Co-precipitation Synthesis of Near-infrared Iron Oxide Nanocrystals on Magnetically Targeted Imaging and Photothermal Cancer Therapy via Photoablative Protein Denature.

Near-infrared (NIR)-based nanomaterials that provide efficient tumor ablation for cancer therapy have been reported. However, the issues of biocompatibility of metals or ions in inorganic nanoparticles systems such as copper and gold nanoparticles are still a matter of concern. In this study, we developed a facile and ligand-assisted co-precipitation method to synthesize biocompatible iron oxide (IO) nanocrystals with NIR absorption that provided T2-weighted magnetic resonance (MR) images and photothermal ablation characteristics suitable for cancer theranostics. Our results showed that 150-nm particles can be synthesized and optimized by using different amounts of ligand. NIR-IO nanocrystals of this size showed high photothermal conversion efficiency (21.2%) and T2-weighted MR contrast (transverse relaxivity value approximately 141 S-1 mM-1). The NIR-IO nanocrystals showed no cytotoxicity in HT-29 colorectal cancer cells without irradiation, whereas the viability of cells that received NIR-IO nanocrystals decreased significantly after 808-nm laser irradiation. The mechanism of cell death may involve alterations in protein secondary structure and membrane permeability. For in vivo studies, 4-fold enhanced tumor accumulation was significantly observed of NIR-IO nanocrystals with a magnetic field (MF) application, resulting in a 3-fold higher T2-weighted MR signal than that produced by a commercial T2-weighted MR contrast agent (Resovist®) and excellent photothermal efficacy (approximately 53 °C) for cancer treatment. The innovative NIR-IO nanocrystals showed excellent biocompatibility and have great potential as a theranostic agent against cancer.

Encapsulation of Au/Fe3O4 nanoparticles into a polymer nanoarchitecture with combined near infrared-triggered chemo-photothermal therapy based on intracellular secondary protein understanding.

The combination of the functions of near infrared-triggered molecule release and chemo-photothermal therapy improved the therapeutic effect, but clarification of the cancer damage pathway in terms of protein molecule levels has yet to be well studied. In this study, we developed a polymer encapsulation synthesis of Au/Fe3O4@polymer nanoparticles as a Swiss army knife to integrate near infrared absorption, magnetism, and doxorubicin (DOX) loading ability into a single package. By exposing to near infrared absorption, the Au/Fe3O4@polymer nanoparticles possessed photothermal therapy, exhibiting anti-tumor growth suppression of HT-29 tumor-bearing nude mice with less body weight loss. To deeply understand the interactions between the drug-loaded nanocarriers and the protein structures of the treated cells, delivering therapeutic DOX agent combined with photothermal therapy with Au/Fe3O4@polymer nanostructures to cancer cells was investigated. Synchrotron-based FTIR imaging and confocal imaging showed direct observation of the efficient photo-chemotherapy impacting MCF7, MCF7/ADR, and HT-29 cells after the near infrared radiation-triggered DOX release. Our demonstration outlines how the cell destruction in the molecular mechanism was initiated by chemo-photothermal combination therapy after the translocation of DOX from the cytosol to the nuclei, leading to altered intracellular secondary proteins. For preclinical application of potential diagnosis to cancer cells, Au/Fe3O4@polymer nanoparticles performed integrated computed tomography/magnetic resonance imaging contrast enhancement and near infrared-triggered chemo-photothermal therapy.

Metal nanobullets for multidrug resistant bacteria and biofilms.

Infectious diseases were one of the major causes of mortality until now because drug-resistant bacteria have arisen under broad use and abuse of antibacterial drugs. These multidrug-resistant bacteria pose a major challenge to the effective control of bacterial infections and this threat has prompted the development of alternative strategies to treat bacterial diseases. Recently, use of metallic nanoparticles (NPs) as antibacterial agents is one of the promising strategies against bacterial drug resistance. This review first describes mechanisms of bacterial drug resistance and then focuses on the properties and applications of metallic NPs as antibiotic agents to deal with antibiotic-sensitive and -resistant bacteria. We also provide an overview of metallic NPs as bactericidal agents combating antibiotic-resistant bacteria and their potential in vivo toxicology for further drug development.

