Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.

Near infrared (NIR)-absorbing noble metal nanostructures are being extensively studied as theranostic agents, in particular for photoacoustic imaging and photothermal therapy. Because of the electric field enhancement at the tips of anisotropic metal nanostructures, positioning photoactive species at these sites can lead to increased energy absorption. Herein, we show the site-specific placement of NIR-active photosensitizers at the ends of gold nanorods (AuNRs) by growing porous TiO caps. The surface plasmon resonance of the AuNRs was carefully tuned to overlap with the exciton absorption of indocyanine green (ICG), a NIR photosensitizer with low quantum yields and poor photostability. In conjugating high amounts of ICG to the TiO caps, increased amounts of singlet oxygen (O) were generated as compared to when ICG was attached to sidewalls of the AuNRs. Because the AuNRs also cause local increases in temperature upon NIR excitation, DNA strands were next attached to the AuNRs sidewalls and loaded with doxorubicin (DOX). We found that the synergistic effect of increased O and photothermal-induced drug delivery led to significant improvements in tumor cell killing. This work demonstrates that with careful design over hybrid nanostructure synthesis, higher levels of tumor therapy may be achieved.

We illustrate how intermolecular interactions facilitate ATP-free electron transfer between either native or engineered MoFe protein (MoFeP) from nitrogenase and a CdS nanorod (NR) by following the reduction of H+ to H2. First, by varying the charge on the surface of the NR, we show the role of electrostatic interactions on MoFeP binding to the particle surface and subsequent H+ reduction. Next, the role of strong, semicovalent thiol–CdS interactions was tested using free cysteines on the MoFeP. By blocking free cysteines, we show that the presence of free thiols on the protein has little to no influence on CdS binding and resultant photocatalytic activity. We next studied methods to covalently bind the protein to CdS by modifying the free cysteines with dibenzocyclooctyne (DBCO) and reacting the CdS NRs capped with a mixture of negatively charged thioglycolic acid and thiol-PEG3-azide ligands. As compared to that of the unmodified proteins, a 32.2 ± 1.5% and 61.7 ± 2.1% increase in H2 production was observed from MoFeP and C-MoFeP, respectively. At last, to test the effect of both charge and covalent tethering, positively charged cysteamine/azide CdS NRs were reacted with DBCO-modified C-MoFeP, which showed little improvement over native C-MoFeP alone under irradiation. These results show the importance of both electrostatic associations between the NR and protein and covalently tethering the protein to the semiconductor surface for enhanced electron transfer and photodriven activity.

In this work, we show that a prodrug enzyme covalently photoconjugated to live cell receptors survives endosomal proteolysis and retains its catalytic activity over multiple days. Here, a fusion protein was designed with both an antiepidermal growth factor receptor (EGFR) affibody and the prodrug enzyme cytosine deaminase, which can convert prodrug 5-fluorocytosine to the anticancer drug 5-fluorouracil. A benzophenone group was added at a site-specific mutation within the affibody, and the fusion protein was selectively photoconjugated to EGFR receptors expressed on membranes of MDA-MB-468 breast cancer cells. The fusion protein was next labeled with two dyes for tracking uptake: AlexaFluor 488 and pH-sensitive pHAb. Flow cytometry showed that fusion proteins photo-cross-linked to EGFR first underwent receptor-mediated endocytosis within 12 h, followed by recycling back to the cell membrane within 24 h. These findings were also confirmed by confocal microscopy. The unique cross-linking of the affibody-enzyme fusion proteins was utilized for two anticancer treatments. First, the covalent linking of the protein to the EGFR led to inhibition of ERK signaling over a two-day period, whereas conventional antibody therapy only led to 6 h of inhibition. Second, when the affibody-CodA fusion proteins were photo-cross-linked to EGFR overexpressed on MDA-MB-468 breast cancer cells, prodrug conversion was found even 48 h postincubation without any apparent decrease in cell killing, while without photo-cross-linking no cell killing was observed 8 h postincubation. These studies show that affinity-mediated covalent conjugation of the affibody-enzymes to cell receptors allows for prolonged expression on membranes and retained enzymatic activity without genetic engineering.

A method to synthesize BiVO 4 nanoparticles and nanorods hydrothermally using sodium oleate as a capping ligand is presented. The BiVO 4 nanocrystals possessed the expected blue shift in absorbance relative to bulk that occurs with scaling of particle size. Next, we transferred the BiVO 4 nanoparticles from organic solvents to water using two different ligands. These particles were tested as water oxidation and dye reduction catalysts.Extensive research has recently focused on discovering new solid state catalysts that can effectively split water using either externally biased 1-5 or unbiased electrodes. 6-17 While wide-band gap semiconductors like TiO 2 (ref. 11) and WO 3 (ref. 16, 18 and 19) have been studied as photocatalysts for water-splitting, more recent efforts have turned to BiVO 4 due to its bandgap of 2.4 eV and ability to absorb in the visible. 1,20 In the presence of electron scavengers such as AgNO 3 or NaIO 3 , BiVO 4 has also shown a strong ability to oxidize water and generate oxygen. Typically, BiVO 4 has been grown by chemical vapor deposition (CVD) 21,22 or chemical bath deposition (CBD) 23 on conductive surfaces, which has produced roughly structured, high surface area photoactive electrodes. In other work, BiVO 4 photocatalysts have been obtained by reacting potassium vanadate powder with Bi(NO 3 ) 3 to yield nanoclusters that showed 9% quantum efficiency (at 450 nm) as determined by the amount of oxygen generated under photoirradiation. 24 Amorphous shaped BiVO 4 -Ru/SrTiO 3 :Rh (ref. 9) or BiVO 4 /graphene/SrTiO 3 (ref. 7) composites have also been synthesized to run complete water splitting to oxygen and hydrogen under visible light. Furthermore, Li and co-workers recently used micron sized M/MnO x / BiVO 4 and M/Co 3 O 4 /BiVO 4 (M is a noble metal) composites to split water into oxygen and reduce methyl orange dye or NaIO 3 . 25,26 The co-catalysts in this case were selectively deposited by photoreduction or oxidation of Pt or MnO x nanocrystals respectively on different facets of the BiVO 4 structures, which led to better charge separation and lower back reactivities. More recently, co-catalysts like Co 3 O 4 , FeOOH and NiOOH were also electrodeposited on BiVO 4 electrodes for improved water oxidation under illumination. 27 In order to improve catalytic performance, various BiVO 4 architectures have also been doped with low amounts ($0.5-5%) of metals such as tungsten, 28,29 molybdenum 2 and phosphate 30 which allow better hole transport and enhanced water oxidation abilities. Recently, published work by Yang and coworkers showed an elegent and straightforward method to assemble BiVO 4 wires with Rh-SrTiO 3 to achieve water splitting. 31 Despite these successes in producing photoactive BiVO 4 however, the synthesis of well-dened nanostructures of BiVO 4 with control over both size and shape has remained challenging. Although a recent report showed successful hydrogen generation by nanosized BiVO 4 in water presumably due to the change in energy levels as compared to bulk, the size ...