Liquid Crystal Nanoparticles Research Articles

Lyotropic liquid crystals for parenteral drug delivery

The necessity for long-term treatments of chronic diseases has encouraged the development of novel long-acting parenteral formulations intending to improve drug pharmacokinetics and therapeutic efficacy. Lately, one of the novel approaches has been developed based on lipid-based liquid crystals. The lyotropic liquid crystal (LLC) systems consist of amphiphilic molecules and are formed in presence of solvents with the most common types being cubic, hexagonal and lamellar mesophases. LC injectables have been recently developed based on polar lipids that spontaneously form liquid crystal nanoparticles in aqueous tissue environments to create the in-situ long-acting sustained-release depot to provide treatment efficacy over extended periods. In this manuscript, we have consolidated and summarized the various type of liquid crystals, recent formulation advancements, analytical evaluation, and therapeutic application of lyotropic liquid crystals in the field of parenteral sustained release drug delivery.

Application of TiO2 nanoparticle and polyimide blend alignment layer in liquid crystal lens

Suspension of colloidal nanoparticles (NPs) in liquid crystals (LCs) is a common technology to modify the electro-optical characteristics of a LC device. Unfortunately, NP aggregation spontaneously proceeds over time through the dipolar attractive interaction between NPs and results in the light scattering and distortion of the nematic order, which degrades the performance of the LC device. Here, rutile titanium dioxide (TiO2) NPs were suspended in the alignment layer rather than LCs to prevent the proceeding NP aggregation. During the deposition of the alignment layer, the NPs were hardened in the alignment layer with a hard bake process. The blend alignment layer was utilized to develop a hole-patterned liquid crystal (HLC) lens. This layer enhances the polar anchoring of LCs because of the intermolecular interaction between NP and LC and reduces the ion density and rotational viscosity of the LC mixture through harvested effect of free-ions. It also assists in spreading the fringing electric field toward lens center by TiO2 NP contribution. These results speed up the dynamic response of the HLC lens. The introduction of blend alignment layer decreases the focus and defocus times of the HLC lens by 15% and 34%, respectively. Moreover, the operation voltage of the HLC lens for achieving the shortest focal length is reduced by ∼40%. The decreased switching time is verified by calculating the transient phase conversions of HLC lenses with various viscosities. The calculated results correspond to the experimental results. The blend alignment layer did not degrade the lens and focusing qualities of the HLC lens. Long-term observation revealed that the NP aggregation state remained similar for the LC sample with NPs suspended in the alignment layer. By contrast, NP aggregation spontaneously proceeded and connected networks appeared with time for the LC sample with NPs suspended in LCs. The blend alignment layer can improve the operation voltage and dynamic response of a LC device and prevent device deterioration over time.

Liquid crystalline lipid nanoparticle promotes the photodynamic activity of gallium protoporphyrin against S. aureus biofilms.

Antimicrobial photodynamic therapy (aPDT) has emerged as an innovative strategy to combat antibiotic resistant microbes; yet aPDT efficacies against biofilms are sub-optimal due to inability of photosenstizers to reach microbes embedded in biofilm matrix. To overcome this challenge, liquid crystal lipid nanoparticles (LCNP) were employed in this study as a smart, biocompatible and triggerable delivery system for the new photosensitizer gallium protoporphyrin (GaPP), due to their capabilities in promoting efficient antimicrobial delivery to biofilms. The relationship between GaPP loading of LCNP, reactive oxygen species (ROS) production and the in vitro antibacterial activity against two antibiotic resistant Staphylococcus aureus strains was established. LCNP substantially improved the antibacterial activity of GaPP, completely eradicating S. aureus and MRSA planktonic cultures, using a GaPP concentration of 0.8μM and light dose 1.9J/cm2. At the same concentration and light dose, unformulated GaPP triggered only a 4 log10 and 2 log10 reduction in respective planktonic cultures. Most importantly, the activity of GaPP against biofilms was enhanced by 2-fold compared to unformulated GaPP, reducing the viability of S. aureus and MRSA biofilms by 8 log10 and 5 log10, respectively. The biosafety of photoactivated GaPP-LCNP was evaluated against human fibroblasts, which indicated a high safety profile of the treatment. Therefore, these findings encourage further investigations of GaPP-LCNP as a potential treatment for localized chronic infections.

Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine-Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro.

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine–phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN, P53, and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.

Liquid Crystal Nanoparticle Conjugates for Scavenging Reactive Oxygen Species in Live Cells.

The elevated intracellular production of or extracellular exposure to reactive oxygen species (ROS) causes oxidative stress to cells, resulting in deleterious irreversible biomolecular reactions (e.g., lipid peroxidation) and disease progression. The use of low-molecular weight antioxidants, such as 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), as ROS scavengers fails to achieve the desired efficacy because of their poor or uncontrolled cellular uptake and off-target effects, such as dysfunction of essential redox homeostasis. In this study, we fabricated a liquid crystal nanoparticle (LCNP) conjugate system with the fluorescent dye perylene (PY) loaded in the interior and poly (ethylene glycol) (PEG) decorated on the surface along with multiple molecules of TEMPO (PY-LCNP-PEG/TEMPO). PY-LCNP-PEG/TEMPO exhibit enhanced cellular uptake, and efficient ROS-scavenging activity in live cells. On average, the 120 nm diameter PY-LCNPs were conjugated with >1800 molecules of TEMPO moieties on their surface. PY-LCNP-PEG/TEMPO showed significantly greater reduction in ROS activity and lipid peroxidation compared to free TEMPO when the cells were challenged with ROS generating agents, such as hydrogen peroxide (H2O2). We suggest that this is due to the increased local concentration of TEMPO molecules on the surface of the PY-LCNP-PEG/TEMPO NPs, which efficiently bind to the plasma membrane and enter cells. Overall, these results demonstrate the enhanced capability of TEMPO-conjugated LCNPs to protect live cells from oxidative stress by effectively scavenging ROS and reducing lipid peroxidation.

Thermal and Electro-Optical Properties of Size Dependent Nickel Nanoparticle Doped Blue Phase Liquid Crystals

In present work, effect of nickel nanoparticles size on blue phase stabilization and its electric-optical properties has been demonstrated in In plane switching (IPS) configuration of liquid crystal cells. Variation in phase transitions and their textural behavior after doping of nickel nanoparticles of sizes 20nm and 40nm in pure blue phase liquid crystal was observed under polarizing optical microscope in IPS cells and compared the results with already reported data in indium tin oxide coated glass plate cells. Blue phase range has been widened after doping of both size of nickel nanoparticles and maximum BP range found is 6.5oC and 6.3oC in 20nm and 40nm-BPLC composites respectively in IPS cells. Voltage-transmission data has been taken for pure blue phase liquid crystal and nickel nanoparticles doped blue phase liquid crystal systems at a particular frequency and further various electro-optical parameters have been measured.

Greenly synthesized porous carbon nanoparticle (bio‐waste‐based)‐doped nematic liquid crystal composite with optimized electric and electro‐optical properties for devices

AbstractThe present investigation on the impact of porous carbon nanoparticles (PCNPs) on a room temperature nematic liquid crystalline compound (TP‐188‐01) reports extensive electro‐optical analysis of composite followed by dielectric and luminescence study as well. The pure nematic compound has been doped with 0.1%, 0.25%, and 0.5% of PCNPs (spherical), which have been synthesized by green synthesis technique without use of any activating agents. Low‐frequency dielectric analysis (50 Hz to 1 kHz) has been done to confirm ion generation with increase in PCNS concentration. The dielectric data also indicate preferential orientation of molecules from homogeneous to homeotropic alignment, which can be used in performance optimization of electro‐optical devices. The analysis of dielectric data also illustrates the application of PCNS‐doped systems in circuits operating at high voltages. Diffusion coefficient, mobility, and DC conductivity have been further examined to support the above observations. A significant decrease (of about 47%) in the response time of porous carbon nanoparticle liquid crystal (NP‐LC) composites has also been observed. The photoluminescence spectrum of NP‐LC composites as a function of carbon nanosphere (CNS) concentration has shown Quenching (following the Stern–Volmer quenching mechanism) in the luminescence intensity with increasing CNS concentration. The highly improved response time and quenching in the luminescence intensity further make the PCNS‐doped LC composites as ideal materials to be used in devices, encouraging LC‐aided green nanotechnology.

