Red Blood Cell-Hitchhiking Delivery of Simvastatin to Relieve Acute Respiratory Distress Syndrome.

Purpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects. Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs). Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug's circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug's efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions. Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM's poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.

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.

Flexible nano-liposomes-based transdermal hydrogel for targeted delivery of dexamethasone for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that can lead to synovitis, cartilage destruction, and even joint damage. Dexamethasone (DEX) is a commonly used agent for RA therapy on inflammation manage. However, the traditional administering DEX is hampered by low efficiency and obvious adverse effects. Therefore, in order to efficiently deliver DEX to RA inflamed joints and overcome existing deficiencies, we developed transdermal formation dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel), validated their transdermal efficiency, evaluated its ability to target activated macrophages, and its anti-inflammatory effect. The DS-FLs/DEX exhibited excellent biocompatibility, sustainable drug release, and high uptake by lipopolysaccharide (LPS)-activated macrophages. Furthermore, the DS-FLs/DEX hydrogel showed desired skin permeation as compared with regular liposome hydrogel (DS-RLs/DEX hydrogel) due to its good deformability. In vivo, when used the AIA rats as RA model, the DS-FLs/DEX hydrogel can effectively penetrate and accumulate in inflamed joints, significantly improve joint swelling in RA rats, and reduce the destructive effect of RA on bone. Importantly, the expression of inflammatory cytokines in joints was inhibited and the system toxicity did not activate under DS-FLs/DEX hydrogel treatment. Overall, these data revealed that the dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel) can prove to be an excellent drug delivery vehicle against RA.

Multi-scale modelling of nanoparticle delivery and heat transport in vascularised tumours.

We focus on modelling of cancer hyperthermia driven by the application of the magnetic field to iron oxide nanoparticles. We assume that the particles are interacting with the tumour environment by extravasating from the vessels into the interstitial space. We start from Darcy's and Stokes' problems in the interstitial and fluid vessels compartments. Advection-diffusion of nanoparticles takes place in both compartments (as well as uptake in the tumour interstitium), and a heat source proportional to the concentration of nanoparticles drives heat diffusion and convection in the system. The system under consideration is intrinsically multi-scale. The distance between adjacent vessels (the micro-scale) is much smaller than the average tumour size (the macro-scale). We then apply the asymptotic homogenisation technique to retain the influence of the micro-structure on the tissue scale distribution of heat and particles. We derive a new system of homogenised partial differential equations (PDEs) describing blood transport, delivery of nanoparticles and heat transport. The new model comprises a double Darcy's law, coupled with two double advection-diffusion-reaction systems of PDEs describing fluid, particles and heat transport and mass, drug and heat exchange. The role of the micro-structure is encoded in the coefficients of the model, which are to be computed solving appropriate periodic problems. We show that the heat distribution is impaired by increasing vessels' tortuosity and that regularization of the micro-vessels can produce a significant increase (1-2 degrees) in the maximum temperature. We quantify the impact of modifying the properties of the magnetic field depending on the vessels' tortuosity.

RNAi-based therapeutics and tumor targeted delivery in cancer.

Over the past decade, non-coding RNA-based therapeutics have proven as a great potential for the development of targeted therapies for cancer and other diseases. The discovery of the critical function of microRNAs (miRNAs) has generated great excitement in developing miRNA-based therapies. The dysregulation of miRNAs contributes to the pathogenesis of various human diseases and cancers by modulating genes that are involved in critical cellular processes, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, drug resistance, and tumorigenesis. miRNA (miRNA mimic, anti-miRNA/antagomir) and small interfering RNA (siRNA) can inhibit the expression of any cancer-related genes/mRNAs with high specificity through RNA interference (RNAi), thus representing a remarkable therapeutic tool for targeted therapies and precision medicine. siRNA and miRNA-based therapies have entered clinical trials and recently three novel siRNA-based therapeutics were approved by the Food and Drug Administration (FDA), indicating the beginning of a new era of targeted therapeutics. The successful clinical applications of miRNA and siRNA therapeutics rely on safe and effective nanodelivery strategies for targeting tumor cells or tumor microenvironment. For this purpose, promising nanodelivery/nanoparticle-based approaches have been developed using a variety of molecules for systemic administration and improved tumor targeted delivery with reduced side effects. In this review, we present an overview of RNAi-based therapeutics, the major pharmaceutical challenges, and the perspectives for the development of promising delivery systems for clinical translation. We also highlight the passive and active tumor targeting nanodelivery strategies and primarily focus on the current applications of nanoparticle-based delivery formulations for tumor targeted RNAi molecules and their recent advances in clinical trials in human cancers.

Overcoming drug delivery barriers and challenges in topical therapy of atopic dermatitis: A nanotechnological perspective.

