Engineered inulin-based hybrid biomaterials for augmented immunomodulatory responses.

Modified biopolymers that are based on prebiotics have been found to significantly contribute to immunomodulatory events. In recent years, there has been a growing use of modified biomaterials and polymer-functionalized nanomaterials in the treatment of various tumors by activating immune cells. However, the effectiveness of immune cells against tumors is hindered by several biological barriers, which highlights the importance of harnessing prebiotic-based biopolymers to enhance host defenses against cancer, thus advancing cancer prevention strategies. Inulin, in particular, plays a crucial role in activating immune cells and promoting the secretion of cytokines. Therefore, this mini-review aims to emphasize the importance of inulin in immunomodulatory responses, the development of inulin-based hybrid biopolymers, and the role of inulin in enhancing immunity and modifying cell surfaces. Furthermore, we discuss the various approaches of chemical modification for inulin and their potential use in cancer treatment, particularly in the field of cancer immunotherapy.

Optimized Design of Hyaluronic Acid-Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells.

Triple-negative breast cancer (TNBC) presents treatment challenges due to a lack of detectable surface receptors. Natural killer (NK) cell-based adaptive immunotherapy is a promising treatment because of the characteristic anticancer effects of killing malignant cells directly by secreting cytokines and lytic granules. To maximize the cancer recognition ability of NK cells, biomaterial-mediated ex vivo cell surface engineering has been developed for sufficient cell membrane immobilization of tumor-targeting ligands via hydrophobic anchoring. In this study, we optimized amphiphilic balances of NK cell coating materials composed of CD44-targeting hyaluronic acid (HA)-poly(ethylene glycol) (PEG)-lipid to improve TNBC recognition and the anticancer effect. Changes in the modular design of our material by differentiating hydrophilic PEG length and incorporating lipid amount into HA backbones precisely regulated the amphiphilic nature of HA-PEG-lipid conjugates. The optimized biomaterial demonstrated improved anchoring into NK cell membranes and facilitating the surface presentation level of HA onto NK cell surfaces. This led to enhanced cancer targeting via increasing the formation of immune synapse, thereby augmenting the anticancer capability of NK cells specifically toward CD44-positive TNBC cells. Our approach addresses targeting ability of NK cell to solid tumors with a deficiency of surface tumor-specific antigens while offering a valuable material design strategy using amphiphilic balance in immune cell surface engineering techniques.

Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming.

Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.

Design of manganese-based nanomaterials for pharmaceutical and biomedical applications.

In the past few years, manganese-based nanostructures have been extensively investigated in the biomedical field particularly to design highly biocompatible theranostics, which can not only act as efficient diagnostic imaging contrast agents but also deliver the drugs to the target sites. The nanoscale size, large surface area-to-volume ratio, availability of cheap precursors, flexibility to synthesize nanostructures with reproducible properties and high yield, and easy scale up are the major reasons for the attraction towards manganese nanostructures. Along with these properties, the nontoxic nature, pH-sensitive degradation, and easy surface functionalization are additional benefits for the use of manganese nanostructures in biomedical and pharmaceutical sciences. Therefore, in this review, we discuss the recent progress made in the synthesis of manganese nanostructures, describe the attempts made to modify their surfaces to impart biocompatibility and stability in biological fluids, and critically discuss their use in magnetic resonance imaging, drug and gene delivery, hyperthermia, photothermal/photodynamic, immunotherapy, biosensing and tumor diagnosis.

Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy.

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.

Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting.

Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acid-overexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module. Therefore, a 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-conjugated di-PEG-PBA (DSPEPEG-di(PEG-PBA) biomaterial was synthesized. The DSPEPEG-di(PEG-PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6.5 and 7.4. DSPEPEG-di(PEG-PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells. Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.

Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma.

