ABSTRACT
Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
ABSTRACT
Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.
ABSTRACT
Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.
ABSTRACT
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
ABSTRACT
This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.
Subject(s)
Mice , Animals , Endothelial Cells , Abietanes , Cell LineABSTRACT
Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.
ABSTRACT
Traditional surgical resection, radiotherapy, and chemotherapy still play a dominant role in the treatment of liver cancer; however, their application in liver cancer patients is often limited by the toxic and side effects, unstable efficacy, and unclear targets of chemotherapeutic drugs. Therefore, in order to improve the efficacy of drugs in the treatment of liver cancer, nanomedicine, which has been developed in the biomedical field in recent years, has attracted more and more attention. Nano-drug delivery system has been gradually applied in clinical research for its advantages of low toxicity, wide bioavailability, controllable drug release, and good stability. This article focuses on the latest research advances in nano-drug delivery system in the treatment of liver cancer.
ABSTRACT
Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
ABSTRACT
Objective:To evaluate the radiosensitivity enhancement effect of FePd@CNTs nanocomposites on human breast cancer MCF-7 cells.Methods:FePd@CNTs nanocomposites were synthesized by chemical reduction method. Transmission electron microscope and energy dispersive spectrometer were utilized to characterize the surface morphology and chemical composition of FePd@CNTs nanocomposites. The compatibility of FePd@CNTs nanocomposites with human normal breast epithelial MCF-10A cells was determined by CCK-8 assay. The radiosensitivity enhancement effect of FePd@CNTs nanocomposites on MCF-7 cells was assessed by CCK-8 assay, flow cytometry and clony formation assay.Results:FePd nanospheres were successfully modified on the surface of CNTs by chemical reduction method. FePd@CNTs nanocomposites showed a low toxicity to MCF-10A cells (IC 50=738.3 μg/m), and effectively enhanced the effect of X-ray radiation on MCF-7 cells (sensibilization ratio=1.22). Conclusion:FePd@CNTs nanocomposites exhibit a promising potential for treating breast cancer and enhancing radiosensitivity effect.
ABSTRACT
Objective:To investigate the antitumor effect of shikonin loaded milk derived exosomes on hepatoma cells.Methods:The experimental study was conducted. Exosomes were isolated from milk by differential centrifugation and be loaded by shikonin to constructed a nano drug loading system. The shikonin content of this nano drug loading system was determined and calculated by spectrophotometry. The cytotoxicity of shikonin loaded milk derived exosomes was evaluated by sulfonyl rhodamine B colorimetry and cell apoptosis was determined by annexin V-FITC/propidium iodide assay. Western blotting was used to detect the Bax and Bcl-2 protein expression level in hepatoma cells. Human HepG2 hepatoma cells treated with shikonin were set as the shikonin treated group and human HepG2 hepatoma cells treated with shikonin loaded milk derived exosomes were set as the shikonin loaded milk derived exosomes treated group. Observa-tion indictors: (1) the loading percentage of shikonin in shikonin loaded milk derived exosomes; (2) the cytotoxicity of shikonin loaded milk derived exosomes on human HepG2 hepatoma cells; (3) cell apoptosis of human HepG2 hepatoma cells; (4) Bax and Bcl-2 protein expression level in human HepG2 hepatoma cells. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups were analyzed using the t test. Results:(1) The loading percentage of shikonin in shikonin loaded milk derived exosomes: the loading percentage of shikonin in shikonin loaded milk derived exosomes was 22.8%. (2) The cytotoxicity of shikonin loaded milk derived exosomes on human HepG2 hepatoma cells: the survival rates of hepatoma cells were 53.9%±2.9% and 45.4%±1.9% in the shikonin treated group and the shikonin loaded milk derived exosomes treated group, respectively, showing a significant difference ( t=46.27, P<0.05). (3) Cell apoptosis of human HepG2 hepatoma cells: the early apoptosis rates of hepatoma cells were 11.3%±1.5% and 14.8%±2.2% in the shikonin treated group and the shikonin loaded milk derived exosomes treated group, respectively, showing no significant difference ( t=1.37, P>0.05). The late and overall apoptosis rates of hepatoma cells were 32.3%±1.3% and 43.6%±4.3% in the shikonin treated group, versus 38.7%±3.2% and 53.5%±4.4% in the shikonin loaded milk derived exosomes treated group, showing significant differences ( t=37.39, 30.97, P<0.05). (4) Bax and Bcl-2 protein expression level in human HepG2 hepatoma cells: Bax and Bcl-2 protein expre-ssion level were 232.0±2.6 and 32.0±1.6 in the shikonin treated group, versus 286.0±3.8 and 17.0±1.5 in the shikonin loaded milk derived exosomes treated group, showing significant differences ( t=69.83, 53.32, P<0.05). Conclusion:The shikonin loaded milk derived exosomes have cytotoxic and apoptosis inducing effects on human HepG2 hepatoma cells, which can inhibit the growth of hepatoma cells.