Thermodynamic and spectroscopic characterization of a weakly polar liquid crystalline compound dispersed with polyvinyl pyrrolidone capped gold nanoparticles

In the present study a deliberate attempt has been made to examine the consequences of dispersion of gold nanoparticles in an azoxybenzene-based nematic liquid crystal, namely 4,4′- di pentyl azoxy benzene. Investigations were made on gold nanoparticles doped nematic liquid crystals analysing differential scanning calorimetry, polarized light microscopy, ultraviolet–visible absorption spectroscopy, photoluminescence and Fourier-transform infrared spectroscopy (FTIR). Gold nanoparticles of different concentrations 0.25, 0.5, and 1.0 wt% were dispersed in pure 4,4′- di pentyl azoxy benzene, and it was observed in the experiment that no significant change occurs in the crystal to nematic phase (Cr-Ne) transition temperature with the increase in gold nanoparticles concentration. However, the nematic to isotropic (Ne-Iso) transition temperature decreases significantly with the increase in gold nanoparticles concentration. This study reports around 76% increase in ultraviolet–visible absorbance and 46% enhancement of photoluminescence intensity with the suitable amount of gold nanoparticles dispersion in 4,4′- di pentyl azoxy benzene. The surface plasmonic resonance (SPR) and re-excitation of 4,4′- di pentyl azoxy benzene molecule due to collision with gold nanoparticles has been accredited to the escalation in photoluminescence intensities.

Liquid Crystal Nanoparticles Enhance Tobramycin Efficacy in a Murine Model of Pseudomonas aeruginosa Biofilm Wound Infection.

Chronic Pseudomonas aeruginosa wound infections are highly prevalent and often untreatable due to biofilm formation, resulting in high antimicrobial tolerance. Standard antibiotic therapy for P. aeruginosa infections involves tobramycin, yet it is highly ineffective as monotherapy as tobramycin cannot penetrate the biofilm to elicit its antimicrobial effect. Lipid liquid crystal nanoparticles (LCNPs) have previously been shown to increase the antimicrobial efficacy and penetration of tobramycin against P. aeruginosa biofilms in vitro and ex vivo. Here, for the first time, we have developed a chronic P. aeruginosa biofilm infection in full-thickness wounds in mice to examine the potential of LCNPs to improve the effect of tobramycin, preclinically. After three doses, administered once a day, tobramycin-LCNPs significantly reduced the P. aeruginosa bacterial load in murine wounds 1000-fold more than unformulated tobramycin, which in turn showed no significant difference to the saline control treatment. Consistent with the improved P. aeruginosa eradication, the tobramycin-LCNPs promoted wound healing. In comparison to previous in vitro and ex vivo data, we show a strong in vitro-in vivo correlation between P. aeruginosa biofilm infection models. The enhanced activity of tobramycin-LCNPs in vivo in the preclinical murine model demonstrates the strong potential of LCNPs as a next-generation formulation approach to improve the efficacy of tobramycin against P. aeruginosa biofilm wound infections.

Liquid crystal nanoparticle platform for increased efficacy of cationic antimicrobials against biofilm infections

Bacterial biofilm infections tolerate high concentrations of antibiotics and are insidiously challenging to treat. Liquid crystal nanoparticles (LCNPs) advance the efficacy of tobramycin in biofilm-related infections by increasing the penetration of antibiotics across the biofilm matrix. Herewith, we develop the LCNPs as a platform technology, demonstrating that the LCNPs can increase the efficacy of two antibiotic classes (i.e. aminoglycosides and colistin) in P. aeruginosa biofilm infections. In C. elegans, the LCNPs potentiated the antimicrobial effect and significantly improved the survival of the nematodes. In mice with a full-thickness excisional wound, LCNPs were non-toxic and did not impair wound repair. Compared to the unformulated antibiotic treatment, tobramycin-LCNPs reduced the chronic bacterial load by 100-fold in the wound. This was also emulated in an ex vivo P. aeruginosa porcine wound infection model. The LCNPs represent a versatile platform technology that improves the efficacy of cationic antibiotics against biofilm infections utilizing multiple administration routes.

