anticancer efficacy of modified nanocarrier in vivo after optimization.
abstract: The objective of the present work was to investigate the optimum density of octreotide on the surface of nanostructured lipid carriers (NLC) loaded with hydroxycamptothencine (HCPT) to enhance receptor-mediated endocytosis and tumor targeting selectivity. Different amounts of octreotide-polyethylene glycol (100) monostearate (OPMS), a ligand for somatostatin receptors (SSTRs), were coupled into NLC. In vitro evaluation of OPMS modified NLCs (O-NLCs) was done by studying the physicochemical properties, drug release, cellular uptake and cytotoxicity. Whereas in vivo evaluation was done by studying the tissue distribution in S180 tumor-bearing mice through ex vivo fluorescence imaging and HCPT quantitative study. The results showed that O-NLCs with an average size of ∼100 nm possessed obvious sustained release. When OPMS was used in the amount of 5 μmol (O₅-NLC) highest cellular uptake, cytotoxicity in SMMC-7721 cell line and remarkable accumulation in S180 tumor were observed. The treatments of O₅-NLC brought about significant tumor inhibition and prolonged the median survival time as compared with HCPT, unmodified NLC and the pegylated NLC (P₅-NLC) groups. It appears that to achieve a more rational approach of receptor mediated tumor targeted drug delivery system the surface density of the targeting moiety on the surface of nanocarriers should be considered.
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Zhigui
authors: Z
authors: Su
authors: Yongping
authors: Y
authors: Shi
authors: Yanyu
authors: Y
authors: Xiao
authors: Minjie
authors: M
authors: Sun
authors: Qineng
authors: Q
authors: Ping
authors: Li
authors: L
authors: Zong
authors: Sai
authors: S
authors: Li
authors: Jiangxiu
authors: J
authors: Niu
authors: Aiwen
authors: A
authors: Huang
authors: Weiliang
authors: W
authors: You
authors: Yinan
authors: Y
authors: Chen
authors: Xi
authors: X
authors: Chen
authors: Jia
authors: J
authors: Fei
authors: Jia
authors: J
authors: Tian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004705:Endocytosis; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000378:metabolism; D013499:Surface Properties; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D017481:Receptors, Somatostatin; D011092:Polyethylene Glycols; C009314:polyethylene glycol monostearate; D015282:Octreotide; D002166:Camptothecin