A key attribute of drug delivery systems (DDSs) is their ability to regulate drug release, minimizing side effects and improving therapeutic efficacy of conventional pharmaceuticals. 1 Two approaches can be used to regulate the release of the therapeutic payload from the carrier: endogenous and exogenous activation. Endogenous activation strategies 2 exploit specific physiochemical characteristics of the pathological microenvironment, providing biologicallycontrolled release. Exogenous activation 3 provides a complementary approach, employing orthogonal external stimuli to effect drug release.Light provides a highly orthogonal external stimulus, allowing spatiotemporal control of payload release. In a recent applications of this strategy, drug encapsulated carriers of 100-500nm size (i.e. mesoporous silica, self-assembled molecular aggregates) containing a photo switch for cargo release has been developed. 4 In an alternative approach, caged drugs have been developed where the activity of the drug is suppressed by attaching it to a blocking element through a photoremovable protecting group. 5Monolayer protected gold nanoparticls (AuNPs) provide an appealing synthetic scaffold for the creation of DDSs due to their functional versatility, better biocompatibility, and low toxicity. 6 Moreover, through appropriate choice of particle size (2-10 nm), enhanced biodistribution (i.e. passive targeting) can be obtained through the enhanced permeation and retention (EPR) effect. 7 The EPR effect arises from the increased permeability of the tumor tissue vasculature, which allows nanocarriers to extravasate into the interstitial space, 1, 7 resulting in an enrichment of the carriers within the tumor tissue. We describe here the use of AuNPs for photocontrolled release of a caged anticancer drug (5-fluorouracil, 5-FU) by conjugating the drug to the particle surface through a photoresponsive o-nitrobenzyl (ONB) linkage. In this approach, the particle serves both to cage and transport the therapeutic.The fluorouracil conjugated gold nanoparticles (Au_PCFU) synthesized for this study possess a gold core diameter of ~2-nm and feature a surface functionality comprising of a mixed selfassembled monolayer of photocleavable and zwitterionic thiol ligands. The two ligands feature a common basic structure, where an alkyl segment is used to confer stability on the particle, while the tetra(ethylene glycol) component provides water solubility and superior biocompatibility. 8, 6d The zwitterionic ligand serves to enhance solubility and prevent cellular uptake, 9 while the photocleavable ligand integrates fluorouracil (5-FU) moieties to the nanoparticle surface through a terminally anchored orthonitrobenzyl (ONB) group. The ONB group has long term stability under ambient light in biological environments. However, it E-mail: rotello@chem.umass.edu. Supporting Information Available: Synthesis of ligands, preparation of the nanoparticle, protocols for in vitro and cellular studies, and other experimental procedures. This information is avail...

Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior. The NPSCs are ~130 nm in diameter and feature low toxicity and excellent stability in serum. The effectiveness of these NPSCs as therapeutic protein carriers was demonstrated through the delivery of fully functional caspase-3 to HeLa cells with concomitant apoptosis. Analogous delivery of green fluorescent protein (GFP) confirmed cytosolic delivery as well as intracellular targeting of the delivered protein, demonstrating the utility of the system for both therapeutic and imaging applications.

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BackgroundThere is worldwide interest in silver nanoparticles (AgNPs) synthesized by various chemical reactions for use in applications exploiting their antibacterial activity, even though these processes exhibit a broad range of toxicity in vertebrates and invertebrates alike. To avoid the chemical toxicity, biosynthesis (green synthesis) of metal nanoparticles is proposed as a cost-effective and environmental friendly alternative. Aloe vera leaf extract is a medicinal agent with multiple properties including an antibacterial effect. Moreover the constituents of aloe vera leaves include lignin, hemicellulose, and pectins which can be used in the reduction of silver ions to produce as AgNPs@aloe vera (AgNPs@AV) with antibacterial activity.MethodsAgNPs were prepared by an eco-friendly hydrothermal method using an aloe vera plant extract solution as both a reducing and stabilizing agent. AgNPs@AV were characterized using XRD and SEM. Additionally, an agar well diffusion method was used to screen for antimicrobial activity. MIC and MBC were used to correlate the concentration of AgNPs@AV its bactericidal effect. SEM was used to investigate bacterial inactivation. Then the toxicity with human cells was investigated using an MTT assay.ResultsThe synthesized AgNPs were crystalline with sizes of 70.70 ± 22-192.02 ± 53 nm as revealed using XRD and SEM. The sizes of AgNPs can be varied through alteration of times and temperatures used in their synthesis. These AgNPs were investigated for potential use as an antibacterial agent to inhibit pathogenic bacteria. Their antibacterial activity was tested on S. epidermidis and P. aeruginosa. The results showed that AgNPs had a high antibacterial which depended on their synthesis conditions, particularly when processed at 100 oC for 6 h and 200 oC for 12 h. The cytotoxicity of AgNPs was determined using human PBMCs revealing no obvious cytotoxicity. These results indicated that AgNPs@AV can be effectively utilized in pharmaceutical, biotechnological and biomedical applications.DiscussionAloe vera extract was processed using a green and facile method. This was a hydrothermal method to reduce silver nitrate to AgNPs@AV. Varying the hydrothermal temperature provided the fine spherical shaped nanoparticles. The size of the nanomaterial was affected by its thermal preparation. The particle size of AgNPs could be tuned by varying both time and temperature. A process using a pure AG phase could go to completion in 6 h at 200 oC, whereas reactions at lower temperatures required longer times. Moreover, the antibacterial effect of this hybrid nanomaterial was sufficient that it could be used to inhibit pathogenic bacteria since silver release was dependent upon its particle size. The high activity of the largest AgNPs might have resulted from a high concentration of aloe vera compounds incorporated into the AgNPs during hydrothermal synthesis.