Therapeutic Enzyme-Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors

An enzyme‐responsive, paclitaxel‐loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a proof‐of‐concept study demonstrating the utility of enzyme‐responsive nanoscale drug carriers capable of targeted accumulation and retention in tumo...

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Vydáno v:	Advanced materials (Weinheim) Ročník 27; číslo 31; s. 4611 - 4615
Hlavní autoři:	Callmann, Cassandra E., Barback, Christopher V., Thompson, Matthew P., Hall, David J., Mattrey, Robert F., Gianneschi, Nathan C.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Germany Blackwell Publishing Ltd 19.08.2015
Témata:	Animals Antineoplastic Agents, Phytogenic - administration & dosage Biomedical materials Cell Line, Tumor Cohort Studies Drug Carriers - chemistry drug delivery Drug Evaluation, Preclinical enzyme-responsive Fibrosarcoma - drug therapy Fibrosarcoma - enzymology Fluorescence Resonance Energy Transfer Human Humans In vivo testing In vivo tests Matrix Metalloproteinases - metabolism Maximum Tolerated Dose Mice, Nude Micelles Microscopy, Electron, Transmission nanomaterials Nanoparticles Nanoparticles - chemistry Neoplasm Transplantation Optical Imaging Paclitaxel - administration & dosage Polymers - chemistry self-assembly stimuli-responsive Surgical implants Tumor Burden Tumors Utilities self-assembly nanomaterials drug delivery enzyme-responsive stimuli-responsive
ISSN:	0935-9648, 1521-4095
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Abstract	An enzyme‐responsive, paclitaxel‐loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a proof‐of‐concept study demonstrating the utility of enzyme‐responsive nanoscale drug carriers capable of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enzymes.
AbstractList	An enzyme-responsive, paclitaxel-loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a proof-of-concept study demonstrating the utility of enzyme-responsive nanoscale drug carriers capable of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enzymes. In this Communication, we describe an enzyme-responsive, paclitaxel-loaded nanoparticle and assess its safety and efficacy in vivo in a human fibrosarcoma murine xenograft. The material was generated via graft-through block copolymerization of norbornene monomers with hydrophilic targeting peptides together with hydrophobic paclitaxel prodrugs. This work represents a proof-of-concept study demonstrating the utility of enzyme-responsive nanoscale drug carriers capable of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enzymes. Critically, we observed low systemic toxicity in healthy mice following intravenous administration, with the maximum tolerated dose (MTD) exceeding 240 mg/kg with respect to paclitaxel. Furthermore, we observed efficacy against tumorigenesis paralleling that of paclitaxel at equivalent intravenous dosing, and near complete tumor growth suppression when administered intratumorally. This work represents a significant departure from traditional targeted drug delivery systems and presents a new avenue of exploration for nanomedicine.
Author	Barback, Christopher V. Mattrey, Robert F. Callmann, Cassandra E. Hall, David J. Gianneschi, Nathan C. Thompson, Matthew P.
Author_xml	– sequence: 1 givenname: Cassandra E. surname: Callmann fullname: Callmann, Cassandra E. organization: Department of Chemistry and Biochemistry, University of California San Diego, CA, 92093, La Jolla, USA – sequence: 2 givenname: Christopher V. surname: Barback fullname: Barback, Christopher V. organization: Department of Radiology, University of California, San Diego, CA, 92093, La Jolla, USA – sequence: 3 givenname: Matthew P. surname: Thompson fullname: Thompson, Matthew P. organization: Department of Chemistry and Biochemistry, University of California San Diego, CA, 92093, La Jolla, USA – sequence: 4 givenname: David J. surname: Hall fullname: Hall, David J. organization: Department of Radiology, University of California, San Diego, CA, 92093, La Jolla, USA – sequence: 5 givenname: Robert F. surname: Mattrey fullname: Mattrey, Robert F. organization: Department of Radiology, University of California, San Diego, CA, 92093, La Jolla, USA – sequence: 6 givenname: Nathan C. surname: Gianneschi fullname: Gianneschi, Nathan C. email: ngianneschi@ucsd.edu organization: Department of Chemistry and Biochemistry, University of California San Diego, CA, 92093, La Jolla, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26178920$$D View this record in MEDLINE/PubMed
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Snippet	An enzyme‐responsive, paclitaxel‐loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a... An enzyme-responsive, paclitaxel-loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a... In this Communication, we describe an enzyme-responsive, paclitaxel-loaded nanoparticle and assess its safety and efficacy in vivo in a human fibrosarcoma...
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SubjectTerms	Animals Antineoplastic Agents, Phytogenic - administration & dosage Biomedical materials Cell Line, Tumor Cohort Studies Drug Carriers - chemistry drug delivery Drug Evaluation, Preclinical enzyme-responsive Fibrosarcoma - drug therapy Fibrosarcoma - enzymology Fluorescence Resonance Energy Transfer Human Humans In vivo testing In vivo tests Matrix Metalloproteinases - metabolism Maximum Tolerated Dose Mice, Nude Micelles Microscopy, Electron, Transmission nanomaterials Nanoparticles Nanoparticles - chemistry Neoplasm Transplantation Optical Imaging Paclitaxel - administration & dosage Polymers - chemistry self-assembly stimuli-responsive Surgical implants Tumor Burden Tumors Utilities
Title	Therapeutic Enzyme-Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors
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