A novel conjunction of folate-targeted carbon nanotubes containing protohemin and oridonin-liposome loaded microbubbles for cancer chemo-sonodynamic therapy

Abstract

To facilitate targeting drug delivery and combined therapy, we constructed a novel drug carrier, in which oridonin-liposome containing microbubbles (LUMO) are covalently adhered to folic acid-conjugated multiwalled carbon nanotubes loaded with protohemin (FMTP) to form a novel conjugate (FMTP-LUMO). Oridonin (ORI) is used as a chemotherapeutic drug for chemotherapy (CHT), whereas protohemin (Ph) is applied in the field of sonodynamic therapy (SDT) as a sonosensitizer. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumour effects in HepG-2 cell tumour-bearing mice submitted to chemo-sonodynamic therapy, SDT alone and CHT alone were evaluated upon ultrasound exposure. The results showed that the growth inhibition rates on FMTP-LUMO, FMTP, and LUMO were 95.4?±?5.9%, 63.9?±?7.4%, and 42.3?±?2.9% in vitro, respectively. FMTP-LUMO exhibited strong binding to HepG-2 cells than MTP-LUMO. The chemo-sonodynamic therapy demonstrated a cooperative effect, resulting in significantly higher therapeutic efficacy for liver cancer. After treatment for 10 d, the tumour inhibition ratio for FMTP-LUMO exceeded to 90%, clearly higher than that of FMTP (42.8%) and LUMO (32.5%). Thus, FMTP-LUMO could serve as a highly effective drug carrier for chemo-sonodynamic therapy.     

Preparation of nano cationic liposome as carrier membrane for polyhexamethylene biguanide chloride through various methods utilizing higher antibacterial activities with low cell toxicity

This study suggested successful encapsulation of polyhexamethylene biguanide chloride (PHMB) into nano cationic liposome as a biocompatible antibacterial agent with less cytotoxicity and higher activities. Phosphatidylcholine, cholesterol and stearylamine were used to prepare nano cationic liposome using thin film hydration method along with sonication or homogeniser. Sonication was more effective in PHMB loaded nano cationic liposome preparation with smaller size (34?nm). FTIR, ¹H NMR and XRD analyses were used to confirm the encapsulation of PHMB into nano cationic liposome. PHMB inclusion in nano cationic liposome was beneficial for increased antibacterial activity against Staphylococcus aureus and Escherichia coli. PHMB-loaded cationic liposome enables to deliver high concentrations of the antibacterial agent into the infectious cell. The cytotoxicity of PHMB entrapped in positively charged liposome was prominently reduced showing no significant visible detrimental effect on normal primary human skin fibroblast cell lines morphology confirming the effective role of cationic liposome encapsulation. Comparing with PHMB alone, encapsulation of PHMB in nano cationic liposome resulted in significant increase in cell viability from 2.4 to 63%.     

尼妥珠单抗联合紫杉醇脂质体、顺铂辅治晚期鼻咽癌的疗效观察

目的评价晚期鼻咽癌(NPC)患者应用尼妥珠单抗联合紫杉醇脂质体、顺铂治疗方案的临床疗效及安全性。方法对16例晚期NPC患者采用尼妥珠单抗联合紫杉醇脂质体、顺铂方案治疗:尼妥珠单抗200mg,每周1次,连用6个周期,之后同剂量每2周1次进行巩固治疗,至病情进展停用;紫杉醇脂质体175mg/m2静脉滴注;顺铂(DDP)75mg/m2静脉滴注,分3d用,21d为1个周期。治疗后观察其疗效及不良反应。结果 16例患者中完全缓解3例(18.75%),部分缓解12例(75.00%),疾病稳定1例(6.25%),进展0例,总有效率(RR)为93.75%。1年总生存率(OS)为93.75%,1年无瘤生存率(DFS)为87.50%。主要不良反应为骨髓抑制、胃肠道反应和关节肌肉疼痛,Ⅲ～Ⅳ度白细胞减少发生率为18.75%,无严重并发症发生。结论尼妥珠单抗联合紫杉醇脂质体、顺铂辅治晚期NPC有较好的疗效,且不良反应少,值得推广应用。     

Update on non-viral delivery methods for cancer therapy: possibilities of a drug delivery system with anticancer activities beyond delivery as a new therapeutic tool

Importance of the field: Cancer is the most formidable human disease. Owing to the heterogeneity of cancer, a single-treatment modality is insufficient for the complete elimination of cancer cells. Therapeutic strategies from various aspects are needed for cancer therapy. These therapeutic agents should be carefully selected to enhance multiple therapeutic pathways. Non-viral delivery methods have been utilized to enhance the tumor-selective delivery of therapeutic molecules, including proteins, synthetic oligonucleotides, small compounds and genes.