Nanoparticle-Induced Property Changes in Nematic Liquid Crystals.

Doping liquid crystals with nanoparticles is a widely accepted method to enhance liquid crystal’s intrinsic properties. In this study, a quick and reliable method to characterise such colloidal suspensions using an optical multi-parameter analyser, a cross-polarised intensity measurement-based device, is presented. Suspensions characterised in this work are either plasmonic (azo-thiol gold AzoGNPs) or ferroelectric Sn2P2S6 (SPS) nanoparticles in nematic liquid crystals. The elastic constants and rotational viscosity showed nonlinear dependence on the concentration of AzoGNPs, initially increasing at lower concentrations and then decreasing at higher concentrations, indicating some degree of particle aggregation. For the SPS suspension, the elastic constant decreased with doping, while the rotational viscosity increased, in agreement with previous findings. Through viscosity measurements, the stability of SPS suspension over ten years is also highlighted.

Characterization of thermal, electro optical and photoluminescent properties of nematic liquid crystal doped with gold nano particles

A complete study based on the thermodynamical, electro-optical photoluminescent concert of gold nano-particle (G-NPs) doped nematic liquid was investigated in the investigate work. The effect of gold nano-particles with concentration dispersion on thermal, electro-optical and dielectric behaviour successfully investigated. The small amount of diffusion of gold nano-particles in EBBA nematic liquid crystal reduced the transition temperature of nematic-isotropic phase. The gold nano-particles as a dopant increases the functional surface area of the material and strong the excitation reflections. Gold nano-particles enhanced the electro-optical and photoluminescence properties at the different biasing.

Effect of size and concentration of magnetic nanoparticles on blue phase stabilization and electro-optical properties in blue phase liquid crystalline nanocomposites

Blue phase liquid crystal material having a wide blue phase range of 7 °C was prepared in a binary mixture of nematic and chiral nematic liquid crystals with optimization of chiral dopant concentration. Magnetic nanoparticles of size 20 nm, 40 nm in varying concentrations (<0.5 wt %) could successfully stabilize the blue phase temperature range. Interestingly, the BP stability increases approximately 7.8 °C with an increase in nanoparticles concentration up to a critical concentration (0.1 wt %) and then gradually decreases at higher concentrations of nickel nanoparticles. A detailed comparative electro-optical study of pure blue phase liquid crystal and size dependent nickel nanoparticles doped blue phase liquid crystals is accomplished. The transmission of light increases up to 42–45% for nickel nanoparticles doped blue phase liquid crystal samples than pure blue phase liquid crystal with negligible residual birefringence. An increase in isotropic temperature was noticed in 40 nm nickel nanoparticles doped sample. Also an improvement in threshold voltage, induced birefringence, contrast ratio and Kerr constant with doping of nickel nanoparticles was observed. The present study is a synergistic correlation of size and concentration of nickel nanoparticles with blue phase liquid crystals and sufficiently productive for developing nanoparticles doped blue phase liquid crystal optical devices in future. • Size and concentration dependent magnetic nanoparticles stabilised blue phase liquid crystals are prepared and studied. • 7.8 °C wide BP range was observed using Ni NPs in BPLCs. • Variation in phase transition temperatures and BP range was noticed with variation in concentration and size of NPs. • An improvement in switching voltage, contrast ratio, birefringence and Kerr constant was observed by stabilization of BPLCs through Ni NPs.

