• HA-coated nanocarriers
• hyaluronic acid
• tumor-targeting delivery nanocarriers

• PLGA
• cytotoxicity
• docetaxel
• nanoparticle
• polymer
• prostate cancer

• breast cancer
• multidrug resistance
• nanoparticle
• receptor-mediated
• surface-modification
• targeted delivery

• FP-119-43 Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, Saudi Arabia

• antibody conjugated
• antibody drug conjugate nanoparticles
• antibody drug conjugates
• breast cancer
• polymeric nanoparticles

• antibody conjugate nanoparticles
• antibody drug conjugates
• breast cancer
• nanomedicines
• targeted delivery systems

• Animals
• Antineoplastic Agents, Immunological/administration & dosage
• Antineoplastic Agents, Immunological/chemistry
• Antineoplastic Agents, Immunological/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/immunology
• Drug Carriers/administration & dosage
• Drug Carriers/chemistry
• Drug Delivery Systems/methods
• Female
• Humans
• Immunoconjugates/administration & dosage
• Immunoconjugates/chemistry
• Immunoconjugates/pharmacology
• Liposomes/administration & dosage
• Liposomes/chemistry
• Liposomes/immunology
• Nanoparticles/administration & dosage
• Nanoparticles/chemistry
• Polymers/chemistry

• CTQ2017-84131-R and CTQ2016-81797-REDC Programa Redes Consolider Ministerio de Ciencia e Innovación, Spain
• PI16/01121 Instituto de Salud Carlos III

Background: Multimodal imaging probes have become a powerful tool for improving detection sensitivity and accuracy, which are important in disease diagnosis and treatment.

Methods: In this study, novel bifunctional magnetic resonance imaging (MRI)/fluorescence probes were prepared by loading gadodiamide into fluorescent silica nanoparticles (NPs) (Gd@Cy5.5@SiO₂-PEG-Ab NPs) for targeting of prostate cancer (PCa). The physicochemical characteristics, biosafety and PCa cell targeting ability of the Gd@Cy5.5@SiO₂-PEG-Ab NPs were studied in vitro and in vivo.

Results: The Gd@Cy5.5@SiO₂-PEG-Ab NPs had a spherical morphology with a relatively uniform size distribution and demonstrated high efficiency for Gd loading. In vitro and in vivo cell-targeting experiments demonstrated a high potential for the synthesized NPs to target prostate-specific membrane antigen (PSMA) receptor-positive PCa cells, enabling MRI and fluorescence imaging. In vitro cytotoxicity assays and in vivo hematological and pathological assays showed that the prepared NPs exhibited good biological safety.

Conclusion: Our study demonstrates that the synthesized Gd@Cy5.5@SiO₂-PEG-Ab NPs have great potential as MRI/fluorescence contrast agents for specific identification of PSMA receptor-positive PCa cells.

• fluorescence imaging
• magnetic resonance imaging
• prostate cancer
• silica nanoparticles
• targeting

Purpose: To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. Methods: Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing HER2 at much lower levels and non-tumorigenic (D492), were cultured in the presence of polystyrene microparticles of 1 µm in diameter, biofunctionalized with either a specific anti-HER2 antibody or a non-specific secondary antibody. Mono- and cocultures of both cell lines in static and fluidic conditions were performed, and the cells with internalized microparticles were scored. Results: Globally, the D492 cell line showed a higher endocytic capacity than the D492HER2 cell line. Microparticles that were functionalized with the anti-HER2 antibody were internalized by a higher percentage of cells than microparticles functionalized with the non-specific secondary antibody. Although internalization was reduced in fluidic culture conditions in comparison with static conditions, the increase in the internalization of microparticles biofunctionalized with the anti-HER2 antibody was higher for the cell line overexpressing HER2. Conclusion: The biofunctionalization of microparticles with a specific targeting molecule remarkably increases their internalization by cells in fluidic culture conditions (simulating the blood stream). This result emphasizes the importance of targeting for future in vivo delivery of drugs and bioactive molecules through microparticles.

• HER2
• biofunctionalization
• coculture
• microfluidics
• polystyrene µPs

• Breast cancer therapy
• Chitosan nanoparticles
• Docetaxel
• IGF-1R siRNA
• MUC1 aptamer

• Aptamer
• Chitosan
• Docetaxel
• Metastatic breast cancer
• cMET siRNA

• H2020 European Research Council
• Royal Society
• Royal Academy of Engineering
• Engineering and Physical Sciences Research Council

Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs.

• biodistribution
• docetaxel
• emulsification solvent evaporation
• pharmacokinetics
• poly(lactide-co-glycolide)
• poly(lactide-co-glycolide)-poly(ethylene glycol)
• polymeric nanoparticles
• sustained release

This study evaluated rituximab-conjugated, doxorubicin-loaded microbubbles (RDMs) in combination with ultrasound as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Rituximab, a monoclonal CD20 antibody, was attached to the surfaces of doxorubicin-loaded microbubbles. RDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of RDMs in combination with ultrasound (RDMs+US) were evaluated in vitro in CD20+ and CD20– cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20–) lymphoma cell-grafted mice. RDMs specifically bound to CD20+ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via ultrasound. RDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (P<0.05). RDMs+US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments (P<0.05). Our results showed that RDMs+US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20+ B cell lymphoma growth in vivo. Targeted RDMs could be employed as ultrasound molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with ultrasound for CD20+ B cell malignancy treatment.

• B cell lymphoma
• microbubble
• rituximab
• theranostics
• ultrasound

siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated.