Natural killer (NK) cells exhibit a good therapeutic efficacy against various malignant cancer cells. However, the therapeutic efficacy of plain NK cells is relatively low due to inadequate selectivity for cancer cells. Therefore, to enhance the targeting selectivity and anticancer efficacy of NK cells, we have rationally designed a biomaterial-mediated ex vivo surface engineering technique for the membrane decoration of cancer recognition ligands onto NK cells. Our designed lipid conjugate biomaterial contains three major functional moieties: (1) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid for cell membrane anchoring, (2) polyethylene glycol for intracellular penetration blocker, and (3) lactobionic acid (LBA) for cancer recognition. The biomaterial was successfully applied to NK cell surfaces (LBA-NK) to enhance recognition and anticancer functionalities, especially toward asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma. Highly efficient and homogeneous NK cell surface editing was achieved with a simple coating process while maintaining intrinsic properties of NK cells. LBA-NK cells showed potential ASGPR-mediated tumor cell binding (through LBA-ASGPR interaction) and thereby significantly augmented anticancer efficacies against HepG2 liver cancer cells. Thus, LBA-NK cells can be a novel engineering strategy for the treatment of liver cancers via facilitated immune synapse interactions in comparison with currently available cell therapies.

Polymeric biomaterial-inspired cell surface modulation for the development of novel anticancer therapeutics.

Immune cell-based therapies are a rapidly emerging class of new medicines that directly treat and prevent targeted cancer. However multiple biological barriers impede the activity of live immune cells, and therefore necessitate the use of surface-modified immune cells for cancer prevention. Synthetic and/or natural biomaterials represent the leading approach for immune cell surface modulation. Different types of biomaterials can be applied to cell surface membranes through hydrophobic insertion, layer-by-layer attachment, and covalent conjugations to acquire surface modification in mammalian cells. These biomaterials generate reciprocity to enable cell-cell interactions. In this review, we highlight the different biomaterials (lipidic and polymeric)-based advanced applications for cell-surface modulation, a few cell recognition moieties, and how their interplay in cell-cell interaction. We discuss the cancer-killing efficacy of NK cells, followed by their surface engineering for cancer treatment. Ultimately, this review connects biomaterials and biologically active NK cells that play key roles in cancer immunotherapy applications.

Folate Functionalized and Evodiamine-Loaded Pluronic Nanomicelles for Augmented Cervical Cancer Cell Killing.

Evodiamine (Evo) is a natural, biologically active plant alkaloid with wide range of pharmacological activities. In the present study Evo-loaded folate-conjugated Pluronic F108 nano-micelles (ENM) is synthesized to enhance the therapeutic efficacy of Evo against cervical cancer. ENM are synthesized, physicochemically characterized and in vitro anticancer activity is performed. The study demonstrates that ENM have nanoscale size (50.33 ± 3.09 nm), monodispersity of 0.122 ± 0.072, with high drug encapsulation efficiency (71.30 ± 3.76%) and controlled drug release at the tumor microenvironment. ENM showed dose-dependent and time-dependent cytotoxicity against HeLa human cervical cancer cells. The results of in vitro anticancer studies demonstrated that ENM have significant anticancer effects and greatly induce apoptosis as compared to pure Evo. The cellular uptake study suggests that increased anticancer activity of ENM is due to the improved intracellular delivery of Evo through overexpressed folate receptors. Overall, the designed ENM can be a potential targeted delivery system for hydrophobic anticancer bioactive compound like Evo.

Matrix metalloproteinase enzyme responsive delivery of 5-Fluorouracil using Collagen-I peptide functionalized Dendrimer-Gold nanocarrier.

OBJECTIVE: The aim was to develop matrix metalloproteinase 1 (MMP1) responsive nanoparticle system for the delivery of 5-fluorouracil (5Fu) anticancer drug. SIGNIFICANCE: The MMP1 in the cancer microenvironment-induced drug release have the advantage of targeted drug release and reduce the distribution of drug to the healthy tissues. METHOD: G5 poly(amidoamine) (PAMAM) dendrimer (G5)-coated gold nanoparticles (G5AuNP) were synthesized and loaded with 5Fu. The drug-loaded nanoparticles were further coated with collagen I (Col-I) peptide, which is a substrate for MMP1 enzyme (Col-I 5Fu@G5AuNP). RESULT: The nanoparticles were highly monodispersed with a particle size of 30 nm and showed high drug encapsulation efficiency. The release of drug from the nanoparticles in HEPES buffer pH 7.4 was faster, higher and better controlled when incubated with MMP1 enzyme. The half-maximum inhibitory concentration for Col-I 5Fu@G5AuNP was eight times lower than the 5Fu against MCF-7, suggesting the improved delivery and anticancer activity of 5Fu after encapsulation in the developed enzyme-responsive nanocarrier system. The computed tomography (CT) X-ray attenuation of Col-I@G5AuNP showed a good contrasting property. CONCLUSION: The formulation Col-I 5Fu@G5AuNP has improved anticancer activity than free drug and the CT imaging results are promising for its theranostic applications for breast cancer treatment.

