Delivery of doxorubicin in vitro and in vivo using bio-reductive cellulose nanogels.

A methacrylation strategy was used to functionalize carboxymethyl cellulose and prepare redox-sensitive cellulose nanogels which contained disulfide bonds. Dynamic light scattering, zeta potential and electron microscopy were utilized to characterize these nanogels. It was found that these nanogels had a spherical morphology with a diameter of about 192 nm, and negative surface potential. These redox-sensitive nanogels were stable against high salt concentration but de-integrated in the reducing environment containing glutathione. When doxorubicin (DOX) was loaded into the nanogels, a high drug loading content (36%) and a high encapsulation efficiency (83%) were achieved. Confocal laser scanning microscopy and co-localization images showed that DOX-loaded nanogels were internalized by the cancer cells through endocytosis and the DOX could be delivered into the nucleus. Near-infrared fluorescence imaging biodistribution examination indicated that the nanogels could passively target to the tumor area by the EPR effect and had a significantly prolonged circulation time. In vivo antitumor evaluation found that DOX-loaded nanogels exhibited a significantly superior antitumor effect than the free DOX by combining the tumor volume measurement and the examination of cell apoptosis and proliferation in tumor tissues.

[1]  Zhishen Ge,et al.  Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. , 2013, Chemical Society reviews.

[2]  K. Akiyoshi,et al.  Cationic amphiphilic polysaccharide nanoballs: protein stabilization and intracellular delivery by nano-encapsulation. , 2013, Biomaterials science.

[3]  K. Matyjaszewski,et al.  Smart heparin-based bioconjugates synthesized by a combination of ATRP and click chemistry , 2013 .

[4]  Arun K Iyer,et al.  Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors. , 2013, Biomaterials.

[5]  A. Müller,et al.  Interpolyelectrolyte complexes based on hyaluronic acid-block-poly(ethylene glycol) and poly-L-lysine , 2013 .

[6]  R. Sun,et al.  Preparation of cellulose-graft-poly(ɛ-caprolactone) nanomicelles by homogeneous ROP in ionic liquid. , 2013, Carbohydrate polymers.

[7]  Sayaka Hirano,et al.  Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle. , 2013, Biomacromolecules.

[8]  Jiaming Zhuang,et al.  Polymer nanogels: a versatile nanoscopic drug delivery platform. , 2012, Advanced drug delivery reviews.

[9]  Zhi Yuan,et al.  Doxorubicin-loaded glycyrrhetinic acid-modified alginate nanoparticles for liver tumor chemotherapy. , 2012, Biomaterials.

[10]  Y. Chau,et al.  One-step "click" method for generating vinyl sulfone groups on hydroxyl-containing water-soluble polymers. , 2012, Biomacromolecules.

[11]  S. Nie,et al.  Targeted delivery of cisplatin to lung cancer using ScFvEGFR-heparin-cisplatin nanoparticles. , 2011, ACS nano.

[12]  Shyh-Dar Li,et al.  Synthetic modification of carboxymethylcellulose and use thereof to prepare a nanoparticle forming conjugate of docetaxel for enhanced cytotoxicity against cancer cells. , 2011, Bioconjugate chemistry.

[13]  Robin S. Dothager,et al.  Nano in cancer: linking chemistry, biology, and clinical applications in vivo. , 2011, Cancer research.

[14]  S. Eichhorn,et al.  Cross-linked bacterial cellulose networks using glyoxalization. , 2011, ACS applied materials & interfaces.

[15]  N. Nishiyama,et al.  Polyion complex stability and gene silencing efficiency with a siRNA-grafted polymer delivery system. , 2010, Biomaterials.

[16]  F. Wen,et al.  Preparation of three-dimensional interconnected macroporous cellulosic hydrogels for soft tissue engineering. , 2010, Biomaterials.

[17]  M. Matsusaki,et al.  Preparation of Reduction-sensitive Nanogels with a Large Swelling Capacity by a Surfactant-free Precipitation Method , 2010 .

[18]  Robert Langer,et al.  Poly(ethylene glycol) with observable shedding. , 2010, Angewandte Chemie.

[19]  Yujiang Fan,et al.  Disassemblable micelles based on reduction-degradable amphiphilic graft copolymers for intracellular delivery of doxorubicin. , 2010, Biomaterials.

[20]  J. Rieger,et al.  Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization , 2010 .

[21]  Joseph M. DeSimone,et al.  Strategies in the design of nanoparticles for therapeutic applications , 2010, Nature Reviews Drug Discovery.

[22]  Ru Cheng,et al.  Shell-sheddable micelles based on dextran-SS-poly(epsilon-caprolactone) diblock copolymer for efficient intracellular release of doxorubicin. , 2010, Biomacromolecules.

[23]  S. Fort,et al.  Thermoresponsive vesicular morphologies obtained by self-assemblies of hybrid oligosaccharide-block-poly(N-isopropylacrylamide) copolymer systems. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[24]  S. Nicoll,et al.  Characterization of novel photocrosslinked carboxymethylcellulose hydrogels for encapsulation of nucleus pulposus cells. , 2010, Acta biomaterialia.

[25]  Ru Cheng,et al.  Reversibly stabilized multifunctional dextran nanoparticles efficiently deliver doxorubicin into the nuclei of cancer cells. , 2009, Angewandte Chemie.

[26]  Ick Chan Kwon,et al.  Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: synthesis, characterization, and in vivo biodistribution. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[27]  A. Kabanov,et al.  Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. , 2009, Angewandte Chemie.

[28]  Alessandro Sannino,et al.  Biodegradable Cellulose-based Hydrogels: Design and Applications , 2009, Materials.

[29]  Sylvia Notenboom,et al.  Glutathione dysregulation and the etiology and progression of human diseases , 2009, Biological chemistry.

[30]  Y. Bae,et al.  Stability issues of polymeric micelles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[31]  D. Ding,et al.  Synthesis of hydroxypropylcellulose-poly(acrylic acid) particles with semi-interpenetrating polymer network structure. , 2008, Biomacromolecules.

[32]  Zhuang Liu,et al.  Drug delivery with carbon nanotubes for in vivo cancer treatment. , 2008, Cancer research.

[33]  T. Park,et al.  Synthesis, characterization, and intracellular delivery of reducible heparin nanogels for apoptotic cell death. , 2008, Biomaterials.

[34]  K. Ulbrich,et al.  New HPMA copolymer-based drug carriers with covalently bound hydrophobic substituents for solid tumour targeting. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[35]  C. Highley,et al.  The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives. , 2007, Biomaterials.

[36]  Craig J Hawker,et al.  Cross-linked block copolymer micelles: functional nanostructures of great potential and versatility. , 2006, Chemical Society reviews.

[37]  V. Torchilin.  Fluorescence microscopy to follow the targeting of liposomes and micelles to cells and their intracellular fate. , 2005, Advanced drug delivery reviews.

[38]  Robert Langer,et al.  Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. , 2005, Biomacromolecules.

[39]  L. Nicolais,et al.  Cellulose derivative-hyaluronic acid-based microporous hydrogels cross-linked through divinyl sulfone (DVS) to modulate equilibrium sorption capacity and network stability. , 2004, Biomacromolecules.

[40]  Takehisa Matsuda,et al.  Trans-tissue, sustained release of gemcitabine from photocured gelatin gel inhibits the growth of heterotopic human pancreatic tumor in nude mice. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  Haixiong Ge,et al.  Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles. , 2002, Biomaterials.

[42]  James B. Mitchell,et al.  Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels. , 2002, Cancer research.

[43]  Freya Q. Schafer,et al.  Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. , 2001, Free radical biology & medicine.