The development of nanocarriers for natural products.

Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Pharmacology of bioactive compounds from plant extracts for improving non-alcoholic fatty liver disease through endoplasmic reticulum stress modulation: A comprehensive review.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.

Environmental stimulus-responsive mesoporous silica nanoparticles as anticancer drug delivery platforms.

Currently, cancer poses a significant health challenge in the medical community. Traditional chemotherapeutic agents are often accompanied by toxic side effects and limited therapeutic efficacy, restricting their application and advancement in cancer treatment. Therefore, there is an urgent need for developing intelligent drug release systems. Mesoporous silica nanoparticles (MSNs) have many advantages, such as a large specific surface area, substantial pore volume and size, adjustable mesoporous material pore size, excellent biocompatibility, and thermodynamic stability, making them ideal carriers for drug delivery and release. Additionally, they have been widely used to develop novel anticancer drug carriers. Recently, MSNs have been employed to design responsive systems that react to the tumor microenvironment and external stimuli for controlled release of anticancer drugs. This includes factors within the intratumor environment, such as pH, temperature, enzymes, and glutathione as well as external tumor stimuli, such as light, magnetic field, and ultrasound, among others. In this review, we discuss the research progress on environmental stimulus-responsive MSNs in anticancer drug delivery systems, including internal and external environment single stimulus-responsive release and combined stimulus-responsive release. We also summarize the current challenges associated with environmental stimulus-responsive MSNs and elucidate future directions, providing a reference for the functionalization modification and practical application of these MSNs.

Research progress on the anticancer activity of plant polysaccharides.

Tumor is a serious threat to human health, with extremely high morbidity and mortality rates. However, tumor treatment is challenging, and the development of antitumor drugs has always been a significant research focus. Plant polysaccharides are known to possess various biological activities. They have many pharmacological properties such as immunomodulation, antitumor, antiviral, antioxidative, antithrombotic, and antiradiation effects, reduction of blood pressure and blood sugar levels, and protection from liver injury. Among these effects, the antitumor effect of plant polysaccharides has been widely studied. Plant polysaccharides can inhibit tumor proliferation and growth by inhibiting tumor cell invasion and metastasis, inducing cell apoptosis, affecting the cell cycle, and regulating the tumor microenvironment. They also have the characteristics of safety, high efficiency, and low toxicity, which can alleviate, to a certain extent, the adverse reactions caused by traditional tumor treatment methods such as surgery, radiotherapy, and chemotherapy. Therefore, this paper systematically summarizes the direct antitumor effects of plant polysaccharides, their regulatory effects on the tumor microenvironment, and intervening many common high-incidence tumors in other ways. It also provides data support for the administration of plant polysaccharides in modern tumor drug therapy, enabling the identification of new targets and development of new drugs for tumor therapy.

Dual effects of endogenous formaldehyde on the organism and drugs for its removal.

Endogenous formaldehyde (FA) is produced in the human body via various mechanisms to preserve healthy energy metabolism and safeguard the organism. However, endogenous FA can have several negative effects on the body through epigenetic alterations, including cancer growth promotion; neuronal, hippocampal and endothelial damages; atherosclerosis acceleration; haemopoietic stem cell destruction and haemopoietic cell production reduction. Certain medications with antioxidant effects, such as glutathione, vitamin E, resveratrol, alpha lipoic acid and polyphenols, lessen the detrimental effects of endogenous FA by reducing oxidative stress, directly scavenging endogenous FA or promoting its degradation. This study offers fresh perspectives for managing illnesses associated with endogenous FA exposure.

Increased expression levels of DLX5 inhibit the development of the nervous system.

INTRODUCTION: Preeclampsia is a hypertensive disorder of pregnancy. DLX5 plays an important role in the migration and differentiation of subglobus pallidus precursor cells. METHODS: We established a zebrafish line expressing high levels of DLX5 and investigated changes in behavior and development of the nervous system. RESULTS: The ratios of brain volume area to whole body area at 96 hpf zebrafish in the experimental group (gRNA + CasRx) were significantly lower than the WT group and the negative control group (casRx) (P < 0.01). Behavioral trajectory distances and movement speeds exhibited by the 6th day of development in zebrafish in the experimental group (gRNA + CasRx) were significantly shorter (P < 0.01) and lower (P < 0.05) than the negative control group (gRNA + CasRx), respectively. CONCLUSIONS: Data suggested that the increased expression levels of DLX5 can inhibit brain volume development and behavioral activities in zebrafish. Maybe the high expression levels of DLX5 in the pathological state of preeclampsia can inhibit the development of the nervous system in offspring.

