Hydrophobic Cysteine Poly(disulfide)-based Redox-Hypersensitive Nanoparticle Platform for Cancer Theranostics

Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus‐sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enha...

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Bibliographic Details
Published in:Angewandte Chemie (International ed.) 2015-08, Vol.54 (32), p.9218-9223
Main Authors: Wu, Jun, Zhao, Lili, Xu, Xiaoding, Bertrand, Nicolas, Choi, Won II, Yameen, Basit, Shi, Jinjun, Shah, Vishva, Mulvale, Matthew, MacLean, James L., Farokhzad, Omid C.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Antineoplastic Agents - toxicity
Cancer
Cell Line, Tumor
Cell Survival - drug effects
Cysteine
Cysteine - chemistry
disulfide
Disulfides - chemistry
Docetaxel
Drug Carriers - chemistry
Drug delivery systems
Fluorescence Resonance Energy Transfer
HeLa Cells
Humans
Hydrogen-Ion Concentration
hydrophobic
Hydrophobic and Hydrophilic Interactions
Hydrophobicity
Nanoparticles
Nanoparticles - chemistry
Nanostructure
Neoplasms - drug therapy
Oxidation-Reduction
Particle Size
Platforms
Polyethylene Glycols - chemistry
polymeric nanoparticle
Polymers - chemistry
redox response
Self assembly
Taxoids - administration & dosage
Taxoids - chemistry
Taxoids - toxicity
Theranostic Nanomedicine
Tumors
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Summary:Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus‐sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side‐effects. We report the development of a novel L‐cysteine‐based poly (disulfide amide) (Cys‐PDSA) family for fabricating redox‐triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt % docetaxel) and tunable properties. The polymers are synthesized through one‐step rapid polycondensation of two nontoxic building blocks: L‐cystine ester and versatile fatty diacids, which make the polymer redox responsive and give it a tunable polymer structure, respectively. Alterations to the diacid structure could rationally tune the physicochemical properties of the polymers and the corresponding NPs, leading to the control of NP size, hydrophobicity, degradation rate, redox response, and secondary self‐assembly after NP reductive dissociation. In vitro and in vivo results demonstrate these NPs’ excellent biocompatibility, high selectivity of redox‐triggered drug release, and significant anticancer performance. This system provides a promising strategy for advanced anticancer theranostic applications. Fatty diacid monomers were used to develop a hydrophobic cysteine poly(disulfide)‐based redox‐sensitive nanoparticle platform for cancer theranostics. With this model system, the relationships between polymer structure, nanoparticle hydrophobicity, and redox responsibility were demonstrated. In vitro and in vivo results showed excellent anticancer performance.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201503863