Atopic dermatitis (AD) is an inflammatory disorder centered around loss of epidermal barrier function, and T helper 2 (Th2) immune responses. The current understanding of disease heterogeneity and complexity, limits the rational use of existing topical, systemic therapeutic agents, but paves way for development of advanced therapeutic agents. Additionally, advanced nanocarriers that deliver therapeutics to target cells, seem to offer a promising strategy, to overcome intrinsic limitations and challenges of conventional, and traditional drug delivery systems. Ever-evolving understanding of molecular target sites and complex pathophysiology, adverse effects of current therapeutic options, inefficient disease recapitulation by existing animal models are some of the challenges that we face. Also, despite limited success in market translatibility, nanocarriers have demonstrated excellent preclinical results and have been extensively studied for AD. Detailed research on behavior of nanocarriers in different patients and tailored therapy to account for phenotypic variability of the disease are the new research avenues that we look forward to.

Drug delivery of 6-bromoindirubin-3'-glycerol-oxime ether employing poly(D,L-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents.

BACKGROUND: Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE. RESULTS: For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around - 15 to - 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen's egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes. CONCLUSIONS: Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential.

Nanomedicine for brain cancer.

CNS tumors remain among the deadliest forms of cancer, resisting conventional and new treatment approaches, with mortality rates staying practically unchanged over the past 30 years. One of the primary hurdles for treating these cancers is delivering drugs to the brain tumor site in therapeutic concentration, evading the blood-brain (tumor) barrier (BBB/BBTB). Supramolecular nanomedicines (NMs) are increasingly demonstrating noteworthy prospects for addressing these challenges utilizing their unique characteristics, such as improving the bioavailability of the payloadsviacontrolled pharmacokinetics and pharmacodynamics, BBB/BBTB crossing functions, superior distribution in the brain tumor site, and tumor-specific drug activation profiles. Here, we review NM-based brain tumor targeting approaches to demonstrate their applicability and translation potential from different perspectives. To this end, we provide a general overview of brain tumor and their treatments, the incidence of the BBB and BBTB, and their role on NM targeting, as well as the potential of NMs for promoting superior therapeutic effects. Additionally, we discuss critical issues of NMs and their clinical trials, aiming to bolster the potential clinical applications of NMs in treating these life-threatening diseases.

Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors.

BACKGROUND: Malignant tumor is usually associated with epigenetic dysregulation, such as overexpression of histone deacetylase (HDAC), thus HDAC has emerged as a therapeutic target for cancer. Histone deacetylase inhibitor has been approved for clinical use to treat hematological cancers. However, the low solubility, short circulation lifetime, and high cytotoxicity partially limited their applications in solid tumor. METHODS: The upconversion nanoparticles (UC) modified with mesoporous silica (SUC) was used to load an HDACI, suberoylanilide hydroxamic acid (SAHA), and further camouflaged with M1 macrophage-derived exosome membranes (EMS). EMS was characterized in size and compositions. We also analyzed the epigenetic regulation induced by EMS. Furthermore, we evaluate the biodistribution and in vivo tumor inhibition after the systemic administration of EMS. RESULTS: This novel style spatiotemporal-resolved drug delivery system, EMS showed a high loading efficiency of SAHA. EMS could be taken up by lung cancer cells and lead to efficient epigenetic inhibition. We found that the integrin α4ß1 on M1-EM, was crucial for the homing of EMS to tumor tissues for the first time. In tumor-bearing mice, EMS showed spatiotemporal-resolved properties and facilitated the drug accumulation in the tumors, which induced superior anti-tumor effects. CONCLUSION: This novel style of spatiotemporal-resolved nanoparticles can be used as a theranostic platform for lung cancer therapy.

Nanomedicine from amphiphilizedprodrugs: Concept and clinical translation.

Nanomedicines generally consisting of carrier materials with small fractions of active pharmaceutical ingredients (API) have long been used to improve the pharmacokinetics and biodistributions, augment the therapeutic efficacies and mitigate the side effects. Amphiphilizing hydrophobic/hydrophilic drugs to prodrugs capable of self-assembly into well-defined nanostructures has emerged as a facile approach to fabricating nanomedicines because this amphiphilized prodrug (APD) strategy presents many advantages, including minimized use of inert carrier materials, well-characterized prodrug structures, fixed and high drug loading contents, 100% loading efficiency, and burst-free but controlled drug release. This review comprehensively summarizes recent advances in APDs and their nanomedicines, from the rationale and the stimuli-responsive linker chemistry for on-demand drug release to their progress to the clinics, clinical performance of APDs, as well as the challenges and perspective on future development.

HPLC with fluorescence detection for the bioanalysis and pharmacokinetic study of Doxorubicin and Prodigiosin loaded on eco-friendly casein nanomicelles in rat plasma.

