• Indocyanine green (ICG)
• Niosome
• lycopene
• prostate cancer

• DARPin
• gold nanorods
• molecular dynamic simulations
• near-infrared illumination
• tumor cells

• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Breast Neoplasms/therapy
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Gold/chemistry
• Gold/pharmacology
• Humans
• Metal Nanoparticles/chemistry
• Metal Nanoparticles/therapeutic use
• Nanotubes/chemistry
• Phototherapy
• Receptor, ErbB-2/metabolism

• Fondazione per la Ricerca Biomedica
• Seventh Framework Programme
• Ministero dell’Istruzione, dell’Università e della Ricerca

A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h.

Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model.

LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.

The online version of this article (10.1186/s12951-019-0457-3) contains supplementary material, which is available to authorized users.

• Curcumin
• Doxorubicin
• Drug delivery
• Herceptin
• Lipo-PEG-PEI complex

• Cancer therapy
• Drug delivery
• Heat mediator
• Hyperthermia
• Magnetic nanoparticle

• ADCC
• HER2-positive breast cancer
• biocompatible nanoparticles
• chemotherapy
• immunotherapy
• nanodrug

• Antibodies, Bispecific/chemistry
• Antibodies, Bispecific/pharmacology
• Antibodies, Neoplasm/chemistry
• Antibodies, Neoplasm/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Cotinine/chemistry
• Dextrans/chemistry
• Dextrans/pharmacology
• Female
• Humans
• MCF-7 Cells
• Nanotubes, Carbon/chemistry
• Receptor, ErbB-2/antagonists & inhibitors
• Receptor, ErbB-2/metabolism

Superparamagnetic iron oxide nanoparticles (MNP) offer several advantages for applications in biomedical and biotechnological research. In particular, MNP-based immobilization of enzymes allows high surface-to-volume ratio, good dispersibility, easy separation of enzymes from the reaction mixture, and reuse by applying an external magnetic field. In a biotechnological perspective, extremophilic enzymes hold great promise as they often can be used under non-conventional harsh conditions, which may result in substrate transformations that are not achievable with normal enzymes. This prompted us to investigate the effect of MNP bioconjugation on the catalytic properties of a thermostable carboxypeptidase from the hyperthermophilic archaeon Sulfolobus solfataricus (CPSso), which exhibits catalytic properties that are useful in synthetic processes.

CPSso was immobilized onto silica-coated iron oxide nanoparticles via NiNTA-His tag site-directed conjugation. Following the immobilization, CPSso acquired distinctly higher long-term stability at room temperature compared to the free native enzyme, which, in contrast, underwent extensive inactivation after 72 h incubation, thus suggesting a potential utilization of this enzyme under low energy consumption. Moreover, CPSso conjugation also resulted in a significantly higher stability in organic solvents at 40°C, which made it possible to synthesize N-blocked amino acids in remarkably higher yields compared to those of free enzyme.

The nanobioconjugate of CPSso immobilized on silica-coated magnetic nanoparticles exhibited enhanced stability in aqueous media at room temperature as well as in different organic solvents. The improved stability in ethanol paves the way to possible applications of immobilized CPSso, in particular as a biocatalyst for the synthesis of N-blocked amino acids. Another potential application might be amino acid racemate resolution, a critical and expensive step in chemical synthesis.

• bioconjugation
• colloidal nanoparticles
• drug delivery systems
• nanomedicine
• nanoparticle-cell interactions

• ligand orientation
• nanoparticles
• tailoring
• targeting
• tumor

• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/chemistry
• Bacillus subtilis/drug effects
• Barbiturates/administration & dosage
• Barbiturates/chemistry
• Escherichia coli/drug effects
• Humans
• Magnetite Nanoparticles/administration & dosage
• Magnetite Nanoparticles/chemistry
• Pseudomonas aeruginosa/drug effects
• Silicon Dioxide/administration & dosage
• Silicon Dioxide/chemistry
• Spectroscopy, Fourier Transform Infrared
• Staphylococcus aureus/drug effects

Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid) and surface-functionalized with anticarcinoembryonic antigen (anti-CEA) and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC) cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF) sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T) and a low-CEA expressing cell line (HCT116). Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter), dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm) and the zeta-potential (−38 mV) of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS) was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm⁻¹, absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116) confirm that the as-prepared MF-anti- CEA is highly specific for CEA-expressing cells. Finally, transmission electron microscopy analyses show that the association with anti-CEA seems to increase the number of LS174T cells with internalized maghemite nanoparticles, whereas no such increase seems to occur in the HCT116 cell line. In conclusion, the MF-anti-CEA sample is a biocompatible device that can specifically target CEA, suggesting its potential use as a theragnostic tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.

• Raman
• anti-CEA antibody
• biocompatible device
• diagnostic
• magnetic nanoparticles
• targeted delivery

• cancer
• drug-delivery systems
• nanomedicine
• patient-friendly