Nanoencapsulation Of Drugs Research Articles

Fabrication of ibuprofen/naringenin-coloaded into zein/sodium caseinate nanoparticles: evaluation of antiproliferative activity and apoptosis induction in liver cancer cells

Nowadays, liver cancer is one of the most disturbing types of cancer that can affect either sex. Nanoparticles (NPs) of zein/sodium caseinate incorporating ibuprofen (IBU) and naringenin (NAR) have improved bioavailability and a high encapsulation efficiency (EE%). These nanoparticles are uniformly spherical. In vitro, cytotoxicity analysis on HepG2 cell lines, which are used to study human liver cancer, shows that encapsulated drugs (86.49% ± 1.90, and 78.52% ± 1.98 for NAR and IBU, respectively) have significantly lower IC50 values than individual drugs or their combined free form. In addition, the combination indices of 0.623 and 0.155 for IBU and NAR, respectively, show that the two have joint beneficial effects. The scratch wound healing assay results also show that the free drugs and the engineered NPs have a more significant anti-migratory effect than the untreated cells. The designed nanoparticles also reduce angiogenesis and proliferation while inducing apoptosis, according to in vitro results. In conclusion, a new approach to treating liver cancer may lie in the nanoencapsulation of numerous drugs within nanoparticles.

Biologically based strategies for overcoming in vivo barriers with functional nano-delivery systems.

Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non-sized or nano-encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio-based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off-target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm.

A new rapid-release SMA-activated micropump with incorporated microneedle arrays and polymeric nanoparticles for optimized transdermal drug delivery

Recent research in Transdermal drug delivery (TDD) systems has predominantly focused on microneedles (MNs) and nanoencapsulated drugs, which offer painless, gradual drug release but may not cater to quick-release drug demands. This study introduces an innovative approach to expedite the TDD process by merging a new rapid-release micropump, MNs, and nanoencapsulation into a modular framework. The fabrication and evaluation of a 3D printed shape memory alloy (SMA)-activated micropump combined with ibuprofen-loaded polymeric nanoparticles delivered via integrated MNs is thereby discussed. The system utilizes an SMA spring wire to actuate a loaded spring which drives an elastic membrane into a chamber integrated with an array of stereolithography (SLA) 3D printed MNs, facilitating painless injection into the dermis layer of the skin. The MNs array is optimized with finite element analysis (FEA) to minimize discomfort from the needles while maximizing the drug load into the skin. The system’s performance is characterized through high-speed camera imaging, and an average membrane speed of 0.28 m/s is developed. The system’s effectiveness is finally evaluated via a short time frame (5 minutes) ex vivo skin deposition experiment using Franz diffusion cells and rat skin, revealing almost twice the ibuprofen deposition in skin layers with polymeric nanoparticles compared to an untreated solution. The rapid response and demonstrated efficacy of this concept aims to provide a framework for potentially extending this application for transdermal insulin injection.

Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer

Nowadays, breast cancer is considered one of the most upsetting malignancies among females. Encapsulation of celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles (NPs) produce homogenous and spherical nanoparticles with good encapsulation efficiencies (EE %) and bioavailability. In vitro cytotoxicity study conducted on human breast cancer MDA-MB-231 cell lines revealed that there was a significant decline in the IC50 for encapsulated drugs when compared to each drug alone or their free combination. In addition, results demonstrated that there is a synergism between CXB and PDG as their combination indices were 0.62251 and 0.15493, respectively. Moreover, results of scratch wound healing assay revealed enhanced antimigratory effect of free drugs and fabricated NPs in comparison to untreated cells. Furthermore, In vitro results manifested that formulated nanoparticles exhibited induction of apoptosis associated with reduced angiogenesis, proliferation, and inflammation. In conclusion, nanoencapsulation of multiple drugs into nanoparticles might be a promising approach to develop new therapies for the managing of triple negative breast cancer.

