ABSTRACT
Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.
ABSTRACT
Cancer is considered as one of the major diseases endangering human health in the world, it is urgent to find a safer and more efficient treatment for cancer therapy. Gene therapy with ribonucleic acid (RNA) drugs could regulate the expression of tumor related genes, and exhibit good anti-tumor therapeutic potential in preclinical and clinical trials. Based on the differences between tumor tissues and normal tissues in microenvironment signal characteristics such as pH, specific enzyme concentration or redox gradient, various microenvironment responsive nanocarriers had been studied and developed to deliver RNA drugs to tumor tissues and cells, improving the anti-tumor efficacy of RNA drugs and reducing toxic and side effects. This paper reviews the pathophysiological characteristics of tumor microenvironment and various strategies of tumor microenvironment responsive nanocarriers, in order to provide reference for the design of safe and efficient RNA drug delivery system for cancer therapy.
ABSTRACT
Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.
ABSTRACT
Induction of immunogenic cell death promotes antitumor immunity against cancer. However, majority of clinically-approved drugs are unable to elicit sufficient ICD. Here, our study revealed that mitochondria-targeted delivery of doxorubicin (DOX) massively amplified ICD via substantial generation of reactive oxygen species (ROS) after mitochondrial damage. The underlying mechanism behind increased ICD was further demonstrated to be ascribed to two pathways: (1) ROS elevated endoplasmic reticulum (ER) stress, leading to surface exposure of calreticulin; (2) ROS promoted release of various mitochondria-associated damage molecules including mitochondrial transcription factor A. Nevertheless, adaptive upregulation of PD-L1 was found after such ICD-inducing treatment. To overcome such immunosuppressive feedback, we developed a tumor stimuli-responsive nano vehicle to simultaneously exert mitochondrial targeted ICD induction and PD-L1 blockade. The nano vehicle was self-assembled from ICD-inducing copolymer and PD-L1 blocking copolymer, and possessed long-circulating property which contributed to better tumor accumulation and mitochondrial targeting. As a result, the nano vehicle remarkably activated antitumor immune responses and exhibited robust antitumor efficacy in both immunogenic and non-immunogenic tumor mouse models.
ABSTRACT
During growth and progression, the microenvironment of tumors suffers a series of abnormal characteristics, which include hypoxia, acid pH, increased oxidative stress, excess glutathione (GSH), as well as certain overexpressed enzymes. Although affect or limit the cancer therapeutic outcomes, these factors provide possible approaches to strategies for cancer detection and novel therapy at the same time. Recently, based on these properties of the tumor microenvironment (TME), various kinds of responsive nano-platforms have been continuously developed and applied in cancer theranostics preliminarily. Thus, this review would introduce the typical features of TME firstly, then detailly summarize the design principles and research progress of corresponding hypoxia-responsive, pH-responsive, redox-responsive, enzyme-responsive, dual-responsive and multi-responsive nano-platforms. Finally, the challenges and the perspectives of the TME-responsive nano-platforms are briefly discussed.
ABSTRACT
Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd
ABSTRACT
In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.
ABSTRACT
Nanotechnology has become an outgrowing field in novel drug delivery system. It confers several merits overconventional formulations like increased solubility and bioavailability, targeted drug delivery and a decreaseddose of the drug. The selection of appropriate method for the preparation of nanoparticulate system depends on thephysicochemical characteristics of the drug to be loaded and polymer. This review has covered the most widelyacceptable preparation techniques for polymeric and lipidic nanoparticles including nanoprecipitation, milling,extrusion, supercritical fluid technology, salting out, gelation, sonication, high-pressure homogenization, and solventemulsification methods. Nanocarriers, the traditional nano-formulation drug delivery systems, encountered somemajor problems in process scale-up, reproducibility, and stability during storage. To circumvent these problems a newapproach has emerged which are “In situ or self-assembled nanoparticles drug delivery system.” Such approachescomprise experimentation with different types of polymers, surfactants or novel process in order to prepare a preconcentrate of drug formulation, which on entering into an aqueous medium (gastrointestinal fluid, blood) will formnanoparticles. The in situ nanoformulations can be the futuristic approach in nanocarriers to overcome the problemsassociated with the scale-up process and also minimize the cost of production. This review focuses on differentpreparation techniques for polymeric and lipidic nanocarriers preparation, in situ nanoformulation approaches andrelease characteristics of stimuli responsive nanoformulation
ABSTRACT
Polymer-drug conjugates (PDCs) have been extensively studied as nanocarriers for anti-tumor drugs delivery due to excellent stability in circulation and high drug loading ability. Stimuli-responsive PDCs(SRPDCs) could release the loading drug in response to various intra-or extracellular biological stimulis (eg, acidic pH, altered redox potential, and upregulated enzyme), as well as external artificial stimulis (eg, magnetic feld, light, temperature, and ultrasound), which are considered as "smart" nanocarriers for delivery of anti-tumor drugs. In this article, recent progresses in the development of SRPDCs for cancer therapy are reviewed, covering the design, smart linkages as well as responsive drug release property, so as to provide reference for the development of related drug delivery systems. In order to improve the successful translation of stimuli-responsive PDCs, drawbacks and limitations of current researches are discussed, besides, future perspectives and research strategies are also provided.