It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells.

This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1-overexpressing tumor cells.

• HER2+ breast cancer
• cancer nanomedicine
• mesoporous silica nanoparticles
• siRNA

• HHSN261201300078C NCI NIH HHS
• R01 GM089918 NIGMS NIH HHS
• R41 DK094571 NIDDK NIH HHS
• U54 CA112970 NCI NIH HHS

The objective of this study was the synthesis of folic acid- (FA-) targeted polymeric micelles of Synperonic PE/F 127-cholesteryl hemisuccinate (PF127-Chol) for specific delivery of docetaxel (DTX). Targeted or nontargeted micelles loaded with DTX were prepared via dialysis method. The effects of processing variables on the physicochemical properties of targeted micelles were evaluated using a full factorial design. After the optimization of the polymer/drug ratio, the organic solvent type used for the preparation of the micelles, and the temperature of dialyzing medium, the in vitro cytotoxicity and cellular uptake of the optimized micelles were studied on B16F10 melanoma cells by flow cytometry and fluorescent microscopy. The anticancer efficacy of DTX-loaded FA-PF127-Chol was evaluated in mice bearing melanoma tumor. Optimized targeted micelles had the particle size of 171.3 nm, zeta potential of −7.8 mV, PDI of 0.325, and a high encapsulation efficiency that released the drug within 144 h. The MTT assay indicated that targeted micelles carrying DTX were significantly more cytotoxic, had higher cellular uptake, and reduced the tumor volume significantly more than the nontargeted micelles and the free drug. FA-PF127-Chol could be, therefore, a promising biomaterial for tumors overexpressing folate receptors.

About 30% of human breast cancers are human epidermal growth factor receptor 2 (HER2)⁺. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2⁺ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clinical outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the development of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional compartimentalization, which allows to combine the specific target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photothermal ablation or in photodynamic therapy have been functionalized in order to match specificity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2⁺ breast cancer and anti-HER2 therapy, in particular deepening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2⁺ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical practice; however promising results encourage an upcoming translation of this research for the next future.

• Human epidermal growth factor receptor 2
• Human epidermal growth factor receptor 2⁺-breast cancer
• Nanomedicine
• Nanoparticle
• Targeted-therapy

• Anti-tumor
• Box-Behnken
• Docetaxel
• Experimental design
• Nanoparticles
• PLGA
• Pegylation

• functionality
• nanoparticles
• nanoparticulate dosage forms
• polylactide-co-glycolide

The purpose of this study was to prepare pegylated poly lactide-co-glycolide (PEG-PLGA) nanoparticles (NPs) loaded with roxithromycin (RXN) with appropriate physicochemical properties and antibacterial activity. Roxithromycin, a semi-synthetic derivative of erythromycin, is more stable than erythromycin under acidic conditions and exhibits improved clinical effects.

RXN was loaded in pegylated PLGA NPs in different drug;polymer ratios by solvent evaporation technique and characterized for their size and size distribution, surface charge, surface morphology, drug loading, in vitro drug release profile, and in vitro antibacterial effects on S. aureus, B. subtilis, and S. epidermidis.

NPs were spherical with a relatively mono-dispersed size distribution. The particle size of nanoparticles ranged from 150 to 200 nm. NPs with entrapment efficiency of up to 80.0±6.5% and drug loading of up to 13.0±1.0% were prepared. In vitro release study showed an early burst release of about 50.03±0.99% at 6.5 h and then a slow and steady release of RXN was observed after the burst release. In vitro antibacterial effects determined that the minimal inhibitory concentration (MIC) of RXN loaded PEG-PLGA NPs were 9 times lower on S. aureus, 4.5 times lower on B. subtilis, and 4.5 times lower on S. epidermidis compared to RXN solution. In conclusion it was shown that polymeric NPs enhanced the antibacterial efficacy of RXN substantially.

In the recent years, there is an increasing attention to the using of Fe₃O₄ magnetite nanoparticles (MNPs) as drug delivery systems. Application of this nanoparticles could profit advantages of nanomedicine to enhance biological activity of pharmaceutical ingredients.

Fe₃O₄ MNPs were synthesised by a chemical method and characterized by transmission electron microscopy and energy-dispersive spectroscopy techniques. In the next step, docetaxel-coated Fe₃O₄ MNPs were prepared, using percipitation method. The surface chemistry of docetaxel-coated Fe₃O₄ MNPs as well as their thermal decomposition characteristics were examined using fourier transform infrared spectroscopy and thermogravimetric analyzer equipment, respectively. The cytotoxicity assay was conducted on 4 T1 breast cancer carsinoma by MTT assay to evaluate the possible in vitro antiproliferative effects of docetaxel-coated Fe₃O₄ MNPs.

During precipitation process, docetaxel molecules were precipitated on the surface of Fe₃O₄ MNPs by the ratio of 3:100 w/w which indicates that each milligram of coated Fe₃O₄ MNPs averagely contained 30 μg pure docetaxel compound. Docetaxel showed aniproliferative effects against mentioned cell line. The higestest concentartion of docetaxel (80 μg/ml) caused about 80% cell death. However, the results demostarted that much lower amounts of docetaxel will be needed in combination of Fe₃O₄ MNPs to produce the potent antiproliferative effect compared to docetaxel alone. Dose response cytotoxicity assay of docetaxel-coated Fe₃O₄ MNPs against 4 T1 breast cancer cells showed that lower amount of docetaxel (0.6 μg/ml) can exhibit higher cytotoxic effect against this cancer cell line (90% cell death).