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.

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.

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.

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.

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.

Corrigendum: Eupafolin Suppresses Esophagus Cancer Growth by Targeting T-LAK Cell-Originated Protein Kinase Protein Kinase.

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Stealth Polydopamine-Based Nanoparticles with Red Blood Cell Membrane for the Chemo-Photothermal Therapy of Cancer.

Herein, we developed curcumin (Cur)-loaded porous poly(lactic-co-glycolic acid) (pPLGA) nanoparticles (NPs) by the nanoprecipitation method. Dopamine (DA) was then self-polymerized to form a polydopamine (PDA) layer on the surface of the NPs, yielding Cur@pPLGA/PDA NPs that are able to act as both chemotherapeutic and photothermal agents. These NPs were further camouflaged with the red blood cell membrane (RBCM) to construct RBCM-Cur@pPLGA/PDA NPs. The RBCM-pPLGA/PDA NPs were around 200 nm in size and demonstrated photothermal performance in the near-infrared (NIR) region, with a potent conversion efficiency (35.2%). The blank carrier has favorable cytocompatibility, but when drug loaded the NPs can efficiently induce the death of cancer cells (particularly when combined with NIR laser treatment). Cellular uptake results revealed greater in vitro uptake of RBCM-Cur@pPLGA/PDA NPs than bare Cur@pPLGA/PDA NPs in the case of cancer cells but reduced macrophage phagocytosis. In vivo studies in mice showed that the RBCM-Cur@pPLGA/PDA NPs exhibited prolonged blood circulation times and excellent photothermal properties, allowing tumor-specific chemo-photothermal therapy. The RBCM-Cur@pPLGA/PDA NP platform presents great potential for targeted synergistic cancer treatments.

Eupafolin Suppresses Esophagus Cancer Growth by Targeting T-LAK Cell-Originated Protein Kinase.

Eupafolin is the main bioactive component extracted from the traditional Chinese medicine Ay Tsao (Artemisia vulgaris L.), and its anti-tumor activity has had been studied in previous researches. T-LAK cell-originated protein kinase (TOPK) belongs to serine/threonine protein kinase and is highly expressed in several cancer cells and tissues, such as colon cancer, lung cancer, esophagus cancer, and so on. Therefore, it was recognized as an important target for treating tumors. Nowadays, we found that eupafolin suppressed TOPK activities at the first time in vitro and in vivo. The cells study indicated that eupafolin suppressed TOPK activities in JB6 Cl41 and KYSE450 cells. Furthermore, knockdown of TOPK in KYSE450 cells decreased their sensitivities to eupafolin. The animal study showed that the injection of eupafolin in patient-derived xenograft (PDX) mouse effectively suppressed tumor growth. Histone H3 and Ki67 were reduced, and cleaved caspase 3 was increased in tumor tissues after eupafolin treatment. To sum up, eupafolin as an TOPK inhibitor can suppress growth of esophagus cancer in vitro and in vivo. The TOPK downstream signaling molecule histone H3 in tumor tissues was also reduced after eupafolin treatment. In short, eupafolin can suppress growth of esophagus cancer cells as an TOPK inhibitor both in vitro and in vivo.

A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy.

BACKGROUND: It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. RESULTS: In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity. CONCLUSIONS: The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.

Erythrocyte Membrane Cloaked Curcumin-Loaded Nanoparticles for Enhanced Chemotherapy.

In this study, curcumin-loaded porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were prepared and surface modified with red blood cell membranes (RBCM) to yield biomimetic RBCM-p-PLGA@Cur NPs. The NPs displayed a visible cell-membrane structure at their exterior and had a uniform size of 162 ± 3 nm. In vitro studies showed that drug release from non-porous PLGA NPs was slow and that much of the drug remained trapped in the NPs. In contrast, release was accelerated from the porous PLGA NPs, and after the RBCM coating, a sustained release over 48 h was obtained. Confocal microscopy and flow cytometry results revealed that the RBCM-p-PLGA NPs led to a greater cellular uptake by H22 hepatocarcinoma cells than the uncoated analogue NPs, but could avoid phagocytosis by macrophages. The drug-free formulations were highly biocompatible, while the drug-loaded systems were effective in killing cancer cells. RBCM-p-PLGA@Cur NPs possess potent anti-tumor activity in a murine H22 xenograft cancer model (in terms of reduced tumor volume and mass, as well as inducing apoptosis of tumor cells), and have no observable systemic toxicity. Overall, our study demonstrates that the use of the RBCM to cloak nanoscale drug delivery systems holds great promise for targeted cancer treatment, and can ameliorate the severe side effects currently associated with chemotherapy.

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

BACKGROUND: Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. RESULTS: In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. CONCLUSIONS: Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

Pluronic F127-based micelles for tumor-targeted bufalin delivery.

In this study, we developed novel thermal and redox-responsive micelles based on the Pluronic F127 tri-block copolymer and employed these for redox-responsive intratumor release of bufalin, an anti-cancer drug. Pluronic F127 was first functionalized with carboxylate groups, and then assembled into micelles. The HOOC-F127-COOH micelles are 20 ±â€¯4 nm in size at 37 °C, but expand to 281 ±â€¯5 nm when cooled to 4 °C. This allows for the free diffusion of bufalin into the micellar cores at low temperatures, while at 37 °C the micelles are much more compact and the drug molecules can be effectively held in their interiors. A high encapsulation efficiency and loading content were obtained via drug incorporation at 4 °C. The drug-loaded micelles were cross-linked with cystamine, which contains a disulfide bond responsive to the local cancer microenvironment. In vitro studies showed that drug release from the cross-linked micelles was low under normal physiological conditions, but markedly accelerated upon exposure to conditions representative of the intracellular tumor environment. Confocal microscopy revealed that the cross-linked micelles gave high levels of drug release inside the cells. In vivo studies in mice showed the drug-loaded cross-linked micelles have potent anti-tumor activity, leading to high levels of apoptosis of tumor cells and significant reductions in tumor volume. The drug-loaded cross-linked micelles did not significantly influence body weight, and there was no evidence for detrimental off-target effects. These results indicate that the Pluronic-based micelles developed in this work are promising drug delivery systems for the targeted treatment of cancer.

l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells.

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles based on phenylboronic acid and N-vinylcaprolactam for insulin delivery.

Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid (AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and structure of the polymer were examined by Fourier Transform infrared spectroscopy (FT-IR) and (1)H-NMR. Dynamic light scattering (DLS), lower critical solution temperature (LCST) and transmission electron microscopy (TEM) were utilized to characterize the nanoparticles, CD spectroscopy was used to determine if there were any changes to the conformation of the insulin, and cell and animal toxicity were also investigated. The prepared nanoparticles were found to be monodisperse submicron particles and were glucose- and temperature-sensitive. In addition, the nanoparticles have good insulin-loading characteristics, do not affect the conformation of the insulin and show low-toxicity to cells and animals. These p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other hypoglycemic protein delivery.