Nano-Sized Albumin-Copolymer Micelles for Efficient Doxorubicin Delivery

We present the discovery of a nano-sized protein-derived micellar drug delivery system based on the polycationic albumin precursor protein cBSA-147. The anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized micelles based on hydrophobic interactions with the polypeptide scaffold. These micelles revealed attractive stabilities in various physiological buffers and a wide pH range as well as very efficient uptake into A549 cells after 1 h incubation time only. In vitro cytotoxicity was five-times increased compared to free DOX also indicating efficient intracellular drug release. In addition, multiple functional groups are available for further chemical modifications. Based on the hydrophobic loading mechanism, various classical anti-cancer drugs, in principle, could be delivered even synergistically in a single micelle. Considering these aspects, this denatured albumin-based drug delivery system represents a highly attractive platform for nanomedicine approaches towards cancer therapy.

[1]  H. Luhmann,et al.  Fine-tuning DNA/albumin polyelectrolyte interactions to produce the efficient transfection agent cBSA-147. , 2010, Biomaterials.

[2]  D. Butterfield,et al.  Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. , 2010, Advances in experimental medicine and biology.

[3]  J. Dobson,et al.  Nanomedicine for targeted drug delivery , 2009 .

[4]  T. Weil,et al.  Preparation of Defined Albumin-Polymer Hybrids for Efficient Cell Transfection , 2010 .

[5]  Demin Liu,et al.  Nanoscale metal-organic frameworks for biomedical imaging and drug delivery. , 2011, Accounts of chemical research.

[6]  Aibing Yu,et al.  Inorganic nanoparticles as carriers for efficient cellular delivery , 2006 .

[7]  N. K. Jain,et al.  Application of dendrimer–drug complexation in the enhancement of drug solubility and bioavailability , 2008, Expert opinion on drug metabolism & toxicology.

[8]  J. Fréchet,et al.  Dendrimers and dendritic polymers in drug delivery. , 2005, Drug discovery today.

[9]  Dongmei Ren,et al.  Protein nanocapsules containing doxorubicin as a pH-responsive delivery system. , 2011, Small.

[10]  Eva Frei,et al.  Native albumin for targeted drug delivery , 2010, Expert opinion on drug delivery.

[11]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[12]  Sek-Man Wong,et al.  Folic acid-conjugated protein cages of a plant virus: a novel delivery platform for doxorubicin. , 2007, Bioconjugate chemistry.

[13]  J. G. Michael Cationization of protein antigens. VI. Effects of cationization on the immunoregulatory properties of a bovine serum albumin peptide, a.a. 506-589. , 1991, Cellular immunology.

[14]  T. Okano,et al.  Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[15]  H. Spiess,et al.  The distribution of fatty acids reveals the functional structure of human serum albumin. , 2010, Angewandte Chemie.

[16]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Jinming Gao,et al.  Polymeric nanomedicine for cancer MR imaging and drug delivery. , 2009, Chemical communications.

[18]  T. Weil,et al.  pH-Responsive quantum dots via an albumin polymer surface coating. , 2010, Journal of the American Chemical Society.

[19]  T. Peters,et al.  All About Albumin: Biochemistry, Genetics, and Medical Applications , 1995 .

[20]  T. Park,et al.  Doxorubicin-conjugated biodegradable polymeric micelles having acid-cleavable linkages. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[21]  H. Iwase,et al.  Nab-paclitaxel for the treatment of breast cancer: efficacy, safety, and approval , 2011, OncoTargets and therapy.

[22]  T Lammers,et al.  Tumour-targeted nanomedicines: principles and practice , 2008, British Journal of Cancer.

[23]  T. Terme,et al.  Albumin-Bound Paclitaxel: The Benefit of This New Formulation in the Treatment of Various Cancers , 2011, Journal of chemotherapy.

[24]  B. Říhová Clinical experience with anthracycline antibiotics-HPMA copolymer-human immunoglobulin conjugates. , 2009, Advanced drug delivery reviews.

[25]  Kostas Kostarelos,et al.  Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. , 2011, Accounts of chemical research.

[26]  T. Weil,et al.  Tailored Albumin-based Copolymers for Receptor-Mediated Delivery of Perylenediimide Guest Molecules. , 2010, Macromolecular rapid communications.

[27]  Theresa M. Allen,et al.  Determination of Doxorubicin Levels in Whole Tumor and Tumor Nuclei in Murine Breast Cancer Tumors , 2005, Clinical Cancer Research.

[28]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[29]  T. Weil,et al.  Cationized albumin-biocoatings for the immobilization of lipid vesicles , 2010, Biointerphases.

[30]  F. Farinati,et al.  Pegylated liposomal doxorubicin and gemcitabine in patients with advanced hepatocellular carcinoma , 2011, Cancer.

[31]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[32]  Christoph Peters,et al.  Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. , 2011, Nature nanotechnology.