Self-targeting platinum(IV) amphiphilic prodrug nano-assembly as radiosensitizer for synergistic and safe chemoradiotherapy of hepatocellular carcinoma.

Chemoradiotherapy is a widely used treatment for patients with malignancies such as hepatocellular carcinoma (HCC). However, it remains challenging to realize safe and synergistic chemotherapy and radiation sensitization. Herein, we design a self-targeting nano-assembly (STNA) based on platinum(IV)-lactose amphiphilic prodrug for synergistic and safe chemoradiotherapy of HCC. The Pt STNA would improve the tumor accumulation due to the targeting ability of lactose to HCC cells. After receptor-mediated endocytosis, Pt STNA would release cisplatin(II) in cancer cells to form DNA-binding, thus inducing DNA damage and cell apoptosis. Meanwhile, the DNA-binding also causes cell cycle arrest in the radiation-sensitive G2/M phase by the up-regulation of phosphorylated checkpoint kinase 1 (p-Chk1) expression. Furthermore, under X-ray irradiation, Pt STNA as radiosensitizer possesses a strong X-ray attenuation ability to deposit more energy, thus elevating the level of reactive oxygen species (ROS) to amplify the cell-killing effect of radiotherapy in the G2/M phase with increased DNA damage. As a result, Pt STNA exhibits significant synergistic therapeutic effects in chemoradiotherapy with no adverse effects in vitro and in vivo. Overall, we present a novel self-targeting nano-assembly strategy based on widely used Pt drugs for synergistic chemotherapy and radiation sensitization of HCC treatment.

Effects of social participation patterns and living arrangement on mental health of Chinese older adults: A latent class analysis.

Objectives: The purpose of this study was to discover patterns of social participation among Chinese older individuals, investigate the links between these patterns and their living arrangements and mental health, and connect these patterns to their background characteristics. Methods: Data were drawn from the 2014 and 2018 waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2537 Chinese elders aged 60 years and over at the baseline. Latent class analysis was used to determine the patterns of social participation. Multinomial logistic regression was used to explore the relationship between patterns of social participation and the sociodemographic and health characteristics of older adults. Binary logistic regression was used to explore the differences and associations between these categories and living arrangement on mental health status, represented by positive and negative emotions. Results: Three patterns of social participation were identified: Low activity (17.5%, n = 443); Moderate activity (36.2%, n = 1,176); and High activity (46.3%, n = 918). At baseline, these patterns were significantly associated with mental health status. Positive and negative emotions were much better in the High activity group than in the other two groups (OR = 1.36, 95% CI = 1.05-1.76 and OR = 1.50, 95% CI = 1.16-1.93). Living arrangement only significantly affected negative emotions (OR=1.25, 95% CI = 1.02-1.53). Age, gender, education, marital status, self-rated health, and activities of daily living limitations all affected social participation patterns. Conclusions: The patterns of social participation and living arrangement of Chinese older adults are significantly associated with mental health. Population-tailored interventions may help liberate older adults from domestic labor and improve social participation. Moreover, family support can decrease negative emotions' damage in old age thus promoting health.

Multifunctional high-Z nanoradiosensitizers for multimodal synergistic cancer therapy.

Radiotherapy (RT) is one of the most common and effective clinical therapies for malignant tumors. However, there are several limitations that undermine the clinical efficacy of cancer RT, including the low X-ray attenuation coefficient of organs, serious damage to normal tissues, and radioresistance in hypoxic tumors. With the rapid development of nanotechnology and nanomedicine, high-Z nanoradiosensitizers provide novel opportunities to overcome radioresistance and improve the efficacy of RT by deposition of radiation energy through photoelectric effects. To date, several types of nanoradiosensitizers have entered clinical trials. Nevertheless, the limitation of the single treatment mode and the unclear mechanism of nanoparticle radiosensitization have hindered the further development of nanoradiosensitizers. In this review, we systematically describe the interaction mechanisms between X-rays and nanomaterials and summarize recent advances in multifunctional high-Z nanomaterials for radiotherapeutic-based multimodal synergistic cancer therapy. Finally, the challenges and prospects are discussed to stimulate the development of nanomedicine-based cancer RT.