Smectic-A to chiral smectic-C∗ phase transition in the mixture of ferroelectric liquid crystal and ferromagnetic nanoparticles

Experimental results showed the significant impact of ferromagnetic nanoparticles on the smectic-A to chiral smectic-C∗ (SmA-SmC∗) phase transition. This article presents the thermodynamical description in the mixture of ferroelectric liquid crystal and ferromagnetic nanoparticles. The model is based on Flory-Huggins free energy of isotropic mixing and Landau free energy. The impact of ferromagnetic nanoparticles on the spontaneous polarization, tilt angle, transition temperature and dielectric susceptibility near the SmA-SmC∗ phase transition is discussed. Various topologies in the phase diagrams are discussed clearly. Both the qualitative quantitative agreement between experiments and theory are observed.

High dielectric properties, TiO2 nanoparticles doped PDLC devices for lower switching voltage

ABSTRACT Polymer dispersed liquid crystal (PDLC) films were prepared using a nematic liquid crystal, photo-curable polymer and TiO2 nanoparticles by polymerisation-induced phase separation (PIPS) method. Electro-optical properties of doped and undoped samples including transmittance, driving voltage, contrast ratio and response time of the transmittance-voltage were measured, compared and analysed. The morphology of polymer network has been investigated by means of SEM. The phase separation of LC droplets was found to be dependent on the content of prepolymer, LC and nanoparticles used. The high dielectric properties and high refractive index of TiO2 nanoparticles make PDLC have low driving voltage and high contrast. In particular, the nanoparticles concentration can be optimised to obtain promising electronic materials with minimum threshold and high contrast for display applications.

Fréedericksz Transitions in 6CB Based Ferronematics-Effect of Magnetic Nanoparticles Size and Concentration.

In this paper, results acquired from capacitance measurements performed on composites based on nematic liquid crystal 4-cyano-4′-hexylbiphenyl (6CB) and spherical iron oxide nanoparticles of various sizes are presented. Electric and magnetic Fréedericksz transitions, as well as structural transitions in combined electric and magnetic fields, were investigated. The obtained results showed the lowering of the threshold magnetic field with an increase in the volume concentration of nanoparticles. Estimations based on results obtained from measurements suggest soft anchoring between liquid crystal director and nanoparticles magnetization vector.

Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis-Related Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa biofilms cause persistent and chronic infections, most known clinically in cystic fibrosis (CF). Tobramycin (TOB) is a standard anti-pseudomonal antibiotic; however, in biofilm infections, its efficacy severely decreases due to limited permeability across the biofilm matrix. Herewith, a biomimetic, nanostructured, lipid liquid crystal nanoparticle-(LCNP)-formulation is discovered to significantly enhance the efficacy of TOB and eradicate P. aeruginosa biofilm infections. Using an advanced, biologically-relevant co-culture model of human CF bronchial epithelial cells infected with P. aeruginosa biofilms at an air-liquid interface, nebulized TOB-LCNPs completely eradicated 1× 109 CFU mL-1 of P. aeruginosa after two doses, a 100-fold improvement over the unformulated antibiotic. The enhanced activity of TOB is not observed with a liposomal formulation of TOB or with ciprofloxacin, an antibiotic that readily penetrates biofilms. It is demonstrated that the unique nanostructure of the LCNPs drives the enhanced penetration of TOB across the biofilm barrier, but not through the healthy lung epithelium barrier, significantly increasing the available antibiotic concentration at the site of infection. The LCNPs are an innovative strategy to improve the performance of TOB as a directed pulmonary therapy, enabling the administration of lower doses, reducing the toxicity, and amplifying the anti-biofilm activity of the anti-pseudomonal antibiotic.

Protective Liquid Crystal Nanoparticles for Targeted Delivery of PslG: A Biofilm Dispersing Enzyme.