ABSTRACT
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates
ABSTRACT
Objective: Using polydopamine (PDA) as a carrier to construct a Salviae Miltiorrhizae Radix et Rhizoma (SMRR) nano-delivery system (PDA-SMRR), which can load a large number of SMRR water-soluble components and better exert antioxidation and antistress effect. Methods: PDA-SMRR nanoparticles (PDA-SMRR) were prepared, and the prescription process was investigated and optimized by single-factor experiments. The particle size, potential, and morphology of the nanoparticles were examined by a laser particle size analyzer and a transmission electron microscope. The drug loading and cumulative release rate were analyzed by dialysis. The cardiomyocytes of neonatal rats were extracted and cultured. The CCK-8 experiment was used to investigate the biological safety of PDA-SMRR and verify the protective effect of PDA-SMRR on oxidative stress-induced cardiomyocytes. Results: The optimal drug loading process was pH value 3.5, drug loading time was 12 h, drug loading temperature was room temperature, and PDA-SMRR was successfully prepared. The morphology and size of the nanoparticles were regular and uniform. The particle size and Zeta potential were (459.2 ± 4.5) nm, (3.01 ± 0.3) mV; In vitro release experiments indicated that SMRR was released slowly by the delivery system. CCK-8 experiments showed that PDA-SMRR had good biological safety and nanoparticles can reduce damaged cardiomyocytes caused by oxidative stress. Conclusion: PDA-SMRR can be used as a multi-component medicine depot for SMRR, with high drug loading and sustained release effect, which can effectively reduce the damage of oxidative damage on myocardial cells.
ABSTRACT
The epithelial-to-mesenchymal transition (EMT), a process during which cells undergo transition from a polarized epithelial phenotype to a non-polarized mesenchymal phenotype, executed by transcription factors of Twist, Snail and Zeb families. EMT plays an important role in multiple stages of cancer progression such as initiation, tumor growth, and metastasis. Some active ingredients from Chinese materia medica can inhibit EMT by regulating transcription factors and signaling pathways by multiple targets. However, their therapeutic effect was hindered due to various limitation such as solubility, stability, tissue specificity and safety. Therefore, in order to improve the druggability of active ingredients from Chinese materia medica, enhance the therapeutic effect in inhibiting tumor metastasis mediated by EMT and reduce the toxic and side effects, a variety of nano-drug delivery systems have been developed in recent years. Here, we made a review about these drug delivery systems modulating EMT and their research progress in inhibiting tumor metastasis.
ABSTRACT
Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
ABSTRACT
Immune escape is an important mechanism for the development of tumors. Re-activating the anti-tumor immune response is a key measure for the treatment of malignant tumors. Ginsenoside Rg3 (G-Rg3) is a sterol compound isolated from Panax ginseng. It can improve the anti-tumor immune response of human by up-regulating the autoantigenicity and immunogenicity of tumor cells, enhancing the function of immune effector cells and immune active molecules, and regulating the local immune microenvironment. However, the clinical application of G-Rg3 is limited due to its poor water solubility and low bioavailability. Improved drug delivery systems are the key to solving this problem. Therefore, this paper summarizes the research progress of G-Rg3 on tumor immunoregulation and its nano-drug delivery systems, in order to provide reference for the in-depth study and clinical application of G-Rg3.