Improving Anticancer Activity of Chrysin using Tumor Microenvironment pH-Responsive and Self-Assembled Nanoparticles.

Chrysin is a natural bioactive compound with potential biological activities. However, unfavorable physicochemical properties of native chrysin make it difficult to achieve good therapeutic efficacies. In this study, poly(ethylene) glycol (PEG4000)-conjugated chrysin nanoparticles were prepared. The PEG4000 was conjugated to chrysin through cis-aconityl and succinoyl linkers to achieve tumor microenvironment-specific drug release from PEGylated nanoparticles. The conjugation of PEG and chrysin via succinoyl (PCNP-1) and cis-aconityl (PCNP-2) linkers was confirmed by the 1H NMR and FTIR analysis. The nanoparticles were characterized by DLS, TEM, XRD, and DSC analysis. Comparatively, PCNP-2 showed a better drug release profile and higher anticancer activity against human breast cancer cells than chrysin or PCNP-1. The apoptosis studies and colony formation inhibition assay revealed that the PCNP-2 induced more apoptosis and more greatly controlled the growth of human breast cancer cells than pure chrysin. Thus, the use of PCNPs may help to overcome the issues of chrysin and could be a better therapeutic approach.

Genistein encapsulated inulin-stearic acid bioconjugate nanoparticles: Formulation development, characterization and anticancer activity.

Achieving controlled and site-specific delivery of hydrophobic drugs in the colon environment is a major challenge. The primary goal of this research was to synthesize inulin-stearic acid (INU-SA) conjugate and to evaluate its potential in the site-specific delivery of genistein (GEN) for the treatment of colon cancer. INU is a hydrophilic polysaccharide biological macromolecule was modified with hydrophobic SA to form amphiphilic conjugate (INU-SA) which can self-assemble into spherical nanoparticles with interesting drug release properties. The hydrophobic GEN was encapsulated into the INU-SA conjugate to prepare GEN loaded nanoparticles (GNP). The prepared GNP possessed nano size (115 nm), good colloidal dispersibility (0.066 PDI), and high drug encapsulation efficiency (92.2%). The release behaviour of GNP indicated the site-specific release of GEN, only 3.4% at gastric pH while 94% at intestinal pH. The prepared GNP showed potential cytotoxicity against HCT 116 human colorectal cancer cells, as demonstrated by antiproliferation and apoptosis assays. The observed half maximum inhibitory concentration (IC50) value of GNP (5.5 µg/mL) was significantly lower than pure GEN (28.2 µg/mL) due to higher cellular internalization of GNP than free GEN. Therefore, this research suggests a way to improve the therapeutic effectiveness of natural biomolecules using modified and biocompatible polysaccharide INU.

Inulin coated Mn3O4 nanocuboids coupled with RNA interference reverse intestinal tumorigenesis in Apc knockout murine colon cancer models.

This study reports the development and pre-clinical evaluation of biodrug using RNA interference and nanotechnology. The major challenges in achieving targeted gene silencing in vivo include the stability of RNA molecules, accumulation into pharmacological levels, and site-specific targeting of the tumor. We report the use of Inulin for coating the arginine stabilized manganese oxide nanocuboids (MNCs) for oral delivery of shRNA to the gut. Furthermore, bio-distribution analysis exhibited site-specific targeting in the intestines, improved pharmacokinetic properties, and faster elimination from the system without cytotoxicity. To evaluate the therapeutic possibility and effectiveness of this multimodal bio-drug, it was orally delivered to Apc knockout colon cancer mice models. Persistent and efficient delivery of bio-drug was demonstrated by the knockdown of target genes and increased median survival in the treated cohorts. This promising utility of RNAi-Nanotechnology approach advocates the use of bio-drug in an effort to replace chemo-drugs as the future of cancer therapeutics.

Biotinylated Mn3O4 nanocuboids for targeted delivery of gemcitabine hydrochloride to breast cancer and MRI applications.

