CircRHBDD1 promotes immune escape via IGF2BP2/PD-L1 signaling and acts as a nanotherapeutic target in gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. METHODS: The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. RESULTS: We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. CONCLUSION: Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

ACYP2 functions as an innovative nano-therapeutic target to impede the progression of hepatocellular carcinoma by inhibiting the activity of TERT and the KCNN4/ERK pathway.

An increasing body of evidence suggests that acylphosphatase-2 (ACYP2) polymorphisms are correlated with an increased susceptibility to a range of malignancies. Nevertheless, its potential functions, molecular mechanisms in hepatocellular carcinoma (HCC) and whether it can be act as a therapeutic target remain uninvestigated. Herein, ACYP2 was found to be lowly expressed in HCC and was negatively correlated with tumor size, tumor differentiation, microvascular invasion and the prognosis of HCC patients. Functional investigations revealed that overexpression of ACYP2 inhibited the proliferation and metastasis of HCC cells while promoting apoptosis; knockdown of ACYP2 had the exact opposite effect. Additionally, it was observed that ACYP2 was distributed in both the cytoplasm and nucleus of HCC cells. According to the mechanistic studies, the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) was negatively regulated by cytoplasmic ACYP2, resulting in the inhibition of K+ outflow and subsequent inactivation of the ERK pathway, which impeded the growth and metastasis of HCC. Furthermore, the activity of telomerase reverse transcriptase (TERT) was inhibited by nuclear ACYP2, leading to the reduction in length of telomeres and consequent reversal of HCC cell immortalization. Additionally, a novel targeted nanotherapy strategy was developed wherein the pcDNA-ACYP2 vector was encapsulated within polyetherimide nanoparticles (PEI/NPs), which were subsequently coated with HCC cell membranes (namely pcDNA/PEI/NPs@M). Safety and targeting characteristics abound for these nanocomposites, in both subcutaneous graft tumor models and orthotopic mouse models, they inhibited the progression of HCC by impeding TERT activity and the KCNN4/ERK pathway. In conclusion, our research identifies novel molecular mechanisms involving cytoplasmic and nuclear ACYP2 that inhibit the progression of HCC. Moreover, pcDNA/PEI/NPs@M represents a targeted therapeutic strategy for HCC that holds great promising.

Layer by layer self-assembled hyaluronic acid nanoarmor for the treatment of ulcerative colitis.

Natural compound-based treatments provide innovative ways for ulcerative colitis therapy. However, poor targeting and rapid degradation curtail its application, which needs to be addressed. Inspired by biomacromolecule-based materials, we have developed an orally administrated nanoparticle (GBP@HA NPs) using bovine serum albumin as a carrier for polyphenol delivery. The system synergizes galactosylated bovine serum albumin with two polyphenols, epigallocatechin gallate and tannic acid, which is then encased in "nanoarmor" of ε-Polylysine and hyaluronic acid to boost its stability and targeting. Remarkably, the nanoarmor demonstrated profound therapeutic effects in both acute and chronic mouse models of ulcerative colitis, mitigating disease symptoms via multiple mechanisms, regulating inflammation related factors and exerting a modulatory impact on gut microbiota. Further mechanistic investigations indicate that GBP@HA NPs may act through several pathways, including modulation of Keap1-Nrf2 and NF-κB signaling, as well as Caspase-1-dependent pyroptosis. Consequently, this novel armored nanotherapy promotes the way for enhanced polyphenol utilization in ulcerative colitis treatment research.

Glioblastoma Therapy: Past, Present and Future.

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood-brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer.

The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes.

Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives.

This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, etc.) are outlined. This paper discusses the need to use natural resources for the "green" design of new nanoformulations with therapeutic efficiency. Nanopharmaceuticals research is still in its early stages, and the preparation of nanomaterials must be carefully considered. Therefore, safety and long-term effects of pharmaceutical nanoformulations must not be overlooked. The testing of nanopharmaceuticals represents an essential point in their further applications. Vegetal scaffolds obtained by decellularizing plant leaves represent a valuable, bioinspired model for nanopharmaceutical testing that avoids using animals. Nanoformulations are critical in various fields, especially in pharmacy, medicine, agriculture, and material science, due to their unique properties and advantages over conventional formulations that allows improved solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity. Nanopharmaceuticals have transitioned from experimental stages to being a vital component of clinical practice, significantly improving outcomes in medical fields for cancer treatment, infectious diseases, neurological disorders, personalized medicine, and advanced diagnostics. Here are the key points highlighting their importance. The significant challenges, opportunities, and future directions are mentioned in the final section.

Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and ß subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs.