Research Progress on Stimulus-Responsive Polymer Nanocarriers for Cancer Treatment.

As drug carriers for cancer treatment, stimulus-responsive polymer nanomaterials are a major research focus. These nanocarriers respond to specific stimulus signals (e.g., pH, redox, hypoxia, enzymes, temperature, and light) to precisely control drug release, thereby improving drug uptake rates in cancer cells and reducing drug damage to normal cells. Therefore, we reviewed the research progress in the past 6 years and the mechanisms underpinning single and multiple stimulus-responsive polymer nanocarriers in tumour therapy. The advantages and disadvantages of various stimulus-responsive polymeric nanomaterials are summarised, and the future outlook is provided to provide a scientific and theoretical rationale for further research, development, and utilisation of stimulus-responsive nanocarriers.

A multifunctional nanocomposite coated with a BSA membrane for cascaded nitric oxide therapy.

Gas therapy based on nitric oxide (NO) has emerged as a potential therapeutic approach for cancer, and in conjunction with multi-mode combination therapy, offers new possibilities for achieving significant hyperadditive effects. In this study, an integrated AI-MPDA@BSA nanocomposite for diagnosis and treatment was constructed for PDA based photoacoustic imaging (PAI) and cascade NO release. Natural NO donor L-arginine (L-Arg) and photosensitizer (PS) IR780 were loaded into mesoporous polydopamine (MPDA). Bovine serum albumin (BSA) was conjugated to the MPDA to increase the dispersibility and biocompatibility of the nanoparticles, as well as to serve as a gatekeeper controlling IR780 release from the MPDA pores. The AI-MPDA@BSA produced singlet oxygen (1O2) and converted it into NO through a chain reaction based on L-Arg, enabling a combination of photodynamic therapy and gas therapy. Moreover, due to the photothermal properties of MPDA, the AI-MPDA@BSA performed good photothermal conversion, which allowed photoacoustic imaging. As expected, both in vitro and in vivo studies have confirmed that the AI-MPDA@BSA nanoplatform has a significant inhibitory effect on cancer cells and tumors, and no apparent systemic toxicity or side effects were detected during the treatment period.

Application of Polymer Materials in Targeting Glioma.

Glioma is a serious life-threatening disease, and traditional treatments have little effect. In recent decades, polymer materials have been developed for the treatment of glioma as a new research area. The ability to target reactive polymeric carriers is important for treating glioma. Polymer materials have good designability and expansibility. They respond to different stimuli, leading to a change in the macroscopic properties of materials. Sensitive polymer carriers respond to biological stimuli (pH, oxidative stress, enzyme, temperature, ions and nucleic acids) and the tumour microenvironment. They can be used as intelligent polymer carriers to transport chemotherapy and imaging drugs for glioma treatment. The ability of these polymer carriers to control the release of molecules at tumour-specific sites has aroused great interest. This review summarizes current research on sensitive polymer-carriers for glioma treatment over the past decade, focusing on their clinical application prospects. Finally, future applications of polymer carriers in nanomedicine are reviewed.

Nanomaterials Respond to Lysosomal Function for Tumor Treatment.

The safety and efficacy of tumor treatment are difficult problems to address. Recently, lysosomes have become an important target for tumor treatment because of their special environment and function. Nanoparticles have unique physicochemical properties which have great advantages in tumor research. Therefore, in recent years, researchers have designed various types of nanoparticles to treat tumors based on lysosomal function and environment. In this review, we summarize and analyze different perspectives of tumor treatment, including direct destruction of lysosomes or lysosomal escape, drug delivery by nanoparticles, response to endogenous or exogenous stimuli, and the targeting of tumor cells or other cells. We describe the advantages and disadvantages of these approaches as well as the developmental prospects in this field. We hope to provide new ideas for better tumor treatment.

Recent advances of the nanocomposite hydrogel as a local drug delivery for diabetic ulcers.

