Poor permeation of therapeutic agents and multidrug resistance (MDR) in solid tumors are the two major challenges that lead to the failure of the current chemotherapy methods. Herein, a zero‐waste doxorubicin‐loaded heparin/folic acid/l‐arginine (HFLA‐DOX) nanomotor with motion ability and sustained release of nitric oxide (NO) to achieve deep drug penetration and effective reversal of MDR in cancer chemotherapy is designed. The targeted recognition, penetration of blood vessels, intercellular penetration, special intracellular distribution (escaping from lysosomes and accumulating in Golgi and nucleus), 3D multicellular tumor spheroids (3D MTSs) penetration, degradation of tumor extracellular matrix (ECM), and reversal of MDR based on the synergistic effects of the motion ability and sustained NO release performance of the NO‐driven nanomotors are investigated in detail. Correspondingly, a new chemotherapy mode called recognition‐penetration‐reversal‐elimination is proposed, whose effectiveness is verified by in vitro cellular experiments and in vivo animal tumor model, which can not only provide effective solutions to these challenges encountered in cancer chemotherapy, but also apply to other therapy methods for the special deep‐tissue penetration ability of a therapeutic agent.

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Severe acute pancreatitis (SAP) is the sudden onset of pancreatic inflammation, which is characterized by edema, acinar cell necrosis, hemorrhage and severe inflammation of the pancreas and is associated with a high mortality rate. Daphnetin has been shown to alleviate organ injury in a variety of preclinical animal models of coagulation disorders. The aim of the present study was to investigate the protective effects of daphnetin on severe acute pancreatitis in a rat model. Severe acute pancreatitis in the rat model was induced by retrograde infusion of 5% sodium taurocholate (1 ml/kg) into the bile-pancreatic duct. Daphnetin (4 mg/kg) was administered intraperitoneally at 30 min prior to the infusion of sodium taurocholate. The severity of pancreatitis was evaluated by various analyses of serum amylase and lipase, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels, myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, as well as by histological grading. The levels of TNF-α and IL-1β in the serum were measured by ELISA. The results revealed that the daphnetin-treated SAP rat group (SAP-D) exhibited a lower pathological score of the pancreas compared with the SAP group (SAP). Further analyses demonstrated that the SAP-D group had lower levels of serum amylase, lipase and pro-inflammatory cytokines, including TNF-α and IL-1β, and a decreased MPO activity and MDA content 3, 6 and 12 h subsequent to the infusion of sodium taurocholate compared with the SAP group (SAP). These findings indicated that daphnetin exerted a protective function in the SAP rat model. Therefore, daphnetin may be considered as a potential compound for the therapy and prevention of acute pancreatitis.

In vivo prolonged circulation time and enhanced tumor resistant ability of targeted PTX-loaded FA–Pluronic–PLA nanoparticles.

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