The improved killing of both androgen-dependent and independent prostate cancer cells by etoposide loaded SPIONs coupled with NIR irradiation.

Etoposide (Eto) is a toxic drug that shows promise in treating prostate cancer (PCa) but confers significant side effects, and has poor solubility and bioavailability. Nanoparticles are quite successful in overcoming such problems. Multifunctional nanoparticles that provide an opportunity to perform combination therapy have attracted great interest in recent years. Superparamagnetic iron oxide nanoparticles (SPIONs) are popular in various biomedical applications, including magnetic resonance imaging, drug delivery, magnetic hyperthermia and recently in photothermal therapy, combining imaging with therapy. Here, for the enhanced killing of PCa cells that are either androgen-dependent or not, the combination of SPION based Eto delivery and mild hyperthermia triggered by laser irradiation is proposed for the first time in the literature. For the encapsulation of Eto, highly stable, small, polyacrylic acid coated SPIONs were conjugated with bovine serum albumin (BSA) (Eto-BSA@PAA@SPION). Eto-BSA@PAA@SPION with 9% drug content produced better chemotherapeutic outcomes than free Eto on both androgen-dependent/castration sensitive LNCaP and androgen-independent/castration-resistant PC3 and DU145 PCa cells by enhancing drug internalization. Single and short irradiation of Eto-BSA@PAA@SPION treated cells at 808 nm improved the drug release and sensitized cells for Eto, hence, increasing the toxicity dramatically in all studied PCa cell lines. Caspase-mediated apoptosis, DNA damage, and ROS generation were detected in the treated cells, increasing with the Eto dose and laser treatment. The IC50 for Eto is reduced to 0.08 µg mL-1, 0.13 µg mL-1 and 2.8 µg mL-1 with laser/Eto-BSA@PAA@SPION for LNCaP, DU145 and PC3 cells, respectively. These are the lowest IC50 values seen in the literature for Eto on these cell lines so far, suggesting that the demonstrated nanoparticles and treatment approaches have great potential to treat various PCa cells at low doses of the drug under mild laser treatment conditions.

Broad spectrum antibacterial photodynamic and photothermal therapy achieved with indocyanine green loaded SPIONs under near infrared irradiation.

Antimicrobial photodynamic therapy (aPDT) and antimicrobial photothermal therapy (aPTT) are promising local and effective alternative therapies for antibiotic resistant bacterial infections and biofilms. A combination of nanoparticles and organic photosensitizers offers a great opportunity to combine PDT and PTT for effective eradication of both planktonic bacteria and their biofilms. In this work, photo-induced antibacterial activity of indocyanine green (ICG), 3-aminopropylsilane coated superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) and ICG loaded APTMS@SPIONs was evaluated on planktonic cells and biofilms of Gram-negative (E. coli, K. pneumoniae, P. aeruginosa) and Gram-positive (S. epidermis) bacteria. A relatively low dose of ICG (25 µg mL-1) and SPIONs (0.425 µg mL-1 nanoparticle) in combination with single, short (10 min) laser irradiation at 808 nm with a power of 1150 mW was used in this study. No dark toxicity of the agents or antibacterial effect of the laser irradiation was observed. The charge of the particles did not provide a significant difference in their penetration to Gram-negative versus Gram-positive bacterial strains or their biofilms. APTMS@SPION/laser treatment completely eliminated P. aeruginosa and provided 7-log reduction in the colony forming unit (CFU) of E. Coli, but was not effective on the other two bacteria. This is the first example for antibacterial phototoxicity of this nanoparticle. ICG/laser and ICG-APTMS@SPION/laser treatments provided complete killing of all planktonic cells. Successful eradication of all biofilms was achieved with ICG/laser (3.2-3.7 log reduction in CFUs) or ICG-APTMS@SPION/laser treatment (3.3-4.4 log reduction in CFUs). However, an exceptionally high, 6.5-log reduction as well as a dramatic difference between ICG versus ICG/APTMS@SPION treatment was observed in K. pneumoniae biofilms with ICG-APTMS@SPION/laser treatment. Investigation of the ROS production and increase in the local temperature of the biofilms that were subjected to phototherapy suggested a combination of aPTT and aPDT mechanisms for phototoxicity, exhibiting a synergistic effect when ICG-APTMS@SPION/laser was used. This approach opens an exciting and novel avenue in the fight against drug resistant infections by successfully utilizing the antimicrobial and antibiofilm activity of low dose FDA approved optically traceable ICG and relatively low cost clinically acceptable iron oxide nanoparticles to enable effective aPDT/aPTT combination, induced via short-duration laser irradiation at a near-infrared wavelength.

