Erythrocyte-derived drug delivery systems in cancer therapy

As natural blood components,erythrocytes were good candidates for being used as drug delive ry systems to improve the pharmacokinetics,biocompatibility and many other aspects of different drugs.The advantages brought by erythrocytes making erythrocyte-derived drug delivery systems,also known as erythrocyte carriers,suitable for various anti-cancer agents,especially newly invented agents like nanoparticles,which were characterized by their undesired systematic toxicity,anaphylactic reactions and poor biocompatibility.Current researches on erythrocyte carriers in ca ncer therapy showed inspiring results in four major aspects:cancer enzyme therapy,delivering chemotherapeutic agents,combining with nanoparticles,and several other anti-cancer agents for gene or immune therapy.This novel delivering system was now undergoing the translation process from laboratory to clinical practice.Erythrocyte carriers for cancer enzyme therapy have entered the stage of clinical trial and have showed promising outcomes,and others were still at pre-clinical stage.In summary,erythrocyte-derived drug delivery system might play an indispensable role in the management of cancer in the future.     

Cell membrane-coated nanoparticles for immunotherapy

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and e...     

Erythrocyte membrane encapsulated gambogic acid nanoparticles as a therapeutic for hepatocellular carcinoma

Gambogic acid (GA) is a potential clinical anticancer drug that can exert antitumor effects via various molecular mechanisms. Notwithstanding, GA's low water solubility, poor stability, short half-life, and unavoidable toxic side effects have significantly hampered its clinical application. Erythrocyte membrane-coated nanoparticles (RBCM-NPs) improve drug's physicochemical properties, biocompatibility, and pharmacokinetic behaviors, allowing for long-term drug circulation and passive targeting. In this study, a novel biomimetic drug delivery system (DDS) against hepatocellular carcinoma was prepared by covering RBCM on GPP-NPs (GA-loaded mPEG-PLA NPs) to develop the RBC@GPP-NPs. In comparison to RBCM-free nanoparticles and free GA, RBC@GPP-NPs improved the drug's water solubility, stability, safety, and anti-tumor activity in vivo. We expect that this bionic nanoparticle composite can expand the clinical applicability of GA and provide a feasible solution for the research and development of GA's nano-formulation.     

Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy

Chemotherapy drugs continue to be the main component of oncology treatment research and have been proven to be the main treatment modality in tumor therapy. However, the poor delivery efficiency of cancer therapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. The recent integration of biological carriers and functional agents is expected to camouflage synthetic biomimetic nanoparticles for targeted delivery. The promising candidates, including but not limited to red blood cells and their membranes, platelets, tumor cell membrane, bacteria, immune cell membrane, and hybrid membrane are typical representatives of biological carriers because of their excellent biocompatibility and biodegradability. Biological carriers are widely used to deliver chemotherapy drugs to improve the effectiveness of drug delivery and therapeutic efficacy in vivo, and tremendous progress is made in this field. This review summarizes recent developments in biological vectors as targeted drug delivery systems based on microenvironmental stimuli-responsive release, thus highlighting the potential applications of target drug biological carriers. The review also discusses the possibility of clinical translation, as well as the exploitation trend of these target drug biological carriers.     

Chitosan Nanoparticles-Insight into Properties,Functionalization and Applications in Drug Delivery and Theranostics

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.     

Recent Advances in Oral and Transdermal Protein Delivery Systems

Protein and peptide drugs are predominantly administered by injection to achieve high bioavailability, but this greatly compromises patient compliance. Oral and transdermal drug delivery with minimal invasiveness and high adherence represent attractive alternatives to injection administration. However, oral and transdermal administration of bioactive proteins must overcome biological barriers, namely the gastrointestinal and skin barriers, respectively. The rapid development of new materials and technologies promises to address these physiological obstacles. This review provides an overview of the latest advances in oral and transdermal protein delivery, including chemical strategies, synthetic nanoparticles, medical microdevices, and biomimetic systems for oral administration, as well as chemical enhancers, physical approaches, and microneedles in transdermal delivery. We also discuss challenges and future perspectives of the field with a focus on innovation and translation.     

