The development of non-toxic theranostic nanoparticles capable of delivering a therapeutic cargo and providing a means for diagnosis is one of the most challenging tasks in nano-biotechnology. Gene therapy is a very important mode of therapy and polyethyleneimine (PEI) is one of the most successful vehicles for gene transfection, yet poses significant toxicity. Optical imaging utilizing quantum dots is one of the newer but fast growing diagnostic modalities, which requires non-toxic, highly luminescent materials, preferentially active in the near infrared region. Ag2S NIRQDs fit to this profile perfectly. Here, we demonstrate the aqueous synthesis of cationic Ag2S NIRQDs with a mixed coating of 2-mercaptopropionic acid (2MPA) and PEI (branched, 25 kDa), which are highly luminescent in the NIR-I window (λem = 810-840 nm) as new theranostic nanoparticles. Synergistic stabilization of the QD surface via the simultaneous use of a small molecule and a polymeric material provided the highest quantum yield, 150% (with respect to LDS 798 at pH 7.4), reported in the literature for Ag2S. These cationic particles show a dramatic improvement in cytocompatibility even without PEGylation, a strong optical signal easily detected by confocal laser microscopy and effective conjugation and transfection of the green fluorescence protein plasmid (pGFP) to HeLa and MCF-7 cell lines (40% efficiency). Overall, these Ag2S NIRQDs show great potential as new theranostics.

Nanoscale metal-organic frameworks (NMOFs) are an interesting and unique class of hybrid porous materials constructed by the self-assembly of metal ions/clusters with organic linkers. The high storage capacities, facile synthesis,...

Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal−organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies.

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) 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.