Brain Targeting Nanomedicines: Pitfalls and Promise.

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.

Enhancing the Inhibition of Breast Cancer Growth Through Synergistic Modulation of the Tumor Microenvironment Using Combined Nano-Delivery Systems.

Purpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells. Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro "condition medium of fibroblasts + MCF-7" cell model and in vivo "4T1/NIH-3T3" co-implantation mice model were established to evaluate the anti-tumor effect of drugs. Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect. Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.

Breaking Barriers: Nanomedicine-Based Drug Delivery for Cataract Treatment.

Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.

Advances in Engineered Nanoparticles for the Treatment of Ischemic Stroke by Enhancing Angiogenesis.

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.

[Atomic Force Microscopy to Measure the Mechanical Property of Nanosized Lipid Vesicles and Its Applications].

Nanoparticles, including liposomes and lipid nanoparticles, have garnered global attention due to their potential applications in pharmaceuticals, vaccines, and gene therapies. These particles enable targeted delivery of new drug modalities such as highly active small molecules and nucleic acids. However, for widespread use of nanoparticle-based formulations, it is crucial to comprehensively analyze their characteristics to ensure both efficacy and safety, as well as enable consistent production. In this context, this review focuses on our research using atomic force microscopy (AFM) to study liposomes and lipid nanoparticles. Our work significantly contributes to the capability of AFM to measure various types of liposomes in an aqueous medium, providing valuable insights into the mechanical properties of these nanoparticles. We discuss the applications of this AFM technique in assessing the quality of nanoparticle-based pharmaceuticals and developing membrane-active peptides.

[Research progress in anti-tumor activity and nano-drug delivery system of piperlongumine].

Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery.

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier - the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment.

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics.

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic cancer with tumor microenvironment-responsive nanoformulation.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-ß/IL-4, -8, -10, and TNF-α/IFN-γ/IL-1, -12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.

Advanced nanoparticle strategies for optimizing RNA therapeutic delivery in neurodegenerative disorders.

Neurodegenerative diseases affect many people worldwide, and as the population ages, the incidence of these conditions increases. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders worldwide. Different medicines are being used to control symptoms related to these conditions, but no treatment has yet been approved. Both genetic and environmental factors are involved in disease pathogenesis, and research on the pathophysiological pathways is still ongoing. The role of subcellular pathways and dysregulation in RNA pathways has been highlighted in pathophysiological studies, and treatment strategies focused on these pathways can be a promising approach. Many experiments have been conducted on delivering RNA cargo to the CNS to modulate various pathways involved. Yet another challenge to be faced is the effective transport of desired molecules to targets, which can be greatly hindered by distinct barriers limiting transport to the CNS, most noticeably the blood-brain barrier (BBB). Nanotechnology and the use of different nano-carriers for the delivery of nucleotides, peptides, proteins, and drug molecules are currently of great interest as these carriers help with better delivery and protection and, as a result, improve the effectiveness of the cargo. Nanocarriers can protect susceptible RNA molecules from possible degradation or destruction and improve their ability to reach the brain by enhancing BBB penetration. Different mechanisms for this process have been hypothesized. This review will go through the therapeutic application of RNA molecules in the treatment of AD and PD and the role of nanocarriers in overcoming delivery challenges and enhancing efficacy.

Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases.

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems have shown promise in solving problems associated with the distribution of hydrophobic drugs and have promoted the accumulation of nanomedicines in the circulation or in organs. However, the injection dose of nanoparticles (NPs) is much greater than that needed by diseased tissues or organs. In other words, most of the NPs are localized off-target and do not reach the desired tissue or organs. With the rapid development of biodegradable and biosafety nanomaterials, the nanovectors represent assurance of safety. However, the off-target effects also induce concerns about the application of NPs, especially in the delivery of gene editing tools. Therefore, a complete understanding of the biological responses to NPs in the body will clearly guide the design of targeted delivery of NPs. The different properties of various nanodelivery systems may induce diverse interactions between carriers and organs. In this review, we describe the relationship between the liver, the most influenced organ of systemic administration of NPs, and targeted delivery nanoplatforms. Various transport vehicles have adopted multiple delivery strategies for the targeted delivery to the cells in the homeostasis liver and in diseased liver. Additionally, nanodelivery systems provide a novel strategy for treating incurable diseases. The appearance of a targeted delivery has profoundly improved the application of NPs to liver diseases.

Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer's disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid ß42 (Aß42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3ß/GSK3ß, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aß42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aß42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Charge-Switchable nanoparticles to enhance tumor penetration and accumulation.

Nanoparticle-based drug delivery systems hold potential in chemotherapy, but their limited accumulation in tumor tissues hinders effective drug concentration for combating tumor growth. Hence, altering the physicochemical properties of nanoparticles, particularly their surface charge, can enhance their performance. This study utilized a computational model to explore a nanoparticle drug delivery system capable of dynamically adjusting its surface charge. In the model, nanoparticles in the bloodstream were assigned a neutral or positive charge, which, upon reaching the tumor microenvironment, switched to a neutral or negative charge, and releasing chemotherapy drugs into the extracellular space. Results revealed that circulating nanoparticles with a positive surface charge, despite having a shorter circulation and high clearance rate compared to their neutral counterparts, could accumulate significantly in the tissue due to their high transvascular rate. After extravasation, neutralized surface-charged nanoparticles tended to accumulate only near blood microvessels due to their low diffusion rate, resulting in substantial released drug drainage back into the bloodstream. On the other hand, nanoparticles with a negative surface charge in the tumor's extracellular space, due to the reduction of nano-bio interactions, were able to penetrate deeper into the tumor, and increasing drug bioavailability by reducing the volume of drained drugs. Furthermore, the analysis suggested that burst drug release yields a higher drug concentration than sustained drug release, however their creation of bioavailability dependent on nanoparticle accumulation in the tissue. The study's findings demonstrate the potential of this delivery system and offer valuable insights for future research in this area.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer.

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke.

In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs).

Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.

Tumor-targeted gypenoside nanodrug delivery system with double protective layers.

OBJECTIVES: Gypenoside (Gyp) is easily degraded in the gastrointestinal tract, resulting in its low bioavailability. We aimed to develop a tumor-targeted Gyp nanodrug delivery system and to investigate its antitumor effect in vitro. MATERIALS AND METHODS: We used Gyp as the therapeutic drug molecule, mesoporous silica (MSN) and liposome (Lipo) as the drug carrier and protective layers, and aptamer SYL3C as the targeting element to establish a tumor-targeted nanodrug delivery system (i.e., SYL3C-Lipo@Gyp-MSN). The characteristics of SYL3C-Lipo@Gyp-MSN were investigated, and its drug release performance, cell uptake, and antitumor activity in vitro were evaluated. RESULTS: A tumor-targeted Gyp nanodrug delivery system was successfully prepared. The SYL3C-Lipo@Gyp-MSN was spherical or ellipsoidal; had good dispersion, which enabled it to specifically target and kill the liver tumor cell HepG2; and effectively protected the early leakage of Gyp. CONCLUSIONS: We have established a tumor-targeted nanodrug delivery system that can target and kill liver cancer cells and may provide a strategy for preparing new nanodrug-loaded preparations of traditional Chinese medicine.