Organic Nanoplatforms for Iodinated Contrast Media in CT Imaging

X-ray computed tomography (CT) imaging can produce three-dimensional and high-resolution anatomical images without invasion, which is extremely useful for disease diagnosis in the clinic. However, its applications are still severely limited by the intrinsic drawbacks of contrast media (mainly iodinated water-soluble molecules), such as rapid clearance, serious toxicity, inefficient targetability and poor sensitivity. Due to their high biocompatibility, flexibility in preparation and modification and simplicity for drug loading, organic nanoparticles (NPs), including liposomes, nanoemulsions, micelles, polymersomes, dendrimers, polymer conjugates and polymeric particles, have demonstrated tremendous potential for use in the efficient delivery of iodinated contrast media (ICMs). Herein, we comprehensively summarized the strategies and applications of organic NPs, especially polymer-based NPs, for the delivery of ICMs in CT imaging. We mainly focused on the use of polymeric nanoplatforms to prolong circulation time, reduce toxicity and enhance the targetability of ICMs. The emergence of some new technologies, such as theragnostic NPs and multimodal imaging and their clinical translations, are also discussed.     

Tuning the In Vivo Transport of Anticancer Drugs Using Renal‐Clearable Gold Nanoparticles

Precise control of in vivo transport of anticancer drugs in normal and cancerous tissues with engineered nanoparticles is key to the future success of cancer nanomedicines in clinics. This requires a fundamental understanding of how engineered nanoparticles impact the targeting‐clearance and permeation‐retention paradoxes in the anticancer‐drug delivery. Herein, we systematically investigated how renal‐clearable gold nanoparticles (AuNPs) affect the permeation, distribution, and retention of the anticancer drug doxorubicin in both cancerous and normal tissues. Renal‐clearable AuNPs retain the advantages of the free drug, including rapid tumor targeting and high tumor vascular permeability. The renal‐clearable AuNPs also accelerated body clearance of off‐target drug via renal elimination. These results clearly indicate that diverse in vivo transport behaviors of engineered nanoparticles can be used to reconcile long‐standing paradoxes in the anticancer drug delivery.     

Near‐Infrared‐Controlled,Targeted Hydrophobic Drug‐Delivery System for Synergistic Cancer Therapy

Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near‐infrared (NIR)‐regulated hydrophobic drug‐delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin‐loaded AuMP‐polyethylene glycol‐folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote‐controlled hydrophobic drug‐delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR‐controlled, targeted drug‐delivery method would promote the development of high‐performance hydrophobic anticancer drug‐delivery system in future clinical applications.     

Anticancer drug-loaded gliadin nanoparticles induce apoptosis in breast cancer cells

Nanoscale drug carriers play an important role in regulating the delivery, permeability, and retention of the drugs. Although various carriers have been used to encapsulate anticancer drugs, natural biomaterials are of great benefit for delivery and controlled release of drugs. We used the electrospray deposition system to synthesize gliadin and gliadin-gelatin composite nanoparticles for delivery and controlled release of an anticancer drug (e.g., cyclophosphamide). The size profile and synthesis of nanoparticles was characterized by dynamic light scattering and X-ray diffractometry. Cyclophosphamide was gradually released from the gliadin nanoparticles for 48 h. In contrast, the gliadin-gelatin composite nanoparticles released cyclophosphamide in a rapid manner. Furthermore, we demonstrated that breast cancer cells cultured with cyclophosphamide-loaded 7% gliadin nanoparticles for 24 h became apoptotic, confirmed by Western blotting analysis. Therefore, the gliadin-based nanoparticle could be a powerful tool for delivery and controlled release of anticancer drugs.     