Multifunctional nanocarriers have been found as potential candidate for the targeted drug delivery and imaging applications. Herein, we have developed a biocompatible and pH-responsive manganese oxide nanocuboid system, surface modified with poly (ethylene glycol) bis(amine) and functionalized with biotin (Biotin-PEG-MNCs), for an efficient and targeted delivery of an anticancer drug (gemcitabine, GEM) to the human breast cancer cells. GEM-loaded Biotin-PEG@MNCs showed high drug loading efficiency, controlled release of GEM and excellent storage stability in the physiological buffers and different temperature conditions. GEM-loaded Biotin-PEG@MNCs showed dose- and time-dependent decrease in the viability of human breast cancer cells. Further, it exhibited significantly higher cell growth inhibition than pure GEM which suggested that Biotin-PEG@MNCs has efficiently delivered the GEM into cancerous cells. The role of biotin in the uptake was proved by the competitive binding-based cellular uptake study. A significant decrease in the amount of manganese was observed in biotin pre-treated cancer cells as compared to biotin untreated cancer cells. In MRI studies, Biotin-PEG-MNCs showed both longitudinal and transverse relaxivity about 0.091 and 7.66 mM-1 s-1 at 3.0 T MRI scanner, respectively. Overall, the developed Biotin-PEG-MNCs presents a significant potential in formulation development for cancer treatment via targeted drug delivery and enhanced MRI contrast imaging properties.

Self-assembled and pH-responsive polymeric nanomicelles impart effective delivery of paclitaxel to cancer cells.

Chemotherapy is an essential component of breast cancer therapy, but it is associated with serious side effects. Herein, a pluronic F68-based pH-responsive, and self-assembled nanomicelle system was designed to improve the delivery of paclitaxel (PTX) to breast cancer cells. Two pH-responsive pluronic F68-PTX conjugates i.e. succinoyl-linked conjugate (F68-SA-PTX) and cis-aconityl-linked conjugate (F68-CAA-PTX) were designed to respond the varying pH-environment in tumour tissue. Although both the linkers showed pH-sensitivity, the F68-CAA-PTX exhibited superior pH-sensitivity over the F68-SA-PTX and achieved a more selective release of PTX from the self-assembled nanomicelles. The prepared nanomicelles were characterized by dynamic light scattering, transmittance electron microscopy, differential scanning calorimetry and powder X-ray diffraction techniques. The anticancer activity of prepared nanomicelles and pure PTX were evaluated by 2D cytotoxicity assay against breast cancer cell line MDA-MB-231 and in the real tumour environments i.e. 3D tumor spheroids of MDA-MB-231 cells. The highest cytotoxicity effect of PTX was observed with F68-CAA-PTX nanomicelles followed by F68-SA-PTX and free PTX. Further, the F68-CAA-PTX nanomicelles also induced significant apoptosis with a combination of increase in ROS generation, decrease in the depolarisation of MMP and G2/M cell cycle arrest. These observed results provide a new insight for breast cancer treatment using pluronic nanomicelles.

Baicalin encapsulating lipid-surfactant conjugate based nanomicelles: Preparation, characterization and anticancer activity.

Lung cancer is one of the most common malignant tumors and emerged as one of the leading causes of cancer-related death worldwide. Surgical resection can be a curative treatment for early stage but the most of lung cancer patients are diagnosed at an advanced stage when the pulmonary tumor has been invaded beyond the respiratory system. Therefore, chemotherapy is suitable for curing metastasized tumor. Baicalin (BL) is a flavonoid which has been studied in the treatment of several types of cancer including lung cancer. However, its low solubility in water and non-specificity impede its practical utilization. Hence, we have reported a stearic acid and pluronic F68 conjugated nanomicelles (PF68-SA) system to improve therapeutic efficacy of BL. Solvent evaporation method was used to prepare the BL-loaded PF68-SA nanomicelles (BLNM). The designed BLNM were characterized for the particle size, surface charge, critical micelle concentration, colloidal stability, morphology, and total drug content. BLNM formulation showed improved toxicity of BL against A549 human lung cancer cells in cytotoxicity assay. Further, apoptosis study also depicted BLNM-induced cell death in A549 cells. Therefore, the synthesized fatty acid-modified polymeric nanomicellar system could be useful in overcoming the stability and low therapeutic efficacy issues of hydrophobic anticancer drugs like BL and delivering them to the cancer cells.