Improved photodynamic cancer treatment by folate-conjugated polymeric micelles in a KB xenografted animal model.

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta-tetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed. In this work, a folate-conjugated polymeric m-THPC delivery system is developed for improving tumor targeting of the photosensitizer, preventing photodamage to the healthy tissue, and increasing the effectiveness of the photosensitizers. The results demonstrate that folate-conjugated m-THPC-loaded micelles with particle sizes around 100 nm are taken up and accumulated by folate receptor-overexpressed KB cells in vitro and in vivo, and their PDT has no significant adverse effects on the body weight of mice. After an extended delivery time, a single dose of folate-conjugated m-THPC-loaded micelles has higher antitumor effects (tumor growth inhibition = 92%) through inhibition of cell proliferation and reduction of vessel density than free m-THPC or m-THPC-loaded micelles at an equivalent m-THPC concentration of 0.3 mg kg(-1) after irradiation. Furthermore, folate-conjugated m-THPC-loaded micelles at only 0.2 mg kg(-1) m-THPC have a similar antitumor efficacy to m-THPC or m-THPC-loaded micelles with the m-THPC concentration at 0.3 mg kg(-1) , which indicates that the folate conjugation on the micellar photosensitizer apparently reduces the requirement of m-THPC for PDT. Thus, folate-conjugated m-THPC-loaded micelles with improved selectivity via folate-folate receptor interactions have the potential to reduce, not only the skin photosensitivity, but also the drug dose requirement for clinical PDT.

Dendrimer phthalocyanine-encapsulated polymeric micelle-mediated photochemical internalization extends the efficacy of photodynamic therapy and overcomes drug-resistance in vivo.

Clinically, the efficacy of chemotherapeutic agents can be dramatically reduced in cancer cells with multiple drug resistance (MDR). In doxorubicin-resistant breast cancer cells, drugs accumulate only within discrete cytosolic organelles that abrogate their therapeutic effects in vitro and in vivo. Photochemical internalization (PCI), a specific branch of photodynamic therapy (PDT), is a novel strategy utilized for the site-specific triggered drug/gene release. The objective of this study was to evaluate the nanoparticle-based PDT/PCI effects on the reversal of drug resistance. Dendrimer phthalocyanine-encapsulated polymeric micelle (DPc/m)-mediated PCI, combined with doxorubicin, was studied in drug-resistant MCF-7 cells and a xenograft model. Our results show that the internalized DPc/m showed unique PCI properties inside the cells and thereby facilitating doxorubicin release from the endo-lysosomes to nuclei after photoirradiation. Moreover, 'light before' PCI showed the highest antitumor efficacy and the depth of the proliferating cell nuclear antigen-negative area in tumor sections after DPc/m-mediated PDT was obviously increased by combination therapy with doxorubicin; this indicates the limitation of depth of light penetration in PDT, which may be improved by PCI. We conclude that nanotechnology-based PCI possesses several clinical benefits, such as overcoming drug resistance and treating deeper lesions that are intractable by PDT alone.

Poly(L-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells.

Multiple drug resistance (MDR) seriously reduces the efficacy of many chemotherapeutic agents for cancer. P-Glycoprotein, an efflux pump overexpressed on the cell surface, plays an important role in drug resistance, but several surfactants, such as vitamin E TPGS, can inhibit P-glycoprotein. In this study, a polylactide-surfactant block copolymer poly(l-lactide)-vitamin E TPGS (PLA-TPGS) was synthesized using bidentate sulfonamide zinc ethyl complex as an efficient catalyst, and its self-assembled nanoparticles were used as carriers of doxorubicin. We first found that the activity of P-glycoprotein in drug-resistant breast cancer MCF-7/ADR cells was decreased after incubation with PLA-TPGS nanoparticles. In addition, the nuclear accumulation and cytotoxicity of doxorubicin were significantly increased by encapsulation into the nanoparticles. The enhanced efficacy of the doxorubicin-loaded PLA-TPGS nanoparticles may result from the combination of inhibition of efflux and increased entry of doxorubicin into the nucleus in drug-resistant MCF-7/ADR cells. Therefore, this innovative delivery system has potential to act as a nanomedicine for therapy of both drug-sensitive and drug-resistant cancer.