Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

The value of subsolid pulmonary nodules in imaging diagnosis of stage ⅠA lung cancer / 中国癌症杂志

Background and purpose: With characteristic but non-specific features, subsolid pulmonary nodules (SSPN) is closely associated with early lung cancer. This study aimed to estimate the imaging value of SSPN in stageⅠA lung cancer, and summarized the radiological features of various SSPNs, retrospectively. Methods:The clinical data and imaging data of 405 patients with solitary pulmonary nodules (SPNs) from Apr. 2008 to Apr. 2014 at Fudan University Shanghai Cancer Center were collected. According to ground-glass opacity (GGO) proportion, SPNs were divided into 3 groups:pure ground-glass opacity (pGGO), mixed ground-glass opacity (mGGO) and solid nodule (SN). The malignant ratios were calculated based on the postoperatively pathological results. Besides, SSPNs were classiifed into stageⅠA lung cancer group and benign lesions group aiming at identifying the differentiating computed tomography (CT) features. Results:Of the enrolled 405 SPN patients, there were 367 SSPNs (including 124 pGGOs and 243 mGGOs) whose incidence in stageⅠA lung cancer group was signiifcantly higher than those in benign group [95.9%(257/268) vs 80.3%(110/137), P<0.001]. The total malignant ratio of SSPN was 70.0%(257/367), mGGO had a higher malignant ratio (72.0%) than those of pGGO (66.1%) and SN (28.9%). The malignant SSPNs were frequently detected in upper lobe of middle-aged women with a higher incidence of irregular edge, spiculation, lobulation and pleural retraction than benign group (P<0.05). Conclusion:SSPN is one of the signiifcantly malignant indicators, and mGGO has the highest malignant tendency. Senility, female, irregular edge, spiculation, lobulation, pleural retraction and pulmonary upper lobe distribution are demonstrated the signiifcant discriminators from benign lesions.

The progress of arterial spin labeling / 中国癌症杂志

As a kind of non-invasive functional magnetic resonance imaging (fMRI) techniques, arterial spin labeling (ASL) takes full advantage of arterial blood as an endogenous tracer to track changes of blood lfow caused by lesions and to obtain the physiological and pathological information of relative tissues avoiding patients’ discomfort and potential danger. This review focused on working principle and categories of ASL, the comparisons with other methods, clinical application, and future prospects of ASL.

The progress of biodegradable biliary stents / 中华肝胆外科杂志

Biodegradable stents have achieved encouraging outcomes in the treatment of benign bile duct stenosis with good biocompatibility,unique biodegradation,and adept physical and mechanical performance.They have a higher biocompatibility than plastic and metal stents and do not require a second surgery for removal.This prevents adverse reactions like restenosis and the tendency to punch and bleed.These biodegradable stents provide a new method of treatment for biliary tract disease,and this review will focus on the animal experiments,clinical application,and future prospects of these stents.