Diabetic ulcer is a serious complication of diabetes. Compared with that of healthy people, the skin of patients with a diabetic ulcer is more easily damaged and difficult to heal. Without early intervention, the disease will become increasingly serious, often leading to amputation or even death. Most current treatment methods cannot achieve a good wound healing effect. Numerous studies have shown that a nanocomposite hydrogel serves as an ideal drug delivery method to promote the healing of a diabetic ulcer because of its better drug loading capacity and stability. Nanocomposite hydrogels can be loaded with one or more drugs for application to chronic ulcer wounds to promote rapid wound healing. Therefore, this paper reviews the latest progress of delivery systems based on nanocomposite hydrogels in promoting diabetic ulcer healing. Through a review of the recent literature, we put forward the shortcomings and improvement strategies of nanocomposite hydrogels in the treatment of diabetic ulcers.

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a multifaceted clinicopathological syndrome characterised by excessive hepatic lipid accumulation that causes steatosis, excluding alcoholic factors. Platelet-activating factor (PAF), a biologically active lipid transmitter, induces platelet activation upon binding to the PAF receptor. Recent studies have found that PAF is associated with gamma-glutamyl transferase, which is an indicator of liver disease. Moreover, PAF can stimulate hepatic lipid synthesis and cause hypertriglyceridaemia. Furthermore, the knockdown of the PAF receptor gene in the animal models of NAFLD helped reduce the inflammatory response, improve glucose homeostasis and delay the development of NAFLD. These findings suggest that PAF is associated with NAFLD development. According to reports, patients with NAFLD or animal models have marked platelet activation abnormalities, mainly manifested as enhanced platelet adhesion and aggregation and altered blood rheology. Pharmacological interventions were accompanied by remission of abnormal platelet activation and significant improvement in liver function and lipids in the animal model of NAFLD. These confirm that platelet activation may accompany a critical importance in NAFLD development and progression. However, how PAFs are involved in the NAFLD signalling pathway needs further investigation. In this paper, we review the relevant literature in recent years and discuss the role played by PAF in NAFLD development. It is important to elucidate the pathogenesis of NAFLD and to find effective interventions for treatment.

Cu2+-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy.

In this study, a pH-responsive controlled-release mesoporous silica nanoparticle (MSN) formulation was developed. The MSNs were functionalized with a histidine (His)-tagged targeting peptide (B3int) through an amide bond, and loaded with an anticancer drug (cisplatin (CP)) and a lysosomal destabilization mediator (chloroquine (CQ)). Cu2+ was then used to seal the pores of the MSNs via chelation with the His-tag. The resultant nanoparticles showed pH-responsive drug release, and could effectively target tumor cells via the targeting effect of B3int. The presence of CP and Cu2+ permits reactive oxygen species to be generated inside cells; thus, the chemotherapeutic effect of CP is augmented by chemodynamic therapy. In vitro and in vivo experiments showed that the nanoparticles are able to effectively kill tumor cells. An in vivo cancer model revealed that the nanoparticles increase apoptosis in tumor cells, and thereby diminish the tumor volume. No off-target toxicity was noted. It thus appears that the functionalized MSNs developed in this work have great potential for targeted, synergistic anticancer therapies.

Literature Review on the Use of Herbal Extracts in the Treatment of Non- Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease is a common chronic liver injury disease, and its incidence is rapidly increasing across the globe, thus becoming a serious threat to human health. So far, the clinical prevention and treatment of non-alcoholic fatty liver disease mainly include single-targeted drug therapy, surgical treatment and lifestyle changes. However, these treatments cannot completely address the complex pathogenesis of non-alcoholic fatty liver disease and have various side effects. Recent studies reveal that many herbal extracts are found to have potential anti-non-alcoholic fatty liver disease activities. OBJECTIVE: This paper presents a review on herbal extracts used for the treatment of non-alcoholic fatty liver disease in experimental studies to provide a theoretical basis for their clinical application in the treatment of non-alcoholic fatty liver disease and for new drug development. METHODS: Scientific papers were retrieved by searching the PubMed database up to Feb 2021 using the following keywords: 'non-alcoholic fatty liver disease', 'herbal extracts' ('flavonoids', 'saponins', 'quinones', 'phenolic compounds', 'alkaloids', 'polysaccharides', 'ginkgolide B', 'schizandrin B', 'ursolic acid') and 'mechanism'. RESULTS: The pharmacological effects and mechanisms of many herbal extracts can reverse the adverse health effects of non-alcoholic fatty liver disease. CONCLUSION: In vitro and in vivo experimental studies indicated that herbal extracts can improve the symptoms of non-alcoholic fatty liver disease by inhibiting inflammation, antioxidant stress, improvement of lipid metabolism and insulin sensitivity and regulating intestinal bacteria flora. However, there needs to be sufficient data from human clinical trials to prove their efficacy and safety.