Investigation of the factors affecting the photothermal therapy potential of small iron oxide nanoparticles over the 730-840 nm spectral region.

The use of superparamagnetic iron oxide nanoparticles (SPIONs) as a sensitizer in photothermal therapy (PTT) is relatively new and the origin of such a phenomenon is not known. Usually, large crystals and aggregated particles are preferred in the literature, suggesting that these increase the absorbance of particles at the irradiation wavelength, and hence, provide a larger temperature increase. This study has two major goals: identification of the key factors that affect the photo-induced temperature increase in well-controlled experiments and the influence of laser irradiation on nanoparticle properties. Small, biocompatible poly(acrylic acid) coated SPIONs (PAA/SPIONs) were used since they are more practical for future medical use than large aggregates. We studied the impact of three major laser-dependent variables, namely the wavelength (between 728 and 838 nm), intensity (1.85-9.76 W cm-2) and power (105-800 mW) as well as attenuation at the irradiation wavelength, on photothermal heating achieved with PAA/SPIONs. Within the studied range of these variables, only the laser power plays a critical role on the magnitude of photothermal heating in solutions. There is no strong correlation between the attenuation at the excitation wavelength and the temperature increase. In addition, extensive characterization of SPIONs before and after irradiation revealed no significant difference, which supports the re-usability of SPIONs. Lastly, the PTT potential of these small PAA/SPIONs was demonstrated in vitro on HeLa cells. At these low laser powers no temperature increase in SPION-free water or cell death in SPION-free cells was detected. Hence, this study provides a new insight into the photothermal effect of SPIONs, provides a clear and repeatable experimental procedure and demonstrates great potential for small SPIONs to be exploited in PTT.

One step emission tunable synthesis of PEG coated Ag2S NIR quantum dots and the development of receptor targeted drug delivery vehicles thereof.

PEGylation of quantum dots (QDs) to decrease their toxicity, increase blood circulation time, reduce non-specific uptake and also to solubilize and stabilize hydrophobic QDs in aqueous medium is a widely used approach and many different methods were developed to achieve this. QDs that are luminescent in the near-infrared region (NIR) have recently emerged as the more appropriate materials for bio-imaging studies. In this work, we describe a single step emission tunable aqueous synthesis of PEGylated Ag2S NIRQDs. They are highly cytocompatible, not only due to the PEG coating but also due to the intrinsic biocompatibility of Ag2S, and prepared in a single step aqueous method using thiolated PEGs as the only coating material. Tuning the emission wavelength within the medical window (775-930 nm) with a quantum yield between 2 and 65% is achieved by changing the reaction variables such as PEG molecular weight, pH and precursor ratios. Ag2S-PEG NIRQDs prepared from 5 kDa MPEG-SH at acidic pH provided a dramatic enhancement in the luminescence intensity. These NIRQDs were also designed with surface functional groups to attach folic acid and loaded with doxorubicin (DOX) which dramatically enhanced the uptake and efficacy of DOX (50% cell death with 15 nM DOX) in FA-receptor overexpressed cancer cell lines (HeLa). They also showed a strong cytoplasmic NIR signal in the in vitro studies, demonstrating great theranostic potential.

Anticancer use of nanoparticles as nucleic acid carriers.

Advances in nanotechnology opened up new horizons in the field of cancer research. Nanoparticles made of various organic and inorganic materials and with different optical, magnetic and physical characteristics have the potential to revolutionize the way we diagnose, treat and follow-up cancers. Importantly, designs that might allow tumor-specific targeting and lesser side effects may be produced. Nanoparticles may be tailored to carry conventional chemotherapeutics or new generation organic drugs. Currently, most of the drugs that are commonly used, are small chemical molecules targeting disease-related enzymes. Recent progress in RNA interference technologies showed that, even proteins that are considered to be "undruggable" by small chemical molecules, might be targeted by small RNAs for the purpose of curing diseases, including cancer. In fact, small RNAs such as siRNAs, shRNAs and miRNAs can drastically change cellular levels of almost any given disease-associated protein or protein group, resulting in a therapeutic effect. Gene therapy attempts were failing mainly due to delivery viral vector-related side effects. Biocompatible, non-toxic and efficient nanoparticle carriers raise new hopes for the gene therapy of cancer. In this review article, we discuss new advances in nucleic acid and especially RNA carrier nanoparticles, and summarize recent progress about their use in cancer therapy.