The binding site barrier (BSB) was originally proposed to describe the binding behavior of antibodies to cells peripheral to blood vessels, preventing their further penetration into the tumors. Yet, it is revisited herein to describe the intratumoral cellular disposition of nanoparticles (NPs). Specifically, the BSB limits NP diffusion and results in unintended internalization of NPs by stroma cells localized near blood vessels. This not only limits the therapeutic outcome but also promotes adverse off-target effects. In the current study, it was shown that tumor-associated fibroblast cells (TAFs) are the major component of the BSB, particularly in tumors with a stroma-vessel architecture where the location of TAFs aligns with blood vessels. Specifically, TAF distance to blood vessels, expression of receptor proteins, and binding affinity affect the intensity of the BSB. The physical barrier elicited by extracellular matrix also prolongs the retention of NPs in the stroma, potentially contributing to the BSB. The influence of particle size on the BSB was also investigated. The strongest BSB effect was found with small (∼18 nm) NPs targeted with the anisamide ligand. The uptake of these NPs by TAFs was about 7-fold higher than that of the other cells 16 h post-intravenous injection. This was because TAFs also expressed the sigma receptor under the influence of TGF-β secreted by the tumor cells. Overall, the current study underscores the importance of BSBs in the delivery of nanotherapeutics and provides a rationale for exploiting BSBs to target TAFs.
Here, a novel multifunctional phosphor of Li1−xGa5O8:xPr3+ is reported. The crystal structure, mechanoluminescence (ML), persistent luminescence (PersL), photoluminescence (PL) and photoluminescence excitation (PLE) are systematically studied. LiGa5O8 emits blue PersL peaked at 437 nm after irradiation by a 254 nm lamp for 10 s, and corresponding PersL can be observed for 30 min by naked eyes. In the same case, the PersL from Li0.995Ga5O8:0.005Pr3+ covers visible to near‐infrared lights (400–1000 nm) which can persist for 120 min. Thermoluminescence analysis shows Pr3+ doping not only increases the shallower trap (0.73 eV) concentration by at least 20 times but also helps the formation of deeper trap centers (0.87 eV). The differences between ML and PersL spectra reveal the selective effects of mechanical stimuli on the transitions of Pr3+ ions. In the end, the fabrication of an intelligent PersL quick response code (QR‐code) permits optical information write‐in after irradiation by a 254 nm lamp and then cryptical information of “SCUT” can be read out by thermal stimulation which shows the potential in information storage. Moreover, the biological tissues penetration experiments and cytotoxicity tests are carried out to display the potential of PersL in bioimaging.
Micro-and nano-machining technology has been applied in industry to generate high-precision parts with micro/nanometric accuracy or feature size in the recent decades. Cutting is one of the most powerful manufacturing processes, and the material removal mechanism is urgently demanded by the industry to understand and improve the micro/nano-machining process efficiently at a low cost. This paper presents the recent advances in cutting mechanism and its applicability for predicting the surface generation and chip formation, especially when material is removed in micro-and nanoscale. In addition to the industry-concerned performance parameters, fundamental physical parameters such as stresses, strains, temperatures, phase transformation, minimum uncut chip thickness and size effects are discussed in this paper for the indepth understanding of the micro/nano-cutting process.
ObjectiveThe outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic.Methods542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed.Results488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (β=-0.117, p=0.001), emotional function (β=-0.19, p<0.001), social function (β=-0.111, p=0.006), anxiety (β=0.434, p<0.001) and RT interruption (β=0.071, p=0.035) were independent predictors.ConclusionsRT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.
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