A rapid, efficient, and sensitive liquid chromatographic assay hyphenated to fluorometric detector (HPLC-FLD) was developed and validated for the determination of doxorubicin (DXR) and prodigiosin (PDG) in rat plasma. The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency (98% and 85% for DXR and PDG, respectively). The chromatographic separation was accomplished using stationary phase: Agilent Zorbax Eclipse plus-C18 analytical column (250 × 4.6 mm, 5 µm) and gradient eluting mobile phase of ammonium acetate (pH = 3), acetonitrile and methanol with programmed fluorescence detection. As the proposed method has been validated, it was subsequently implemented to evaluate DXR and PDG loaded on novel eco-friendly Casein nano drug delivery system after intravenous injection in healthy rats. A comparative pharmacokinetics' study was carried out in rats for DXR in free form, DXR alone entrapped in the nanomicelle and DXR with PDG entrapped in the nano micelle. After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters. This indicates that the presented nanomicelle delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe, and potent formulation. This novel nanomicelle has negligible effect on the distribution and elimination of DXR.

Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. RESULTS: Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. CONCLUSION: This strategy may provide a practical approach for targeted therapy of ESCC.

Tumor microenvironment-responsive dynamic inorganic nanoassemblies for cancer imaging and treatment.

Dynamic inorganic nanoassemblies (DINAs) have emerged as smart nanomedicine platforms with promising potential for bioimaging and targeted drug delivery. In this review, we keep abreast of the advances in development of tumor microenvironment (TME)-responsive DINAs to meet the challenges associated with precise cancer therapy. TME-responsive DINAs are designed to achieve precise switches of structures/functions in response to TME-specific stimuli including reactive oxygen species (ROS), reduced pH and hypoxia, so as to enhance the tumor accumulation of nanoassemblies, overcome the biological barriers during intratumoral penentration of therapeutics, and achieve tumor-specific imaging and therapy. This progress report will summarize various types of recently reported smart DINAs for TME-responsive tumor imaging and therapy. Their future development towards potential clinical translation will also be discussed.

Oral nanomedicine for modulating immunity, intestinal barrier functions, and gut microbiome.

The gastrointestinal tract (GIT) affects not only local diseases in the GIT but also various systemic diseases. Factors that can affect the health and disease of both GIT and the human body include 1) the mucosal immune system composed of the gut-associated lymphoid tissues and the lamina propria, 2) the intestinal barrier composed of mucus and intestinal epithelium, and 3) the gut microbiota. Selective delivery of drugs, including antigens, immune-modulators, intestinal barrier enhancers, and gut-microbiome manipulators, has shown promising results for oral vaccines, immune tolerance, treatment of inflammatory bowel diseases, and other systemic diseases, including cancer. However, physicochemical and biological barriers of the GIT present significant challenges for successful translation. With the advances of novel nanomaterials, oral nanomedicine has emerged as an attractive option to not only overcome these barriers but also to selectively deliver drugs to the target sites in GIT. In this review, we discuss the GIT factors and physicochemical and biological barriers in the GIT. Furthermore, we present the recent progress of oral nanomedicine for oral vaccines, immune tolerance, and anti-inflammation therapies. We also discuss recent advances in oral nanomedicine designed to fortify the intestinal barrier functions and modulate the gut microbiota and microbial metabolites. Finally, we opine about the future directions of oral nano-immunotherapy.

Nanoparticle designs for delivery of nucleic acid therapeutics as brain cancer therapies.

Glioblastoma (GBM) is an aggressive central nervous system cancer with a dismal prognosis. The standard of care involves surgical resection followed by radiotherapy and chemotherapy, but five-year survival is only 5.6% despite these measures. Novel therapeutic approaches, such as immunotherapies, targeted therapies, and gene therapies, have been explored to attempt to extend survival for patients. Nanoparticles have been receiving increasing attention as promising vehicles for non-viral nucleic acid delivery in the context of GBM, though delivery is often limited by low blood-brain barrier permeability, particle instability, and low trafficking to target brain structures and cells. In this review, nanoparticle design considerations and new advances to overcome nucleic acid delivery challenges to treat brain cancer are summarized and discussed.

A review on albumin as a biomaterial for ocular drug delivery.

Development of ocular drug delivery system is one of the most technically challenging tasks, when compared with other routes of drug delivery. Eye (an intricate organ) is highly sophisticated and sensitive organ due to presence of various structurally differed anatomical layers, which many times limits the drug delivery approaches. Despite several limitations, many advancements have been made as evidence from various recent studies involving improvement of both residence time and permeation of the drug at the ocular region. In the last few decades, albumin(s) based ophthalmic products have been gained most attention to solve the major challenges associated with conventional ocular drug delivery systems. Interestingly, an albumin-based micro, nano, conjugates, and genetically fused target specific to ligand(s) formulation being exploited through many studies for successful ocular delivery of bioactives (mostly repurposed drugs). Past and current studies suggested that albumin(s) based ocular drug delivery system is multifunctional in nature and capable of extending both drug residence time and sustaining the release of drugs to deliver desired pharmacological outcomes. Despite wide applications, still complete progress made in albumin based ocular drug delivery is limited in literature and missing in market. So, herein we presented an overview to explore the key concepts of albumin-based nanocarrier(s) including strategies involved in the treatment of ocular disease, that have yet to be explored.