Areas covered in this review: As non-viral delivery methods, liposomes and polymer-based delivery materials to target tumors mainly by systemic delivery, physical methods including electroporation, sonoporation, and so on, to locally inject therapeutic molecules, and virosomes to use the viral infectious machinery for the delivery of therapeutic molecules are summarized.

What the reader will gain: This article aims to provide an overview of the characteristic properties of each non-viral vector. It will be beneficial to utilize appropriately the vector for cancer treatment.

Take home message: Efficient and minimally invasive vectors are generally considered to be the ideal drug delivery system (DDS). However, against cancer, DDS equipped with antitumor activities may be a therapeutic choice. By combining therapeutic molecules with DDS having antitumor activities, enhancement of the multiple therapeutic pathways may be achieved.     

长托宁对有机磷中毒伴中枢神经系统损害的疗效观察

目的分析长托宁在急性有机磷农药中毒伴中枢神经系统损害中的应用疗效。方法选择应用长托宁治疗的重度急性有机磷农药中毒伴中枢神经系统损害患者48例作为治疗组,并将过去使用阿托品治疗的重度有机磷农药中毒伴神经系统损害的43例既往病例作为对照组进行对比,比较两组的中毒症状持续时间、不良反应、胆碱酶活力恢复情况及治愈率。结果治疗组较对照组M样症状及中枢神经症状消失时间明显缩短,平均用药次数及用药量明显减少,并发症发生率与病死率明显降低。结论长托宁治疗重度有机磷农药中毒伴中枢神经系统损害较阿托品疗效好,不良反应发生率低。     

The olfactory tubercle as a site of action of neuroleptics with an atypical profile in the paw test: effect of risperidone,prothipendyl, ORG 5222, sertindole and olanzapine

The paw test was used to detect the preclinical profile (classical versus atypical) of five putative, atypical neuroleptics, namely olanzapine, sertindole, risperidone, prothipendyl and ORG 5222. In the paw test classical neuroleptics increase the hindlimb reaction time (HRT), a parameter with predictive validity for antipsychotic efficacy, at doses comparable to those necessary for increasing forelimb reaction time (FRT), a parameter with predictive validity for extrapyramidal side-effects, whereas atypical neuroleptics increase HRT at doses that are much smaller than those increasing FRT. All tested compounds showed the profile of atypical neuroleptics in the paw test. Using the FRT/HRT ratio of minimum effective doses as overall predictor of a favourable ratio of extrapyramidal and therapeutic effects of these drugs, the following order was found: olanzapine (20) > sertindole = risperidone = prothipendyl (10) > ORG 5222 (3). The ability of compounds to attenuate locomotor activity elicited either from the olfactory tubercle (10 µg dopamine: OT test) or from the nucleus accumbens (1 µg ergometrine: ACC test) was used to establish whether the compounds preferentially act in one of these structures. Previous research has shown that classical neuroleptics are far less potent in the OT test than in the ACC test, whereas atypical neuroleptics are far more potent in the OT test than in the ACC test. All five agents preferentially acted in the olfactory tubercle. The order of potency in the olfactory tubercle was as follows: sertindole > ORG 5222 > risperidone > olanzapine > prothipendyl. It is concluded that risperidone, prothipendyl, ORG 5222, sertindole and olanzapine not only show the profile of atypical neuroleptics in the paw test, but also preferentially act in the olfactory tubercle, but not in the nucleus accumbens, viz. two features that they share with the atypical neuroleptics clozapine and thioridazine and with the putative, atypical neuroleptics raclopride and remoxipride.