阿霉素纳米粒对MRP介导的膀胱肿瘤多药耐药细胞株EJ/MRP多药耐药性的逆转作用

目的 研究阿霉素纳米粒对多药耐药相关蛋白(MRP)介导的膀胱肿瘤多药耐药的逆转作用.方法 采用四甲基偶氮唑盐(MTT)法测定药物的体外杀伤作用,应用流式细胞术测定细胞内药物浓度.结果 阿霉素纳米粒对EJ细胞的细胞毒作用与阿霉素相似,EJ/MRP 细胞对阿霉素纳米粒较阿霉素敏感4.00倍.结论 阿霉素纳米粒通过增加耐药细胞内阿霉素浓度而有效逆转多药耐药.     

纳米载药系统逆转肿瘤多药耐药的研究进展

目的:介绍纳米载药系统在逆转肿瘤多药耐药(MDR)方面的研究进展。方法:查阅近年来的相关文献,对纳米载体的特点,逆转MDR的机制及其在此领域的应用进行综述。结果:纳米技术可以使药物通过主动或被动靶向作用,更多地被肿瘤细胞摄取而逆转MDR。纳米载药系统还可以作为RNA的载体,通过基因干扰技术逆转肿瘤的MDR。结论:与单一功能和组成的载药系统相比,多功能或药物联用的纳米载药系统在逆转MDR方面更具优势。     

肿瘤多药耐药机制及其逆转方案的研究

肿瘤细胞产生的多药耐药(multidrug resistance,MDR)是临床上肿瘤化学治疗失败的主要原因之一。MDR产生机制非常复杂,对肿瘤多药耐药机制的研究以及寻找高效、低毒、作用靶点广泛的逆转肿瘤耐药的药物,已成为肿瘤治疗亟待解决的关键性问题。本文就肿瘤多药耐药产生的可能途径和逆转策略进行综述,为临床医师针对肿瘤患者制定个体化化疗方案,达到减少耐药性、提高临床疗效的目的提供参考资料。     

阿霉素纳米粒对白血病多药耐药细胞株K562/ADR耐药性的逆转作用

目的:研究阿霉素纳米粒对人白血病多药耐药细胞株K562/ADR耐药性的逆转作用.方法:采用MTT法测定药物的体外杀伤作用,应用流式细胞术测定细胞内药物浓度.结果:阿霉素纳米粒和阿霉素对K562细胞细胞毒作用相似,K562/ADR对阿霉素纳米粒较阿霉素敏感2.63倍,细胞内阿霉素浓度显著增加可能是关键因素.结论:阿霉素纳米粒通过增加耐药细胞内阿霉素浓度有效逆转多药耐药.     

肿瘤多药耐药机制及其逆转剂研究进展

肿瘤细胞多药耐药性（multidrug resistance,MDR）的产生是导致肿瘤化疗失败的主要原因之一。MDR是指肿瘤细胞对一种抗肿瘤药物产生耐药性的同时,对结构和作用机制完全不同的其他抗肿瘤药物产生交叉耐药性的现象。因此,研究MDR产生的机制、寻求有效的耐药逆转剂及逆转措施,克服MDR现象已成为国内外的研究热点。本文就MDR产生的机制、目前国内外逆转耐药的研究进展做一综述。     

阿霉素纳米粒对P-gp介导的膀胱肿瘤多药耐药细胞株BIU-87/ADM多药耐药性的逆转作用

目的:研究阿霉素纳米粒对P-gp介导的膀胱肿瘤多药耐药的逆转作用.方法:采用甲基噻唑基四唑(MTT)法测定药物的体外杀伤作用,应用流式细胞术测定细胞内药物浓度.结果:阿霉素纳米粒和阿霉素对BIU-87的细胞毒作用相似,BIU-87/ADM对阿霉素纳米粒较阿霉素敏感3.50倍,细胞内阿霉素浓度显著增加可能是关键因素.结论:阿霉素纳米粒通过增加耐药细胞内阿霉素浓度有效逆转多药耐药.     

