Small-molecule inhibitors have revolutionized treatment of certain genomically defined solid cancers. Despite breakthroughs in treating systemic disease, central nervous system (CNS) metastatic progression is common, and advancements in treating CNS malignancies remain sparse. By improving drug penetration across a variably permeable blood-brain barrier and diffusion across intratumoral compartments, more uniform delivery and distribution can be achieved to enhance efficacy.Experimental Design: Ultrasmall fluorescent core-shell silica nanoparticles, Cornell prime dots (C' dots), were functionalized with a v integrin-binding (cRGD), or nontargeting (cRAD) peptides, and PET labels ( 124 I, 89 Zr) to investigate the utility of dualmodality cRGD-C' dots for enhancing accumulation, distribution, and retention (ADR) in a genetically engineered mouse model of glioblastoma (mGBM). mGBMs were systemically treated with 124 I-cRGD-or 124 I-cRAD-C' dots and sacrificed at 3 and 96 hours, with concurrent intravital injections of FITC-dextran for mapping blood-brain barrier breakdown and the nuclear stain Hoechst. We further assessed target inhibition and ADR following attachment of dasatinib, creating nanoparticledrug conjugates (Das-NDCs). Imaging findings were confirmed with ex vivo autoradiography, fluorescence microscopy, and p-S6RP IHC.Results: Improvements in brain tumor delivery and penetration, as well as enhancement in the ADR, were observed following administration of integrin-targeted C' dots, as compared with a nontargeted control. Furthermore, attachment of the smallmolecule inhibitor, dasatinib, led to its successful drug delivery throughout mGBM, demonstrated by downstream pathway inhibition.Conclusions: These results demonstrate that highly engineered C' dots are promising drug delivery vehicles capable of navigating the complex physiologic barriers observed in a clinically relevant brain tumor model.

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

This study explored behavioral models based on low-cost carrier customers’ use of a ticketing app. Technology readiness, service convenience, and corporate credibility were evaluated in the model. A total of 815 valid responses were collected from customers of Tigerair, Taiwan, who had flown from one of the two major international airports in Taiwan. With technology readiness regarded as the grouping variable, the results indicated that corporate credibility significantly affected customers’ intentions to use the app, whereas the effects of service convenience on the technology exploration, technology contradiction, and the technology insecurity groups varied. Finally, this paper presents a discussion of management implications and suggestions for future studies.

Antibody−drug conjugates (ADCs) have recently demonstrated impressive successes in targeted drug delivery. Ultrasmall (<10 nm) nanoparticle−drug conjugates (NDCs) share many similarities with ADCs, while their unique physicochemical properties can be further molecularly engineered to overcome the limitations of ADCs presented by tumor heterogeneity. Key challenges in NDC development include linkage chemistry design between nanoparticle carriers and cytotoxic drugs, as well as meeting the stringent criteria for manufacturing controls, stability, and drug release to enable successful clinical translation. Here, we report a robust chemical approach to covalently link both chemotherapeutic drugs and targeting moieties to a poly(ethylene glycol) (PEG)-coated (PEGylated) ultrasmall silica nanoparticle platform via precisely tailoring the particle surface chemistry. This approach employs the interstitial space between PEG chains on the particle surface to load drugs, enabling the significantly enhanced drug loading capacity as compared to ADCs while the favorable biodistribution and pharmacokinetics profiles are maintained. To achieve both high plasma stability and effective drug release in cancer, cyclopentadiene silane molecules are first inserted into the PEG layer of the particles and condensed with silanol groups on the silica core surface. Via the Diels−Alder reaction, the cyclopentadiene groups are then functionalized with groups enabling click chemistry, and cytotoxic payloads are finally clicked onto the particles via cleavable linkers for drug release within the cancer tissue. The targeted NDC resulting from the systematic screening strategy described here has recently advanced to a phase 1/2 human clinical trial.

Purpose This study aimed to translate the English version of the Action Research Arm Test (ARAT) into Chinese and to evaluate the initial validation of the Chinese version (C-ARAT) in patients with a first stroke. Methods An expert group translated the original ARAT from English into Chinese using a forward-backward procedure. Forty-four patients (36 men and 8 women) aged 22–80 years with a first stroke were enrolled in this study. The participants were evaluated using 3 stroke-specific outcome measures: C-ARAT, the upper extremity section of the Fugl–Meyer assessment (UE-FMA), and the Wolf Motor Function Test (WMFT). Internal consistency was analysed using Cronbach's α coefficients and item-scale correlations. Concurrent validity was determined using Spearman's rank correlation coefficients. Floor and ceiling effects were considered to be present when more than 20% of patients fell outside the preliminarily set lower or upper boundary, respectively. Results The C-ARAT items yielded excellent internal consistency, with a Cronbach's α of 0.98 (p < 0.001) and item-total correlations ranging from 0.727 to 0.948 (p < 0.001). The C-ARAT exhibited good-to-excellent correlations with the UE-FMA and WMFT functional ability (WMFT-FA) scores, with respective ρ values of 0.824 and 0.852 (p < 0.001), and an excellent negative correlation with the WMFT performance time (WMFT-time), with a ρ value of -0.940 (p < 0.001). The C-ARAT subscales generally exhibited good-to-excellent correlations with stroke-specific assessments, with ρ values ranging from 0.773 to 0.927 (p < 0.001). However, the gross subscale exhibited moderate-to-good correlations with the UE-FMA and WMFT-FA scores, with respective ρ values of 0.665 and 0.720 (p < 0.001). No significant floor effect was observed, and a significant ceiling effect was observed only on the WMFT-time. Conclusions The C-ARAT demonstrated excellent internal consistency and good-to-excellent concurrent validity. This test could be used to evaluate upper extremity function in stroke patients without cognitive impairment.