ABSTRACT
Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.
ABSTRACT
Objective:To investigate the ultrasonographic characteristics and risk factors of breast cancer internal mammary lymph node (IMLN) metastasis.Methods:A retrospective analysis of 296 first diagnosed breast cancer patients in the Fourth Hospital of Hebei Medical University from March 2010 to May 2020. IMLN was divided into metastatic group (236 cases) and non-metastatic group (60 cases) based on pathology. Chi-square test and independent sample t test were used to analyze the ultrasound characteristics of IMLN metastasis and factors related to metastasis. ROC curve analysis of IMLNs were plotted to obtain the diagnostic thresholds and their sensitivity and specificity.Univariate and multivariate Logistic analysis was used to analyze the risk factors of IMLN metastasis. Results:①The appearances of IMLN in ultrasound were normal type, thickened-cortex type, unclear hilus structure type and thickened-nodular soft tissue type. ②In the two groups, the differences in IMLN long diameter, thickness diameter, number, and lymphatic hilum structure type were statistically significant (all P<0.05), and there were no significant differences in IMLN long diameter/thickness diameter and IMLN blood supply (all P>0.05). ③The long diameter threshold of IMLN for diagnosis of metastasis was 10.5 mm, the are under the ROC curve(AUC) was 0.825, with sensitivity of 58.5% and specificity 93.3%; thickness and diameter threshold was 4.5 mm, AUC was 0.790, with sensitivity 66.9% and specificity 75.0%. The sensitivity and specificity of the diagnosis of long-diameter combined structure type were 56.3% and 93.3%, respectively; the sensitivity and specificity of the diagnosis of thick-diameter combined structure type were 64.8% and 81.7%, respectively. The cortical thickness threshold was 1.9 mm, and the diagnostic sensitivity and specificity were 91.9% and 86.7%, respectively. ④The risk factors of IMLN metastasis inculded univariate analysis showed tumor length, tumor volume, axillary lymph node long diameter, axillary lymph node metastasis, and clavicle lymph node metastasis. There was a statistically significant difference in the pathology of the lower lymph nodes between the two groups ( P<0.05). Multivariate analysis showed that the long diameter of the tumor and the metastasis of the axillary lymph nodes were independent risk factors of IMLN metastasis. Conclusions:The metastatic IMLN mostly manifest as no lymphatic hilum structure or cortical thickening (≥1.9 mm), and multiple IMLN can help diagnose metastasis.Ultrasound can better assess breast cancer IMLN metastasis, and the diagnostic efficiency of IMLN long-diameter combines structure type is higher.Independent risk factors for IMLN metastasis include tumor size and axillary lymph node metastasis.