肿瘤细胞多药耐药性的研究进展

肿瘤细胞的耐药性,是肿瘤化疗失败的主要原因之一.近年国内外研究进展迅速.现就收集到的部分肿瘤耐药机理及其有关逆转剂作一简要综述.1 多药耐药性(multidrug resistance,MDR)MDR是指肿瘤细胞先天存在或经化疗药物诱导后表现出的对一种抗肿瘤药物出现耐药的同时,对其他结构不同,作用靶位不同的抗肿瘤药物也具有抗药性,这一现象被称之为多药耐药性.1968年美国kesscl等首次报道小鼠白血病瘤株的交叉耐药性以后,越来越多研究表明:肿瘤细胞的耐药性不但与肿瘤细胞本身的特点有关,也与肿瘤细胞外的环境因素有关.肿瘤细胞耐药可具有1种或1种以上耐药机制,不同的瘤细胞及不同部位的同种肿瘤细胞可具有不同的耐药机理和不同程度的耐药性.MDR形成机理复杂,     

中药抗肿瘤多药耐药机制的研究进展

肿瘤治疗中化疗药物的使用很大程度上抑制了肿瘤的生长,复发及转移,但肿瘤多药耐药现象的出现严重影响了化疗的疗效及肿瘤患者的生存期。多药耐药是肿瘤细胞在接触某种化疗药物之后,对其产生耐药性,同时对其他结构类似的化疗药物也产生交叉抗药性的一种肿瘤治疗进程中出现的难题。越来越多的中药制剂已表现出逆转肿瘤多药耐药的潜力,对其作用机制的研究也越发得到关注。本文将综述一下中药抗肿瘤多药耐药的广泛机制,并以胃癌为例进行较详细阐述,最后提出一些中药抗肿瘤多药耐药的研究新思路。     

新型给药系统在肿瘤多药耐药逆转中的应用

肿瘤的多药耐药(MDR)是肿瘤治疗遇到的主要障碍之一。逆转MDR成为肿瘤治疗面临的重要课题。本文简要介绍了国内外研究者运用纳米粒、胶束、脂质体和微乳作为给药系统,在减少或逆转肿瘤MDR研究领域的进展情况。具有合适粒径的纳米粒和微乳、可控释药的胶束、细胞膜融合性较好的脂质体以及对这些制剂的主动靶向修饰可改变抗肿瘤药物的生物分布,减少或逆转MDR,进而提高抗肿瘤药物的作用。因此,在研究肿瘤MDR逆转时,正确应用给药系统具有重要意义。     

卡莫氟固脂纳米粒对人大肠癌细胞多药耐药的逆转的机制研究

研究卡莫氟固脂纳米粒对人大肠癌细胞多药耐药的逆转作用,并对其逆转机制进行了初步探讨.采用MTT法比较了卡莫氟不同药物形式的细胞毒作用;采用RT-PCR技术考察卡莫氟固脂纳米粒对敏感和耐药人大肠癌细胞中mdr 1和MRP的基因表达的影响.卡莫氟固脂纳米粒能下调耐药人大肠癌细胞中mdr 1的mRNA表达,对其中的MRP的mRNA的表达没有显著影响.卡莫氟固脂纳米粒能逆转人大肠癌细胞由mdr 1 介导的多药耐药,而对MRP介导的多药耐药没有显著影响.     

Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system

Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.     

纳米载药系统逆转肿瘤及骨肉瘤多药耐药的研究进展

多药耐药是肿瘤化疗中的重要难题,多药耐药的机制复杂,目前尚无有效的治疗策略。纳米载药系统具有靶向性、载药种类多样等优点,近年来成为对抗肿瘤多药耐药的递药载体的重要研究方向。对肿瘤抑制的不同机制进行讨论,并对纳米载药系统逆转骨肉瘤多药耐药的研究进展进行综述。     

Nano-based strategies to overcome p-glycoprotein-mediated drug resistance

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.

Areas covered: Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.

Expert opinion: Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.     

Lipid-based drug delivery systems for cancer treatment

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concluded that biodistribution profiles of chemotherapy agents can be controlled by their loading to such nanoplatforms. Lipid-based nanomedicines offer an interesting approach to the delivery of anticancer drugs to brain tumors, and to reverse multi-drug resistance of cancer cells. Finally, a deep evaluation of the applicability of drug delivery strategies in the formulation of lipid-based nanoplatforms is carried out. They involve active drug targeting (including ligand-mediated delivery, and stimuli-sensitive carriers), and passive drug targeting (through the enhanced permeability and retention effect) to tumors.     

