title: In vitro and in vivo imaging of peptide-encapsulated polymer nanoparticles for cancer biomarker activated drug delivery.
abstract: Gelatin nanoparticles coated with Cathepsin D-specific peptides were developed as a vehicle for the targeted delivery of the cancer drug doxorubicin (DOX) to treat breast malignancy. Cathepsin D, a breast cancer cell secretion enzyme, triggered the release of DOX by digesting the protective peptide-coating layer of nanoparticles. Fabricated nanoparticles were successfully detected with ultrasound imaging in both in vitro conditions and in vivo mouse cancer models. Cell viability experiments were conducted to determine the efficacy of biomarker activation specific to breast cancer cell lines. These experimental results were compared with the outcome of a viability experiment conducted on noncancerous cells. Viability decreased in human MCF7 mammary adenocarcinoma and mouse 4T1 mammary carcinoma cells, while that of noncancerous 3T3 fibroblast cells remained unaffected. Next, a real-time video of nanoparticle flow in mouse models was obtained using in vivo ultrasound imaging. The fluorescent profile of DOX was used as a means to examine nanoparticle localization in vivo. Results show the distribution of nanoparticles concentrated primarily within bladder and tumor sites of subject mice bodies. These findings support the use of biomarker coated nanoparticles in target specific therapy for breast cancer treatment.
authors: Gulsim K
authors: GK
authors: Kulsharova
authors: Matthew B
authors: MB
authors: Lee
authors: Felice
authors: F
authors: Cheng
authors: Munima
authors: M
authors: Haque
authors: Hyungsoo
authors: H
authors: Choi
authors: Kyekyoon
authors: K
authors: Kim
authors: William D
authors: WD
authors: O'Brien
authors: G Logan
authors: GL
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin
references: Macromol Biosci. 2008 Aug 11;8(8):758-65
references: 18446808
references: Adv Enzyme Regul. 2001;41:189-207
references: 11384745
references: Nucleic Acids Res. 1999 Jan 1;27(1):325-31
references: 9847218
references: Nat Rev Drug Discov. 2004 May;3(5):391-400
references: 15136787
references: J Control Release. 2003 Dec 5;93(2):151-60
references: 14636721
references: J Control Release. 2000 Mar 1;65(1-2):271-84
references: 10699287
references: Drug Discov Today. 2006 Sep;11(17-18):812-8
references: 16935749
references: J Pharm Pharmacol. 2013 Feb;65(2):157-70
references: 23278683
references: Macromol Biosci. 2007 Apr 10;7(4):423-8
references: 17429828
references: Oncol Nurs Forum. 2006 May 03;33(3):535-42
references: 16676010
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12617-21
references: 12235356
references: Biomaterials. 2009 Jul;30(21):3605-13
references: 19345993
references: Biomaterials. 1981 Oct;2(4):215-20
references: 7326315
references: Cancer Immunol Immunother. 2003 May;52(5):328-37
references: 12700948
references: Pharm Sci Technol Today. 2000 May;3(5):163-171
references: 10785658
references: J Control Release. 2005 Jan 20;102(1):113-22
references: 15653138