No abstract

Among medical imaging modalities available in the clinic, ultrasonography is the most convenient, inexpensive, ionizing-radiation-free, and most common. Micrometer-size perfluorocarbon bubbles have been used as efficient contrast for intravascular ultrasonography, but they are too big for tumor penetration. Nanodroplets (250-1000 nm) encapsulating both perfluorocarbon and drug have been used as an ultrasound-triggered release drug delivery platform against cancer, but they are generally not useful as a tumor imaging agent. The present study aims to develop a type of pH-sensitive, polymersome-based, perfluorocarbon encapsulated ultrasonographic nanoprobe, capable of maintaining at 178 nm during circulation and increasing to 437 nm at the acidic tumor microenvironment. Its small size allowed efficient tumor uptake. At the tumor site, the nanoparticle swells, resulting in lowering of the vaporization threshold for the perfluorocarbon, efficient conversion of nanoprobes to echogenic nano/microbubbles for ultrasonic imaging, and eventual release of doxorubicin from the theranostic nanoprobe for deep tissue chemotherapy, triggered by irradiation with low-frequency ultrasound.

Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy.Methods: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD). PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure. Then, in vitro studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells. PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and in vivo PDT efficacy.Results: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure. The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy.Conclusions: This is the first preclinical investigation of MBs applied in PDT for PCa. PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors. PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa. This strategy carries enormous clinical potential for PCa management.

There has been increasing interest in identifying factors to predict subjective well-being in the emerging field of positive psychology over the past two decades. Dispositional hope, which reflects one’s goal-directed tendencies, including both pathway thinking (planning to meet goals) and agency thinking (goal-directed determination), has emerged as a stable predictor for subjective well-being. However, the neurobiological substrates of dispositional hope and the brain-hope mechanism for predicting subjective well-being remain unclear. Here, we examined these issues in 231 high school graduates within the same grade by estimating cortical gray matter volume (GMV) utilizing a voxel-based morphometry method based on structural magnetic resonance imaging. Whole-brain regression analyses and prediction analyses showed that higher dispositional hope was stably associated with greater GMV in the left supplementary motor area (SMA). Furthermore, mediation analyses revealed that dispositional hope mediated the relation between left SMA volume and subjective well-being. Critically, our results were obtained after adjusting for age, sex, family socioeconomic status and total GMV. Altogether, our study presents novel evidence for the neuroanatomical basis of dispositional hope and suggests an underlying indirect effect of dispositional hope on the link between brain gray matter structure and subjective well-being.