Construction of Biomimetic-Responsive Nanocarriers and their Applications in Tumor Targeting.

BACKGROUND: At present, tumors are leading cause of death. Biomimetic nanocarriers for precision cancer therapy are attracting increasing attention. Nanocarriers with a good biocompatible surface could reduce the recognition and elimination of nanoparticles as foreign substances by the immune system, offer specific targeting, and improve the efficacy of precision medicine for tumors, thereby providing outstanding prospects for application in cancer therapy. In particular, cell membrane biomimetic camouflaged nanocarriers have become a research hotspot because of their excellent biocompatibility, prolonged circulation in the blood, and tumor targeting. OBJECTIVE: The objective of this study is to summarize the biological targeting mechanisms of different cell membraneencapsulated nanocarriers in cancer therapy. In this article, the characteristics, applications, and stages of progress of bionic encapsulated nanocarriers for different cell membranes are discussed, as are the field's developmental prospects. METHODS: The findings on the characteristics of bionic encapsulated nanocarriers for different cell membranes and tumor treatment have been analyzed and summarized. RESULTS: Biomimetic nanosystems based on various natural cell and hybrid cell membranes have been shown to efficiently control targeted drug delivery systems. They can reduce immune system clearance, prolong blood circulation time, and improve drug loading and targeting, thereby enhancing the diagnosis and treatment of tumors and reducing the spread of CTCs. CONCLUSION: With advances in the development of biomimetic nanocarrier DDSs, novel ideas for tumor treatment and drug delivery have been emerged. However, there are still some problems in biomimetic nanosystems. Therefore, it needs to be optimized through further research, from the laboratory to the clinic to benefit a wide range of patients.

Herbal Nanoformulations for Asthma Treatment.

BACKGROUND: In recent decades, the prevalence of asthma has substantially increased worldwide. Advances in phytochemistry and phytopharmacology have clarified the active ingredients and biological activities of medicinal plant products for treating asthma, and the role of herbal therapies in asthma treatment has become increasingly evident. However, most plant extracts have low solubility and poor stability of bioactive components, resulting in low bioavailability and loss of efficacy. Owing to these shortcomings, the clinical use of many herbal extracts is limited. OBJECTIVE: To summarise and analyse the characteristics of herbal nanoformulations and their application in asthma treatment. The objective of this review article is to address the emerging trends of herbal nanoformulations for an effective treatment of asthma. METHODS: Various research and review articles from reputed international journals were referred to and compiled. RESULTS: The nano-sized herbal formulations improve the solubility and bioavailability of herbal medicines and contribute to the sustained release of drugs, thus, increasing the therapeutic applications of herbal extracts. The review present different types of herbal nanoformulations, including micelles, nanoparticles, solid lipid nanoparticles, lipid-based liquid crystalline nanoparticles and nanoemulsions, which are potential nanodrugs for asthma treatment. CONCLUSIONS: Herbal nanoformulations have shown great prospects for the treatment of asthma in recent years. More safety and toxicity data are still needed to promote their development and application.

Novel glucose-responsive nanoparticles based on p-hydroxyphenethyl anisate and 3-acrylamidophenylboronic acid reduce blood glucose and ameliorate diabetic nephropathy.

An insulin delivery system that self-regulates blood sugar levels, mimicking the human pancreas, can improve hyperglycaemia. At present, a glucose-responsive insulin delivery system combining AAPBA with long-acting slow release biomaterials has been developed. However, the safety of sustained-release materials and the challenges of preventing diabetic complications remain. In this study, we developed a novel polymer slow release material using a plant extract-p-hydroxyphenylethyl anisate (HPA). After block copolymerisation with AAPBA, the prepared nanoparticles had good pH sensitivity, glucose sensitivity, insulin loading rate and stability under physiological conditions and had high biocompatibility. The analysis of streptozotocin-induced diabetic nephropathy (DN) mouse model showed that the insulin-loaded injection of nanoparticles stably regulated the blood glucose levels of DN mice within 48 â€‹h. Importantly, with the degradation of the slow release material HPA in vivo, the renal function improved, the inflammatory response reduced, and antioxidation levels in DN mice improved. This new type of nanoparticles provides a new idea for hypoglycaemic nano-drug delivery system and may have potential in the prevention and treatment of diabetic complications.

Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications.

BACKGROUND: Diabetes complications are the leading cause of mortality in diabetic patients. The common complications are decline in antioxidant capacity and the onset of micro-inflammation syndrome. At present, glucose-responsive nanoparticles are widely used, as they can release insulin-loaded ultrafine particles intelligently and effectively reduce blood sugar. However, the toxicology of this method has not been fully elucidated. The plant extracts of pterostilbene (PTE) have a wide range of biological applications, such as antioxidation and inflammatory response improvement. Therefore, we have proposed new ideas for the cross application of plant extracts and biomaterials, especially as part of a hypoglycaemic nano-drug delivery system. RESULTS: Based on the PTE, we successfully synthesised poly(3-acrylamidophenyl boric acid-b-pterostilbene) (p[AAPBA-b-PTE]) nanoparticles (NPs). The NPs were round in shape and ranged between 150 and 250 nm in size. The NPs possessed good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin-loaded NPs was approximately 56%, and the drug loading (LC) capacity was approximately 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to changes in the glucose concentration, thus achieving an effective, sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under normal physiological conditions, NPs were completely degraded within 40 days. Fourteen days after mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, or kidney. Moreover, NPs effectively reduced blood glucose, improved antioxidant capacity and reversed micro-inflammation in mice. CONCLUSIONS: p(AAPBA-b-PTE) NPs were successfully prepared using PTE as raw material and effectively reduced blood glucose, improved antioxidant capacity and reduced the inflammatory response. This novel preparation can enable new combinations of plant extracts and biomaterials to adiministered through NPs or other dosage forms in order to regulate and treat diseases.

Polymers Based on Phenyl Boric Acid in Tumor-Targeted Therapy.

BACKGROUND: Tumors are still among the major challenges to human health. Tumor-targeted therapy is an effective way to treat tumors based on precise medical models. Sialic acid (SA) is overexpressed on the surface of tumor cells, and Phenyl Boric Acid (PBA) can specifically bind to SA. However, studies on the use of PBA in tumor-targeted therapy are few. OBJECTIVE: To summarize and analyze the characteristics and influencing factors of tumor targeted therapy in recent years, and the influencing factors of phenyl boric acid modified polymers in tumor targeted therapy, such as hydrogen ion concentration (pH), Adenosine Triphosphate (ATP), and sugars. This paper describes the application of phenyl boric acid partially functionalized nano-polymers in various types of targeted tumors, such as breast cancer, lung adenocarcinoma, liver cancer, and so forth. In order to further improve the basic research and clinical workers' understanding of nano-preparations and tumor targeted therapy. At the same time, it is also expected to promote the development value of phenyl boric acid. METHODS: The findings on tumor-targeted therapy and the role of partially functionalized polymers with PBA in different tumors at home and abroad has been analyzed and summarized in recent years. RESULTS: Tumor-targeted therapy is a promising treatment for tumors. PBA promotes the treatment of tumors using SA, which is highly expressed on the surface of tumor cells. CONCLUSION: Tumor-targeted therapy has shown great prospects for clinical application in recent years. PBA is beneficial as a member of the drug loading system. Further studies are still needed to promote its development and application.

Bioresponsive Functional Phenylboronic Acid-Based Delivery System as an Emerging Platform for Diabetic Therapy.

The glucose-sensitive self-adjusting drug delivery system simulates the physiological model of the human pancreas-secreting insulin and then precisely regulates the release of hypoglycemic drugs and controls the blood sugar. Thus, it has good application prospects in the treatment of diabetes. Presently, there are three glucose-sensitive drug systems: phenylboronic acid (PBA) and its derivatives, concanavalin A (Con A), and glucose oxidase (GOD). Among these, the glucose-sensitive polymer carrier based on PBA has the advantages of better stability, long-term storage, and reversible glucose response, and the loading of insulin in it can achieve the controlled release of drugs in the human environment. Therefore, it has become a research hotspot in recent years and has been developed very rapidly. In order to further carry out a follow-up study, we focused on the development process, performance, and application of PBA and its derivatives-based glucose-sensitive polymer drug carriers, and the prospects for the development of this field.