The Potential of Nuclear Pore Complexes in Cancer Therapy.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosystems in cancer treatment, their role in inhibiting cell invasion is examined. This article concludes with the clinical implications of nuclear export inhibitors, particularly XPO1, as a therapeutic target in various cancers, with selective inhibitors of nuclear export compounds demonstrating efficacy in both hematological and solid malignancies. The review aims to explore the role of NPCs in cancer biology, focusing on their influence on gene expression, cancer progression, protein mislocalization, and the potential of targeted therapies such as nuclear export inhibitors and intelligent nanosystems in cancer treatment. Despite their significance and the number of research studies, the direct role of NPCs in carcinogenesis remains incompletely understood.

Multiple breast cancer liver metastases response to macrophage-delivered nanotherapy evaluated via a 3D continuum model.

Breast cancer liver metastases (BCLM) are usually unresectable and difficult to treat with systemic chemotherapy. A major reason for chemotherapy failure is that BCLM are typically small, avascular nodules, with poor transport and fast washout of therapeutics from surrounding capillaries. We have previously shown that nanoalbumin-bound paclitaxel (nab-PTX) encapsulated in porous silicon multistage nanovectors (MSV) is preferentially taken up by tumour-associated macrophages (TAM) in the BCLM microenvironment. The TAM alter therapeutic transport characteristics and retain it in the tumour vicinity, increasing cytotoxicity. Computational modeling has shown that therapeutic regimens could be designed to eliminate single lesions. To evaluate clinically-relevant scenarios, this study develops a modeling framework to evaluate MSV-nab-PTX therapy targeting multiple BCLM. An experimental model of BCLM, splenic injection of breast cancer 4 T1 cells was established in BALB/C mice. Livers were analyzed histologically to determine size and density of BCLM. The data were used to calibrate a 3D continuum mixture model solved via distributed computing to enable simulation of multiple BCLM. Overall tumour burden was analyzed as a function of metastases number and potential therapeutic regimens. The computational model enables realistic 3D representation of metastatic tumour burden in the liver, with the capability to evaluate BCLM growth and therapy response for hundreds of lesions. With the given parameter set, the model projects that repeated MSV-nab-PTX treatment in intervals <7 days would control the tumour burden. We conclude that nanotherapy targeting TAM associated with BCLM may be evaluated and fine-tuned via 3D computational modeling that realistically simulates multiple metastases.

Self-Therapeutic Nanomaterials: Applications in Biology and Medicine.

Over past decades, nanotechnology has contributed to the biomedical field in areas including detection, diagnosis, and drug delivery via opto-electronic properties or enhancement of biological effects. Though generally considered inert delivery vehicles, a plethora of past and present evidence demonstrates that nanomaterials also exude unique intrinsic biological activity based on composition, shape, and surface functionalization. These intrinsic biological activities, termed self-therapeutic properties, take several forms, including mediation of cell-cell interactions, modulation of interactions between biomolecules, catalytic amplification of biochemical reactions, and alteration of biological signal transduction events. Moreover, study of biomolecule-nanomaterial interactions offers a promising avenue for uncovering the molecular mechanisms of biology and the evolution of disease. In this review, we observe the historical development, synthesis, and characterization of self-therapeutic nanomaterials. Next, we discuss nanomaterial interactions with biological systems, starting with administration and concluding with elimination. Finally, we apply this materials perspective to advances in intrinsic nanotherapies across the biomedical field, from cancer therapy to treatment of microbial infections and tissue regeneration. We conclude with a description of self-therapeutic nanomaterials in clinical trials and share our perspective on the direction of the field in upcoming years.

Natural resources for sustainable synthesis of nanomaterials with anticancer applications: A move toward green nanomedicine.

Today, researchers have focused on the application of environmentally-benign and sustainable micro- and nanosystems for drug delivery and cancer therapy. Compared to conventional chemotherapeutics, advanced micro- and nanosystems designed by applying abundant, natural, and renewable feedstocks have shown biodegradability, biocompatibility, and low toxicity advantages. However, important aspects of toxicological assessments, clinical translational studies, and suitable functionalization/modification still need to be addressed. Herein, the benefits and challenges of green nanomedicine in cancer nanotherapy and targeted drug delivery are cogitated using nanomaterials designed by exploiting natural and renewable resources. The application of nanomaterials accessed from renewable natural resources, comprising metallic nanomaterials, carbon-based nanomaterials, metal-organic frameworks, natural-derived nanomaterials, etc. for targeted anticancer drug delivery and cancer nanotherapy are deliberated, with emphasis on important limitations/challenges and future perspectives.

Recent advances in targeted delivery of non-coding RNA-based therapeutics for atherosclerosis.