The glycoside hydrolase, PslG, attacks and degrades the dominant Psl polysaccharide in the exopolymeric substance (EPS) matrix of Pseudomonas aeruginosa biofilms and is a promising therapy to potentiate the effect of antibiotics. However, the need for coadministration with an antibiotic and the potential susceptibility of PslG to proteolysis highlights the need for an effective delivery system. Here, we compared liposomes versus lipid liquid crystal nanoparticles (LCNPs) loaded with PslG and tobramycin as potential formulation approaches to (1) protect PslG from proteolysis, (2) trigger the enzyme's release in the presence of bacteria, and (3) improve the total antimicrobial effect in vitro and in vivo in a Caenorhabditis elegans infection model. LCNPs were an effective formulation strategy for PslG and tobramycin that better protected the enzyme against proteolysis, triggered and sustained the release of PslG, improved the antimicrobial effect by 10-100-fold, and increased the survival of C. elegans infected with P. aeruginosa. Digestible LCNPs had the advantage of triggering the enzyme's release in the presence of bacteria. However, compared to nondigestible LCNPs, negligible differences arose between the LCNPs' ability to protect PslG from proteolysis and potentiate the antimicrobial activity in combination with tobramycin. In C. elegans, the improved antimicrobial efficacy was comparable to tobramycin-LCNPs, although the PslG + tobramycin-LCNPs achieved a greater than 10-fold reduction in bacteria compared to the unformulated combination. Herewith, LCNPs are showcased as a promising protective delivery system for novel biofilm dispersing enzymes combined with antibiotics, enabling infection-directed therapy and improved performance.

Broadband reflection in polymer-stabilized cholesteric liquid crystal film with zinc oxide nanoparticles film thermal diffusion method

ABSTRACT Broadband reflective films were prepared by thermal diffusion of zinc oxide nanoparticles (ZnO NPs) in chiral nematic liquid crystals (N*-LCs). Ultraviolet (UV) light was irradiated in the direction of the thickness of the liquid crystal film to form the intensity gradient of UV light, to induce the gradient distribution of the pitch. The effects of the content of ZnO NPs, the UV light intensity, the UV irradiation time, the monomer concentration, and the diffusion temperature on the reflective bandwidth of the sample were studied. The results show that the appropriate content of ZnO NPs and the effective UV radiation intensity is beneficial to the broadband reflection of the sample. To elucidate the mechanism of photoinduced pitch gradients, the fracture surface of the sample film was observed by scanning electron microscopy (SEM), and the influence of experimental conditions on the broadband reflection performance of N*-LCs films was analysed theoretically.

Reprogramming Cancer Stem-like Cells with Nanoforskolin Enhances the Efficacy of Paclitaxel in Targeting Breast Cancer.

Cancer stem-like cells (CSCs) have emerged as an important target for breast cancer therapy owing to their self-renewability, proliferation, and elevated chemoresistance properties. Here, we present a strategy of eliminating CSCs by differentiation therapy where "forced differentiation" reprograms CSCs so that they lose their intrinsic properties and become susceptible for conventional chemotherapeutic drugs. In this study, we report that a conventional chemotherapeutic paclitaxel enhances the stemness of CSCs, while a phytochemical forskolin being essentially nontoxic to CSCs possesses the intrinsic ability to reprogram them. To achieve simultaneous targeting of CSCs and bulk tumor cells, we used a co-delivery system where liquid crystal nanoparticles (LCN) were co-encapsulated with both paclitaxel and forskolin. LCN showed higher uptake, retention, and penetration potential in CSCs overcoming their high drug efflux property. Moreover, LCN improved the pharmacokinetic parameters of forskolin, which otherwise had very low retention and bioavailability. Forskolin-loaded LCN forced CSCs to exit from their mesenchymal state, which reduced their stemness and chemosensitized them while inhibiting E-cadherin-mediated survival and tumor-initiating potential as well as reversing paclitaxel-induced stemness. We further showed that upon administration of paclitaxel and forskolin co-loaded LCN to an orthotropic xenograft mouse model, the nanomedicine showed enhanced passive tumor targeting capability with very potent antitumor activity that eradicated small solid tumor in a single dose and showed no sign of tumor relapse or systemic toxicity over a long period. Overall, these findings give a proof of concept that co-delivery of forskolin and paclitaxel in a single nanoformulation can achieve overall tumor targeting where forskolin can efficiently reprogram/differentiate CSCs and paclitaxel can induce cytotoxicity in both differentiated CSCs and bulk tumor cells simultaneously. Hence, this study can provide a nanoformulation that can offer an efficient strategy for cancer therapy.