Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties

被引:10
作者
Bellat, Vanessa [1 ]
Lee, Hyun Hee [1 ]
Vahdat, Linda [2 ]
Law, Benedict [1 ]
机构
[1] Weill Cornell Med, Dept Radiol, Mol Imaging Innovat Inst, 413 East 69th St, New York, NY 10021 USA
[2] Weill Cornell Med, Dept Med, 425 East 61st St, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
SELF-ASSEMBLING PEPTIDE; CATHEPSIN-B; NANOFIBER; DEGRADATION; DELIVERY; STABILITY; ANTITUMOR; NANOPARTICLES; AMPHIPHILES; HYDROGEL;
D O I
10.1021/acs.biomac.6b00227
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously reported a high aspect ratio peptide nanofiber that could be effectively delivered to tumors with minimal nonspecific uptake by other organs. The peptidic nature offers the design flexibility of smart formulation with unique responsiveness. Two new formulations that behave congruously as nanotransformers (NTFs) are reported herein. NTF1 and NTF2 could biomechanically remodel upon enzyme activation to generate a degradable and an aggregable effect, respectively, within the lysosomal compartment. These NTFs were further evaluated as carriers of mertansine (DM1), a microtubule inhibitor. DM1-loaded NTF1 could be degraded by cathepsin B (CathB) to release the same active metabolite, as previously described in the lysosomal degradation of antibody-DM1 conjugate. In contrast, CathB only partially digested DM1-loaded NTF2 and induced aggregate become a storage reservoir with slow payload release property. The DM1-loaded NTF1 exhibited a comparable cytotoxicity to the free drug and was more effective than the NTF2 formulation in eradicating triple negative breast cancer. Our data- suggested that biological transformers with distinct enzyme-induced structural changes and payload release profiles could be designed for the intracellular delivery of cytotoxic and imaging agents.
引用
收藏
页码:2040 / 2049
页数:10
相关论文
共 51 条
[1]   Tunable Degradation of Maleimide-Thiol Adducts in Reducing Environments [J].
Baldwin, Aaron D. ;
Kiick, Kristi L. .
BIOCONJUGATE CHEMISTRY, 2011, 22 (10) :1946-1953
[2]   Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis [J].
Bian, Benjamin ;
Mongrain, Sebastien ;
Cagnol, Sebastien ;
Langlois, Marie-Josee ;
Boulanger, Jim ;
Bernatchez, Gerald ;
Carrier, Julie C. ;
Boudreau, Francois ;
Rivard, Nathalie .
MOLECULAR CARCINOGENESIS, 2016, 55 (05) :671-687
[3]   In vivo Near Infrared Fluorescence (NIRF) Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis [J].
Calfon, Marcella A. ;
Rosenthal, Amir ;
Mallas, Georgios ;
Mauskapf, Adam ;
Nudelman, R. Nika ;
Ntziachristos, Vasilis ;
Jaffer, Farouc A. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (54)
[4]   Therapeutic Enzyme-Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors [J].
Callmann, Cassandra E. ;
Barback, Christopher V. ;
Thompson, Matthew P. ;
Hall, David J. ;
Mattrey, Robert F. ;
Gianneschi, Nathan C. .
ADVANCED MATERIALS, 2015, 27 (31) :4611-4615
[5]   Improving Lanthanide Nanocrystal Colloidal Stability in Competitive Aqueous Buffer Solutions using Multivalent PEG-Phosphonate Ligands [J].
Cao, Pengpeng ;
Tong, Lemuel ;
Hou, Yi ;
Zhao, Guangyao ;
Guerin, Gerald ;
Winnik, Mitchell A. ;
Nitz, Mark .
LANGMUIR, 2012, 28 (35) :12861-12870
[6]   Recent developments in the maytansinoid antitumor agents [J].
Cassady, JM ;
Chan, KK ;
Floss, HG ;
Leistner, E .
CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (01) :1-26
[7]   Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release [J].
Chu, David S. H. ;
Johnson, Russell N. ;
Pun, Suzie H. .
JOURNAL OF CONTROLLED RELEASE, 2012, 157 (03) :445-454
[8]   Esterase-activated release of naproxen from supramolecular nanofibres [J].
Conda-Sheridan, Martin ;
Lee, Sungsoo S. ;
Preslar, Adam T. ;
Stupp, Samuel I. .
CHEMICAL COMMUNICATIONS, 2014, 50 (89) :13757-13760
[9]   Self-assembling amphiphilic peptides [J].
Dehsorkhi, Ashkan ;
Castelletto, Valeria ;
Hamley, Ian W. .
JOURNAL OF PEPTIDE SCIENCE, 2014, 20 (07) :453-467
[10]   Subcellular distribution of inorganic and methylated arsenic compounds in human urothelial cells and human hepatocytes [J].
Dopp, Elke ;
von Recklinghausen, Ursula ;
Hartmann, Louise M. ;
Stueckradt, Inga ;
Pollok, Ilona ;
Rabieh, Sasan ;
Hao, Liping ;
Nussler, Andreas ;
Katier, Cindy ;
Hirner, Alfred V. ;
Rettenmeier, Albert W. .
DRUG METABOLISM AND DISPOSITION, 2008, 36 (05) :971-979