Inulin-pluronic-stearic acid based double folded nanomicelles for pH-responsive delivery of resveratrol.

Herein, we introduce a novel amphiphilic bioconjugate (INU-F68-SA), synthesized by functionalization of pluronic F68 with a polysaccharide inulin (INU) and a lipid stearic acid (SA). The synthesis of INU-F68-SA was confirmed by FTIR and 1H-NMR analysis. INU-F68-SA can self-assemble into nanomicelles and therefore, its application in delivering of hydrophobic resveratrol (RSV) was investigated. The RSV-loaded INU-F68-SA nanomicelles (RSNM) had about 172 nm size, spherical shape, 0.237 polydispersity index, and -18 mV zeta potential. More importantly, the RSNM showed high drug entrapment efficiency, controlled drug release and protection of drug during storage. The RSNM significantly enhanced the cytotoxicity of RSV against colorectal cancer cells by inducing apoptosis and changing mitochondrial membrane potential. Further, in-vivo pharmacokinetic experiment indicated an improvement in pharmacokinetics of RSV after administering as RSNM. Thus, the use of self-assembled nanomicelles of amphiphilic INU-F68-SA bioconjugate could be a better alternative to overcome the poor in-vitro and in-vivo performance of RSV.

Site-specific delivery of a natural chemotherapeutic agent to human lung cancer cells using biotinylated 2D rGO nanocarriers.

Chemotherapy has remained one of the most commonly employed treatment modalities for cancer. Despite the clinical availability of a large number of chemotherapeutic agents, the uncontrolled systemic distribution and the associated harmful side effects of chemotherapeutic agents pose major challenges demanding concerted efforts to enhance their cancer targetability. The layered structure of two-dimensional (2D) materials offers new opportunities by increasing the drug pay-load influencing the drug-release kinetics in a cancer micro-environment and facilitating targetability through the large accessible surface area. To investigate such potential benefits of 2D materials, we have developed a biocompatible targeted 2D drug delivery system using graphene oxide (GO) as a model nanocarrier (NC) that could hold a high concentration of gallic acid (GA), a natural chemotherapeutic agent found in green tea. Interestingly, the antioxidant nature of GA also reduced GO to a high-quality few-layered thin reduced-graphene oxide (rGO) during drug loading while forming rGO nanocarrier (rGONC). The biotinylated rGONC further improved their targetability to A549 human lung carcinoma cells and they enhanced cellular internalization efficiency. From these targeted 2D NCs, the drug could release only slowly at the physiological pH but liberated rapidly at lower pH encountered by the tumor microenvironment resulting in significant toxicity toward the lung carcinoma cells. As such, this work opens up new possibilities for employing 2D materials for targeted chemotherapeutic applications.

Amorphous nano morin outperforms native molecule in anticancer activity and oral bioavailability.

In the past decade, naturally occurring phytoconstituents have emerged as potential therapeutic agents and alternative to synthetic drugs. However, efficient delivery of hydrophobic phytoconstituents into the body with desired therapeutic efficacy is a key challenge for the pharmaceutical industries due to their insolubility in water and low oral bioavailability. Nanosuspension formulations have shown promises to improve the delivery of the hydrophobic molecules with simultaneously avoiding the drawbacks like carrier toxicity and scale-up issues of other nanotechnology-based drug delivery systems. In this study, we have used morin hydrate (MH), a flavonol, and developed MH nanosuspension formulation (MHNS) to improve its poor physiochemical properties and low oral bioavailability. Different stabilizers with varying concentrations were investigated for preparing nanosuspension. MHNS was characterized by DLS, TEM, FTIR, DSC, powder XRD and was evaluated for its solubility, dissolution, partition coefficient, in-vitro anticancer activity and pharmacokinetics in rats. The optimized nanosuspension formulation, with a size of <100 nm, is capable of increasing aqueous solubility, dissolution rate, and oral bioavailability of MH. Moreover, the therapeutic efficacy, in terms of cytotoxicity to human lung cancer cells, of MH was also increased after formulating into nanosuspension form.