由聚合物门控的介孔二氧化硅基刺激响应性药物递送系统

本文主要介绍了以聚合物体系作为门控构筑的基于介孔二氧化硅纳米粒子的刺激响应性药物控释体系, 并根据聚合物类别将门控体系分为聚合物刷、 聚合物交联网络和聚合物包裹层三类. 根据聚合物“阀门”与无机纳米粒子的共价或非共价连接方式, 综述了这些杂化材料在不同外界刺激作用下的药物控制释放行为, 并给出该领域所面临的机遇和挑战.     

NIR light-induced tumor phototherapy using ICG delivery system based on platelet-membrane-camouflaged hollow bismuth selenide nanoparticles

Near-infrared (NIR) light-triggered photothermal therapy (PTT) is a promising treatment strategy for treating cancer. The combination of nanotechnology and NIR has been widely applied. However, the therapeutic efficacy of the drug-delivery system depends on their ability to avoid phagocytosis of endothelial system, cross the biological barriers, prolong circulation life, localize and rapidly release the therapeutic at target sites. In this work, we designed a platelet membrane (PM)-camouflaged hollow mesoporous bismuth selenide nanoparticles (BS NPs) loading with indocyanine green (ICG) (PM@BS-ICG NPs) to achieve the above advantages. PM-coating has active tumor-targeting ability which could prevent drug leakage and provide drug long circulation, causing drug delivery systems to accumulate in tumor sites effectively. Moreover, as a type of the photothermal sensitizers, BS NPs are used as the inner cores to improve ICG stability and are served as scaffolds to enhance the hardness of this drug delivery system. For one hand, the thermal vibration of BS NPs under NIR laser irradiation causes tumor inhibition through hyperthermia. For another hand, this hyperthermia process could damage PM and let ICG rapid release from PM@BS-ICG NPs. The in vitro and in vivo results showed that this biomimetic nano-drug delivery system exhibits obvious antitumor activity which has good application prospect.     

Perspectives and Prospective on Solid Lipid Nanoparticles as Drug Delivery Systems

Combating multiple drug resistance necessitates the delivery of drug molecules at the cellular level. Novel drug delivery formulations have made it possible to improve the therapeutic effects of drugs and have opened up new possibilities for research. Solid lipid nanoparticles (SLNs), a class of colloidal drug carriers made of lipids, have emerged as potentially effective drug delivery systems. The use of SLNs is associated with numerous advantages such as low toxicity, high bioavailability of drugs, versatility in the incorporation of hydrophilic and lipophilic drugs, and the potential for production of large quantities of the carrier systems. The SLNs and nanostructured lipid carriers (NLCs) are the two most frequently used types of nanoparticles. These types of nanoparticles can be adjusted to deliver medications in specific dosages to specific tissues, while minimizing leakage and binding to non-target tissues.     

Oral delivery of polyester nanoparticles for brain-targeting: Challenges and opportunities

Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This review article firstly describes the main obstacles faced by oral administered brain targeting, including:(1)instability in the gastrointestinal tract;(2) poor penetration of the intestinal mucosa and epithelium;(3)blood clearance; and(4) restriction by the BBB. Then the key factors infl...     

A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected Macrophages Using Biodegradable Nanoparticles

Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing death of more than 10 million people. Because of the development of drug-resistant TB, drug delivery to the infected site through nanoparticle had been studied for long time. Nanoparticles indicate different sorts of association with the natural particles of the body. Nanoparticles can be used as controlled or specific drug delivery system. It can be through temporal controlled or can be distribution controlled. Glucose polymer-based nanoparticles might play an important role as drug delivery system in case of targeted drug delivery in the infected site of the body or in infected macrophages, as they are biodegradable so there should not be any side effects of these particles in the body and also they show very slow immune response. CD4, Beta 1, TGFb-1, IL-2, IL-13 SEC14L1, GUSB, BPI, and CCR7 are major biomarkers secreted after infection of this bacterium by the macrophages which can be used for targeted drug delivery in infected macrophages. As these markers can be used for delivery of drugs at destined position, they can be very beneficial in reducing toxicities of antituberculer drugs to the other uninfected sites and in operating only the infected macrophages.     

