Combination chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PCA). However, the pharmacokinetic distinction between the relevant drugs is an insurmountable barrier to the realization of their synergistic use against cancer. To overcome the disadvantages of combination chemotherapy in the treatment of PCA, targeted nanoparticles (NPs), which can codeliver docetaxel (DOC) and doxorubicin (DOX) at optimal synergistic proportions, have been designed. In this study, the DOC and DOX codelivery nanoparticles (DDC NPs) were constructed by hyaluronic acid (HA) and cationic amphipathic starch (CSaSt) through a self-assembly process. Human PCA cell lines (PC-3, DU-145, and LNCap) and mouse models were then used for evaluation in vitro and in vivo, respectively, of delivery and antitumor effects. The DDC NPs were spherical with rough surfaces, and the size and zeta potential were 68.4 ± 7.1 nm and -22.8 ± 2.2 mV, respectively. The encapsulation efficiencies of DOC and DOX in the NPs were 96.1 ± 2.3% and 91.4 ± 3.7%, respectively, while the total drug loading was 9.1 ± 1.7%. Moreover, the ratio of DOC to DOX in the DDC NPs was approximately 1:400, which aligned with the optimal synergistic proportions of the drugs. The DDC NPs exhibited excellent loading capacities, performed sustained and enzymatic release, and were stable in PBS, medium, and serum. After investigations in vitro, the DDC NPs were as effective as the dual drug combination in terms of cytotoxicity, antimigration, and apoptosis. Internalization results indicated that the DDC NPs could effectively deliver and fully release the payloads into PCA cells, and the process was mediated by the ligand-receptor interaction of HA with the CD44 protein. Low toxicity in vivo was confirmed by acute toxicity and hemolytic assays. The distribution in vivo showed that DDC NPs could enhance the accumulation of drugs in tumors and decrease nonspecific accumulation in normal organs. More importantly, DDC NPs significantly promoted the curative effect of the DOC and DOX combination in the PCA cell xenograft mouse model, indicating that the drugs with NPs did indeed act synergistically. This study suggests that the DDC NPs possess noteworthy potential as prospects for the development of PCA clinical chemotherapy.

Objectives: The aim of this study was to study the effects of resveratrol on severe acute pancreatitis (SAP)-induced brain injury. Methods: Ninety-six male Sprague-Dawley rats were randomly divided into 4 equal groups: sham operation, SAP, resveratrol-treated (RES), and dexamethasone-treated. Each group was evaluated at 3, 6, and 12 hours. Levels of serum myelin basic protein and zonula occludens 1 (Zo-1) were determined by enzyme-linked immunosorbent assay. The brain and pancreatic tissues were examined using electron microscopy. Expressions of Bax, Bcl-2, and caspase-3 were observed using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Western blotting. Cytochrome c was detected using Western blotting alone. Results: Myelin basic protein and Zo-1 levels of the RES group were lower than the SAP group at all time points (P < 0.05). The RES group had significantly improved pathologic brain, increase in Bcl-2 expression, and decrease in Bax and caspases-3 expressions compared with the SAP group. Conclusions: The degradation of Zo-1 is involved in the pathophysiology of brain injury in SAP; MBP can be used as a marker of brain injury in SAP. The protective effect of resveratrol might be associated with the up-regulation of Bcl-2 and down-regulation of Bax and caspase-3.

Background: Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared.

Objective: To investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines. Methods: In vivo tumour xenograft anticancer assays were undertaken to confirm the anticancer activity of PL. Cell viability, flow cytometry and Western blot assays were undertaken to evaluate the anticancer effects of PL, VC and combinations of PL and VC in AGS and KATO III cells. Results: Both PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect. Conclusions: PL combined with VC exhibited a stronger anticancer effect by regulating the ROS–STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.