Revisiting the role of nanoparticles as modulators of drug resistance and metabolism in cancer

Introduction: Drug resistance is the major obstacle impeding the efficacy of chemotherapeutic agents. Although numerous drug delivery techniques have been developed to combat drug resistance, their limitations of non-specific targeting and inconsistent bioavailability has led to the search of novel delivering strategies, such as nanoparticles.

Areas covered: Nanoparticles for anti-cancer drug delivery are microscopic preparations encapsulating a chemotherapeutic and a chemosensitizer into a rationally designed drug delivery vehicle. Nano-strategies directed against multi-drug resistance (MDR) can be categorized into those inhibiting the drug efflux pumps, those effective against the cellular factors of drug resistance, and the combinational based strategies. Here, we review the most recent literature to reposition nanoparticles as chemotherapeutics and inhibitors of MDR.

Expert Opinion: Novelty in anti-cancer drug delivery has led to the formulation of chemotherapeutics and MDR inhibitors as nano-preparations, which are multi-functional and have better tumor cell-targeting effects. Their characteristics of size and surface attachments make them readily diffusible through the tumor vasculature and increase their retention time as well. With a better understanding of the molecular mechanisms of drug resistance, more potent and multi-targeted nano-preparations can be formulated in the near future.     

Drug targeting to cancer by nanoparticles surface functionalized with special biomolecules

Nanoparticulate-based drug carriers have been developed to overcome the problems of conventional anticancer pharmacotherapy, i.e., the little specificity and low accumulation of the drug into the tumor interstitium, and the extensive biodistribution leading to severe toxicity. Unfortunately, conventional nanoparticles have been demonstrated to merely accumulate the loaded drug into organs associated to the reticuloendothelial system, e.g., the liver. Recently, drug delivery strategies involving the use of nanoplatforms surface decorated with unique biomolecules have demonstrated their potential in concentrating the chemotherapy agent specifically into the malignant cells. This review will be focused on the analysis of the current state of the art and future perspectives of such passive and active targeting strategies based on the enhanced permeability and retention effect and on a ligand-mediated transport, respectively. Special attention will be given to the use of these surface functionalized nanocarriers to overcome multi-drug resistances in cancer cells.     

Overcoming multidrug resistance with nanomedicines

Introduction: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.

Areas covered: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.

Expert opinion: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.     

Cancer-targeted polymeric drugs

A major challenge in cancer chemotherapy is the selective delivery of small molecule anti cancer agents to tumor cells. Water-soluble polymer-drug conjugates exhibit good water solubility, increased half-life, and potent anti tumor effects. By localizing the drug at the desired site of action, macromolecular therapeutics have improved efficacy and enhanced safety at lower doses. Since small molecule drugs and macromolecular drugs enter cells by different pathways, multi-drug resistance (MDR) can be minimized. Anti-cancer polymer-drug conjugates can be divided into two targeting modalities: passive and active. Tumor tissues have anatomic characteristics that differ from normal tissues. Macromolecules penetrate and accumulate preferentially in tumors relative to normal tissues, leading to extended pharmacological effects. This "enhanced permeability and retention" (EPR) effect is the principal reason for current successes with macromolecular anti-cancer drugs. Both natural and synthetic polymers have been used as drug carriers, and several bioconjugates have been clinically approved or are in human clinical trials. While clinically useful anti-tumor activity has been achieved using passive macromolecular drug delivery systems, further selectivity is possible by active targeting. Attachment of targeting moieties to the polymer backbone can further exploit differences between cancer and normal cells through selective receptor-mediated endocytosis. This strategy would augment the EPR effect, thereby further improving the therapeutic index of the macromolecular drug. This review discusses the development and therapeutic potential of prototype macromolecular drugs for use in cancer chemotherapy. Specific examples are selected to illustrate the basic design principles for soluble polymeric drug delivery systems.