ABSTRACT
@#Anti-angiogenic therapy has a wide range of applications in the treatment of tumor. Nano drug delivery system can contribute to higher efficacy and lower toxicity in anti-angiogenic therapy. This article reviews the application of nano drug delivery system in anti-angiogenic therapy and introduces the strategies to improve its treatment efficiency with varieties of nanoparticles, providing reference for the development of anti-angiogenic therapy.
ABSTRACT
Cancer is one of the major diseases that seriously endanger human health. Recurrence and metastasis may still oc-cur after traditional treatment. The basic reason is the presence of cancer stem cells(CSCs)in tumor tissues. CSCs have a high degree of proliferative ability,self-renewal,multi-directional differentiation,highly tumorigenicity and multi-drug resistance,which control the occurrence and development of tumors,chemotherapy tolerance,recurrence and metastasis. Therefore,clearing CSCs is one of effec-tive ways to improve the curative rate of cancer. Nano-carriers have many advantages such as small size,large specific surface area, good biocompatibility and degradation in vivo. They are often used for targeted delivery and sustained release of drugs,which overcome the toxic side effects of traditional chemotherapeutic drugs,avoid surgical damage and kill CSCs. This paper will review the characteris-tics of CSCs and nano drug-loading systems as well as their research progress of nano drug-loading systems in CSCs in recent years.
ABSTRACT
Malignant tumors are the second most important cause of death after cardiovascular and cerebrovascular diseases. Chemotherapeutic drugs for tumor treatment have strong toxic side effects. The common solution is to use nanoparticle as a carrier that can deliver drugs to tumor issues so as to kill the tumor cells. However, most of the current drug-carriers have a serious drug loss before reaching the tumor area, which makes the difficult control of drug release. Multi-stimulus responsive nano-carrier systems can overcome these drawbacks and make drug release controllable. pH/redox dual sensitive nano-carrier systems are currently hot research direction. In this paper, the research progress of pH/redox dual sensitive nano-carrier systems in recent years was reviewed in order to provide reference for relative researches.
ABSTRACT
@#Tumor occurrence is usually recognized as the interplay between genetic variations within the tumor and the environment. During a long time, great effort has been made in killing cancer cells. However, the role of tumor microenvironment has been largely ignored, which plays an important role in tumor generation, growth, invasion and metastasis. Meanwhile, tumor microenvironment not only facilitates the tumor infiltration, but also promotes the exchange of enzymes and cytokines to aid tumor proliferation, differentiation and self-renewal. Thus, better understanding of tumor microenvironment shows great importance. Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. Nanoparticles were suggested to show enhanced efficacy, while simultaneously reducing side effects and promoting bioavailability, owing to properties such as tumor localization and active cellular uptake. Additionally, nanoparticle surface chemistry has evolved from conventional synthetic polymers to more biologically inspired strategies, including cell membrane and self-recognition peptides, to minimize nonspecific uptake of nanoparticles. In the current review, we highlight the targets in tumor microenvironment and the strategies of nano drug delivery system to target tumor microenvironment for the treatment of cancer. We also highlight design considerations to improve nano drug delivery.
ABSTRACT
The development of hepatocellular carcinoma is insidious and rapid.Most patients can not undergo surgery after diagnosis.Transcatheter arterial chemoembolization (TACE) is considered to be the best modality for treatment of advanced hepatocellular carcinoma.However,there are some bottlenecks in TACE,such as low targeting of chemotherapy drugs and incomplete treatment.How to improve the curative effect of TACE has become a key issue in the interventional treatment of hepatocellular carcinoma.In recent years,the study of nano-drug delivery systems has been expected to solve these problems,and has become a hot spot in the field of targeted therapy for hepatocellular carcinoma.In this paper,the current research status of nano-drug delivery systems and its application in the interventional-targeted therapy of hepatocellular carcinoma are reviewed.