Comparative Evaluation for Controlled Release of Amoxicillin from RSM-CCD-Optimized Nanocomposites Based on Sodium Alginate and Chitosan-Containing Inclusion Complexes.

Amoxicillin (AMX) is a semisynthetic antibiotic, an analogue of ampicillin, with a wide spectrum of bacterial activity against many microorganisms but possesses some limits. To increase the drug effectiveness, supramolecule nanocomposites composed of ß-cyclodextrin (ß-CD) and chitosan/sodium alginate/GO were chosen in the present study as a sustained release formulation. Nanocomposites of chitosan (CH), sodium alginate (ALG), and graphene oxide (GO) were synthesized at 50 °C. The inclusion complexes (ICs) were processed via the physical mixture (PM), kneading (KM), microwave (MW) method, or coprecipitation (CP) and directly loaded into the nanocomposite. To confirm the formation of true ICs, the ICs were analyzed by DSC, SEM, 1H NMR, 2D NMR ROESY, and XRD. A drug release study was performed to find out which method is best for the controlled release of drugs in different environments of pH 2, 7, and 7.4 at 37 °C. From the observed drug release data, it was found that PM and KM showed a burst release of drugs and the microwave method was the most suitable method to prepare exact ICs of AMX and ß-CD for sustained release of drugs. Kinetics of drug release was analyzed by various kinetic models, and it was observed that the Korsmeyer-Peppas and Peppas-Sahlin models were best fit for drug release in all cases. A Phase solubility study was carried out to find the stoichiometry of IC formation and the complexation constant. The drug release was controlled and pH-dependent, confirming that nanocomposites are pH-sensitive. From drug release analysis, it was acknowledged that ß-CD is capable of causing sustained drug release.

Tumor-targeted hyaluronic acid-mPEG modified nanostructured lipid carriers for cantharidin delivery: An in vivo and in vitro study.

AIM: Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial. METHODS: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm. RESULTS: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%. CONCLUSIONS: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.

Establishment and characterization of lung co-culture spheroids for paclitaxel loaded Eudragit® RL 100 nanoparticle evaluation.

3D cell cultures are regarded as a better and more relevant approach for screening drugs and therapeutics, particularly due to their likeness with the in vivo conditions. Spheroids offer an intermediate platform between in vitro and in vivo models, for conducting tumor-based investigations. In this study, a simple setup was developed for consistent generation of lung co-culture spheroids, which were developed using the cancer cell lines A549, NCI H460, and fibroblast cells WI-38. The potential of these spheroids for evaluating the toxicity of Eudragit® RL 100 nanoparticles (ENP) was explored. Monodisperse ENP, having the size range of 140-200 nm was prepared using the nanoprecipitation method. These were loaded with the poorly water-soluble anticancer drug paclitaxel. The evaluation of toxicity and uptake of drug-loaded ENP revealed that 2D monolayers were more sensitive to treatment than 3D spheroids. Within spheroids, co-cultures were more resistant to the treatment than monocultures. Overall, our findings demonstrated that the lung co-culture spheroids were a suitable model for accelerating the efficacy and toxicity-related investigations of novel drug delivery systems.

Combating liver cancer through GO-targeted biomaterials.

Hydroxycamptothecin (HCPT) is a topoisomerase I inhibitor, and it has been widely used clinically in the treatment of primary liver cancer, gastric cancer, and other tumors. The clinical application of HCPT is limited by its water solubility, and it has certain toxicity to patients with tumor. Therefore, the effective tumor site accumulation of HCPT is necessary. This work studied the inhibitory effect of HCPT on the proliferation and migration of human liver cancer cells (HepG-2) and used carboxymethyl chitosan (CMC) and hyaluronic acid (HA) to modify graphene oxide (GO) as nano-carrier materials, which load HCPT to achieve a drug delivery system for liver tumors with good biocompatibility and high drug loading. HCPT can significantly inhibit proliferation and migration of HepG-2, enhance the release of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The GO-CMC-HA/HCPT drug delivery system enabled HepG-2 to uptake more HCPT, thereby inhibiting its proliferation and improving the efficacy of HCPTin vivoandin vitro. This study explored a potential therapy strategy by preparing a GO-based tumor-targeted drug delivery system.