Cardiovascular disease (CVD) has overtaken infectious illnesses as the leading cause of mortality and disability worldwide. The pathology that underpins CVD is atherosclerosis, characterized by chronic inflammation caused by the accumulation of plaques in the arteries. As our knowledge about the microenvironment of blood vessel walls deepens, there is an opportunity to fine-tune treatments to target the mechanisms driving atherosclerosis more directly. The application of non-coding RNAs (ncRNAs) as biomarkers or intervention targets is increasing. Although these ncRNAs play an important role in driving atherosclerosis and vascular dysfunction, the cellular and extracellular environments pose a challenge for targeted transmission and therapeutic regulation of ncRNAs. Specificity, delivery, and tolerance have hampered the clinical translation of ncRNA-based therapeutics. Nanomedicine is an emerging field that uses nanotechnology for targeted drug delivery and advanced imaging. Recently, nanoscale carriers have shown promising results and have introduced new possibilities for nucleic acid targeted drug delivery, particularly for atherosclerosis. In this review, we discuss the latest developments in nanoparticles to aid ncRNA-based drug development, particularly miRNA, and we analyze the current challenges in ncRNA targeted delivery. In particular, we highlight the emergence of various kinds of nanotherapeutic approaches based on ncRNAs, which can improve treatment options for atherosclerosis.

Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations.

Atherosclerosis is the main underlying pathology for many cardiovascular diseases (CVDs), which are the leading cause of death globally and represent a serious health crisis. Atherosclerosis is a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease. Elevated plasma lipids, hypertension, and high glucose are the major risk factors for developing atherosclerotic plaques. To date, most pharmacological therapies aim to control these risk factors, but they do not target the plaque-causing cells themselves. In patients with acute coronary syndromes, surgical revascularization with percutaneous coronary intervention has greatly reduced mortality rates. However, stent thrombosis and neo-atherosclerosis have emerged as major safety concerns of drug eluting stents due to delayed re-endothelialization. This review summarizes the major milestones, strengths, and limitations of current anti-atherosclerotic therapies. It provides an overview of the recent discoveries and emerging game-changing technologies in the fields of nanomedicine, mRNA therapeutics, and gene editing that have the potential to revolutionize CVD clinical practice by steering it toward precision medicine.

Targeting integrins for cancer management using nanotherapeutic approaches: Recent advances and challenges.

Integrins are the main cell surface receptors and execute multifaceted functions such as the bidirectional transmission of signals (i.e., inside-out and outside-in) and provide communication between cells and their microenvironments. Integrins are the key regulators of critical biological functions and contribute significantly to the promotion of cancer at almost every stage of disease progression from initial tumor formation to metastasis. Integrin expressions are frequently altered in different cancers, and consequently, several therapeutic strategies targeting integrins have been developed. Furthermore, nanotechnology-based approaches have been devised to overcome the intrinsic limitations of conventional therapies for cancer management, and have been shown to more precise, safer, and highly effective therapeutic tools. Although nanotechnology-based approaches have achieved substantial success for the management of cancer, certain obstacles remain such as inadequate knowledge of nano-bio interactions and the challenges associated with the three stages of clinical trials. This review highlights the different roles of integrins and of integrin-dependent signaling in various cancers and describes the applications of nanotherapeutics targeting integrins. In addition, we discuss RGD-based approaches and challenges posed to cancer management.

Applications and strategies in nanodiagnosis and nanotherapy in lung cancer.

Lung cancer is the second most common cancer and the leading cause of death in both men and women in the world. Lung cancer is heterogeneous in nature and diagnosis is often at an advanced stage as it develops silently in the lung and is frequently associated with high mortality rates. Despite the advances made in understanding the biology of lung cancer, progress in early diagnosis, cancer therapy modalities and considering the mechanisms of drug resistance, the prognosis and outcome still remains low for many patients. Nanotechnology is one of the fastest growing areas of research that can solve many biological problems such as cancer. A growing number of therapies based on using nanoparticles (NPs) have successfully entered the clinic to treat pain, cancer, and infectious diseases. Recent progress in nanotechnology has been encouraging and directed to developing novel nanoparticles that can be one step ahead of the cancer reducing the possibility of multi-drug resistance. Nanomedicine using NPs is continuingly impacting cancer diagnosis and treatment. Chemotherapy is often associated with limited targeting to the tumor, side effects and low solubility that leads to insufficient drug reaching the tumor. Overcoming these drawbacks of chemotherapy by equipping NPs with theranostic capability which is leading to the development of novel strategies. This review provides a synopsis of current progress in theranostic applications for lung cancer diagnosis and therapy using NPs including liposome, polymeric NPs, quantum dots, gold NPs, dendrimers, carbon nanotubes and magnetic NPs.

An Optimally Designed Engineering Exosome-Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing.

Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno-engineered exosome (PCOF@E-Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E-Exo is collected from TNF-α-treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti-inflammatory M2 macrophage polarization, but also stabilizes hypoxia-inducible factor-1α (HIF-1α). More importantly, the PCOF@E-Exo exhibits intriguing bactericide capabilities toward Gram-negative, Gram-positive, and drug-resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.