Recent Advances of Cell Membrane Coated Nanoparticles in Treating Cardiovascular Disorders

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.     

Cellular Membrane Components-Mediated Cancer Immunotherapeutic Platforms

Immune cell engineering is an active field of ongoing research that can be easily applied to nanoscale biomedicine as an alternative to overcoming limitations of nanoparticles. Cell membrane coating and artificial nanovesicle technology have been reported as representative methods with an advantage of good biocompatibility for biomimetic replication of cell membrane characteristics. Cell membrane-mediated biomimetic technique provides properties of natural cell membrane and enables membrane-associated cellular/molecular signaling. Thus, coated nanoparitlces (NPs) and artificial nanovesicles can achieve effective and extended in vivo circulation, enabling execution of target functions. While coated NPs and artificial nanovesicles provide clear advantages, much work remains before clinical application. In this review, first a comprehensive overview of cell membrane coating techniques and artificial nanovesicles is provided. Next, the function and application of various immune cell membrane types are summarized.     

Synergistic cytotoxic effect of different sized ZnO nanoparticles and daunorubicin against leukemia cancer cells under UV irradiation

Failure of chemotherapy to the malignant tumor is usually induced by multidrug resistance (MDR). The development of anti-MDR agents for efficient drug delivery is of great importance in cancer therapy. Recent reports have demonstrated that some anticancer drugs could be readily self-assembled on some biocompatible nanomaterials covalently or non-covalently, which could effectively afford the sustained drug delivery for the target cancer cells and reduce the relevant toxicity towards normal cells and tissues. Thus these biocompatible nanomaterials may play an important role in the relevant biological and biomedical system. In this paper, we have explored the cytotoxic effect of anticancer drug daunorubicin on leukemia cancer cells in the absence and presence of different sized ZnO nanoparticles via fluorescence microscopy, UV-Vis absorption spectroscopy, electrochemical analysis as well as MTT assay. Meanwhile, the cytotoxicity suppression of daunorubicin together with different sized ZnO nanoparticles in the absence and presence of UV irradiation on leukemia cancer cells were also investigated using MTT assay. The results indicate that the combination of the different sized ZnO nanoparticles and daunorubicin under UV irradiation could have synergistic cytotoxic effect on leukemia cancer cells, indicating the great potential of ZnO nanoparticles in relevant clinical and biomedical applications.     

New advances in gated materials of mesoporous silica for drug controlled release

Drug delivery systems (DDS) are used to deliver therapeutic drugs to improve selectivity and reduce side effects. With the development of nanotechnology, many nanocarriers have been developed and applied to drug delivery, including mesoporous silica. Mesoporous silica nanoparticles (MSNs) have attracted a lot of attention for simple synthesis, biocompatibility, high surface area and pore volume. Based on the pore system and surface modification, gated mesoporous silica nanoparticles can be designed to realize on-command drug release, which provides a new approach for selective delivery of antitumor drugs. Herein, this review mainly focuses on the “gate keepers” of mesoporous silica for drug controlled release in nearly few years (2017–2020). We summarize the mechanism of drug controlled release in gated MSNs and different gated materials: inorganic gated materials, organic gated materials, self-gated drug molecules, and biological membranes. The facing challenges and future prospects of gated MSNs are discussed rationally in the end.     

Advances in Exosomes‐Based Drug Delivery Systems

Exosomes, a subgroup of extracellular vesicles, are important mediators of long‐distance intercellular communication and are involved in a diverse range of biological processes such as the transport of lipids, proteins, and nucleic acids. Researchers, seeing the problems caused by the toxic effects and clearance of synthetic nanoparticles, consider exosomes as an interesting alternative to such nanoparticles in the specific and controlled transport of drugs. In recent years, there have been remarkable advances in the use of exosomes in cancer therapeutics or for treating neurological diseases, among other applications. The objective of this work is to analyze studies focused on exosomes used in drug delivery system, present and future applications in this field of research are discussed based on the results obtained.