ABSTRACT
Immunotherapy has emerged as one of the major modalities for clinical cancer therapy, along with surgery, chemotherapy, radiotherapy and targeted therapy. However, tumor-targeted delivery of immune therapeutics is challenged by a series of barriers including non-specific release, poor tumor penetration capacity, and insufficient cellular uptake of the therapeutic regimens, which seriously restricted the efficiency and efficacy of immunotherapy. To address above challenges, nanosized drug delivery systems (NDDS) have been extensively exploited to achieve tumor-targeted delivery of immunotherapy drugs. It has been well investigated that solid tumors are of unique characteristics including acidic, hypoxic and enzymatic extracellular microenvironment. Meanwhile, the tumor cells are of acidic, reductant and reactive oxygen species intracellular microenvironment. In recent years, a large variety of tumor microenvironment-activatable NDDS have been exploited to respond specifically to the stimulus of extracellular or intracellular tumor microenvironment for enhancing the accumulation, retention and penetration in the tumor tissue. These NDDS were also employed to promote intracellular uptake and tunable drug release inside the tumor cells. In this review article, we summarized the recent progress of our laboratory using the tumor microenvironment-activatable NDDS for immune efficient therapeutics delivery, and improved cancer immunotherapy. We also briefly discussed the challenges and provided perspective of NDDS-based cancer immunotherapy.
ABSTRACT
The drug delivery system with "gatekeeper" is designed to achieve a stable entrapment state of the payload under normal physiological conditions through the gatekeepers. With tumor microenvironment or stimulation of exogenous factors, the gatekeeper is detached or altered to promote the responsive release of the drug. In this paper, we focus on applications of stimuli-responsive linkages and stimuli-responsive groups, and review research progresses of drug delivery system with "gatekeeper" developed over the past 10 years.
ABSTRACT
In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuliresponsive mesoporous silica nano drug delivery systems in tumor therapy were summarized.
ABSTRACT
@#With the rapid development of nanotechnology and in-depth understanding of tumor microenvironment, stimuli-responsive smart drug delivery nanosystem based on tumor microenvironment(TME)has received extensive attention. TME-responsive smart delivery nanosystem can transport antitumor drug in circulation stably, after arriving in tumor tissue or targeted cells, the structure of nanocarriers changes under the stimuli of TME. Improved drug concentrations in targeted site significantly increase the antitumor efficiency and reduce the side effects of drugs. The stimulating factors in the TME include pH, redox potential, enzyme, reactive oxygen species(ROS), adenosine-5′-triphosphate(ATP)and so on. This review mainly gives a comprehensive overview in the latest research and new development in TME-responsive smart drug delivery nanosystems for efficient tumor therapy, mainly based on pH response type, enzyme response, reduction response, ROS response, and ATP response smart drug delivery nanosystems. Moreover, research directions in the future are pointed out in this review.
ABSTRACT
The current prevalence of cancer chemotherapy drugs is inefficient and highly toxic, thus selecting the appropriate new forms of cancer treatment has become one of the important tasks. On the basis of domestic and foreign research literature, cutline the composition, characteristics and main preparation methods of polymeric micelles. Introduced varieties of stimuli-responsive polymer micelles, as well as targeted polymeric micelles used as an anticancer drug carrier. By making use of inside microenvironment of tumor cells, the preparation of various of new intelligent polymeric micelles with slight side effects and good treatment in virto and in vivo, can achieve effective control of drug release, which has great development and prospect in application.
ABSTRACT
Controlled drug delivery is useful because it allows to obtain better drug product effectiveness, reliability and safety. Interest in stimuli-responsive polymers is steadily gaining increasing momentum especially in the fields of controlled and self-regulated drug delivery. Stimuliresponsive or “smart“ polymers are macromolecules that display a significant physiochemical change in response to small changes in their environment such as temperature, pH, light, magnetic field, ionic factors, etc. The changes are reversible, and therefore, the smart polymers are capable of returning to its initial state as soon as the trigger is removed. They have become one important class of polymers and their applications have been increasing significantly in the last three decades. Smart polymers have very promising applications in the biomedical field as delivery systems of therapeutic agents, tissue engineering scaffolds, cell culture supports, bioseparation devices, etc. The versatility and untapped potential of smart polymeric materials makes them one of the most promising interfaces of chemistry and biology.