Recent Advances in Targeted Nanotherapies for Ischemic Stroke.

Ischemic stroke (IS) is a severe neurological disease caused by the narrowing or occlusion of cerebral blood vessels and is known for high morbidity, disability, and mortality rates. Clinically available treatments of stroke include the surgical removal of the thrombus and thrombolysis with tissue fibrinogen activator. Pharmaceuticals targeting IS are uncommon, and the development of new therapies is hindered by the low bioavailability and stability of many drugs. Nanomedicine provides new opportunities for the development of novel neuroprotective and thrombolytic strategies for the diagnosis and treatment of IS. Numerous nanotherapeutics with different physicochemical properties are currently being developed to facilitate drug delivery by accumulation and controlled release and to improve their restorative properties. In this review, we discuss recent developments in IS therapy, including assisted drug delivery and targeting, neuroprotection through regulation of the neuron environment, and sources of endogenous biomimetic specific targeting. In addition, we discuss the role and neurotoxic effects of inorganic metal nanoparticles in IS therapy. This study provides a theoretical basis for the utilization of nano-IS therapies that may contribute to the development of new strategies for a range of embolic diseases.

Research Progress on Nanoplatforms and Nanotherapeutic Strategies in Treating Glioma.

Glioma is the most common and aggressive primary intracranial tumor within the central nervous system. The blood-brain barrier (BBB) has been a great hurdle for an effective glioma treatment. To effectively treat glioma, various strategies have been applied to deliver drugs to the brain by crossing the BBB. Nanocarrier-mediated drug delivery is emerging as an effective and noninvasive system to treat glioma, showing great potential in glioma therapy. In this review, we will provide a comprehensive overview on nanocarrier-mediated drug delivery and related glioma therapy. Following an initial overview of the BBB and blood-brain-tumor barrier (BBTB) structure and characteristics, nanocarrier-mediated drug delivery strategies (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, biomimetic nanoparticles, and exosomes) for crossing the BBB are discussed. Finally, nanotherapeutic techniques (imaging-mediated chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, immunotherapy, ferroptosis therapy, sonodynamic therapy, chemodynamic therapy, and combination therapy) in treating glioma are summarized. In addition, this review provides some perspectives on the clinical applications of nanomedicines.

Self-assembled miRNA-switch nanoparticles target denuded regions and prevent restenosis.

Cardiovascular disease is the leading cause of death and disability worldwide. Effective delivery of cell-selective therapies that target atherosclerotic plaques and neointimal growth while sparing the endothelium remains the Achilles heel of percutaneous interventions. The current study utilizes synthetic microRNA switch therapy that self-assembles to form a compacted, nuclease-resistant nanoparticle <200 nM in size when mixed with cationic amphipathic cell-penetrating peptide (p5RHH). These nanoparticles possess intrinsic endosomolytic activity that requires endosomal acidification. When administered in a femoral artery wire injury mouse model in vivo, the mRNA-p5RHH nanoparticles deliver their payload specifically to the regions of endothelial denudation and not to the lungs, liver, kidney, or spleen. Moreover, repeated administration of nanoparticles containing a microRNA switch, consisting of synthetically modified mRNA encoding for the cyclin-dependent kinase inhibitor p27Kip1 that contains one complementary target sequence of the endothelial cell-specific miR-126 at its 5' UTR, drastically reduced neointima formation after wire injury and allowed for vessel reendothelialization. This cell-selective nanotherapy is a valuable tool that has the potential to advance the fight against neointimal hyperplasia and atherosclerosis.

The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges.

The last decade has witnessed a sustained increase in the research development of modern-day chemo-therapeutics, especially for those used for high mortality rate pathologies. However, the therapeutic landscape is continuously changing as a result of the currently existing toxic side effects induced by a substantial range of drug classes. One growing research direction driven to mitigate such inconveniences has converged towards the study of natural molecules for their promising therapeutic potential. Triterpenes are one such class of compounds, intensively investigated for their therapeutic versatility. Although the pharmacological effects reported for several representatives of this class has come as a well-deserved encouragement, the pharmacokinetic profile of these molecules has turned out to be an unwelcomed disappointment. Nevertheless, the light at the end of the tunnel arrived with the development of nanotechnology, more specifically, the use of liposomes as drug delivery systems. Liposomes are easily synthesizable phospholipid-based vesicles, with highly tunable surfaces, that have the ability to transport both hydrophilic and lipophilic structures ensuring superior drug bioavailability at the action site as well as an increased selectivity. This study aims to report the results related to the development of different types of liposomes, used as targeted vectors for the delivery of various triterpenes of high pharmacological interest.