Alginate/chitosan/diallyl disulfide nanoparticles: Synthesis, characterization and their anti-inflammatory efficacy on TPA-induced acute mouse ear inflammation

Diallyl disulfide (DADS) is a garlic (Allium sativum) derived potent anti-inflammatory compound. Due to poor bioavailability, its biological application has limitations. Nanoencapsulation of therapeutic drugs is a promising approach to increase their bioavailability, specificity, and efficacy. In our approach, DADS was coated with the natural polymers alginate and chitosan into a polyelectrolytic nano-formulation. Characterization of the nanoparticles showed monodispersed nanosized particles and a release study at pH 5.5 revealed sustained release of the drug. To investigate the anti-inflammatory efficacy of the DADS nanoparticle (DADS-NP), a comparative study with the free drug was conducted on a mouse model of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ear edema. The results indicated that DADS-NP significantly alleviated TPA-induced ear edema more effectively than the free drug of the same concentration. Further, mechanistic studies indicated that DADS-NP more efficiently downregulated the phosphorylation of p38 mitogen activated protein kinase which subsequently restricted the activation and nuclear translocation of downstream transcription factor nuclear factor- кB (NF-кB). This downregulated the expression of pro-inflammatory proteins cyclooxygenase-2 (COX-2) and inducible-nitric oxide synthase (i-NOS) thus mitigating ear edema. Cellular internalization of the DADS-NP was observed. Collectively, our studies indicate enhanced anti-inflammatory efficiency of DADS-NP when compared to free DADS suggesting enhanced stability and bioavailability.

Gastrointestinal Microenvironment Responsive Nanoencapsulation of Probiotics and Drugs for Synergistic Therapy of Intestinal Diseases.

The gut microbiota are prominent in preserving intestinal environmental homeostasis and managing human health, and their dysbiosis has been directly related to many kinds of intestinal diseases. Probiotics-based therapy appears as a promising approach for the treatment of gut microbiota dysbiosis, while it always suffers from limited bioavailability and therapeutic effect after oral administration. Herein, we presented a facile and safe strategy to treat colitis by nanoencapsulation of probiotics and an anti-inflammatory agent, 5-aminosalicylic acid (5-ASA), within the gastrointestinal microenvironment responsive alginate polysaccharide. Because of acid resistance, the alginate-based coating protected probiotics from the harsh gastric condition. The coating could be disintegrated to release probiotics and 5-ASA upon arriving in the intestinal tract, where the pH is normally higher than 5. In the dextran sulfate sodium-induced colitis mouse model, probiotics recovered their bioactivities and acted together with anti-inflammatory 5-ASA to alleviate colitis by upregulating microbiota richness and diversity, reducing expression of proinflammatory cytokines, and restoring intestinal barriers. This work demonstrated the synergistic therapy of intestinal diseases based on alginate-encapsulated probiotics and a clinical drug, which provided an extensive method to improve the therapeutic effect of oral microecologics.

Potentiation of Folate-Functionalized PLGA-PEG nanoparticles loaded with metformin for the treatment of breast Cancer: possible clinical application.

Folate receptor expression increase up to 30% in breast cancer cells and could be used as a possible ligand to couple to folate-functionalized nanoparticles. Metformin (Met) is an anti-hyperglycemic agent whose anti-cancer properties have been formerly reported. Consequently, in the current study, we aimed to synthesize and characterize folate-functionalized PLGA-PEG NPs loaded with Met and evaluate the anti-cancer effect against the MDA-MB-231 human breast cancer cell line. FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes. MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs. Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.

Preparation, characterization, and in-vitro cytotoxicity of nanoliposomes loaded with anti-tubercular drugs and TGF-β1 siRNA for improving spinal tuberculosis therapy

BackgroundTuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Overexpression of transforming growth factor (TGF)-β1 has a primary immunomodulatory function in human tuberculosis. This work aimed to develop nanoliposomes to facilitate the delivery of anti-tubercular products to THP-1-derived human macrophages as Mycobacterium host cells and to evaluate drug efficiencies as well as the effects of a TGF-β1-specific short interfering RNA (siRNA) delivery system employing nanoliposomes.MethodsIn the current study, siTGF-β1 nanoliposomes loaded with the anti-TB drugs HRZ (isoniazid, rifampicin, and pyrazinamide) were prepared and characterized in vitro, determining the size, zeta potential, morphology, drug encapsulation efficiency (EE), cytotoxicity, and gene silencing efficiency of TGF-β1 siRNA.ResultsHRZ/siTGF-β1 nanoliposomes appeared as smooth spheres showing the size and positive zeta potential of 168.135 ± 0.5444 nm and + 4.03 ± 1.32 mV, respectively. Drug EEs were 90%, 88%, and 37% for INH, RIF, and PZA, respectively. Meanwhile, the nanoliposomes were weakly cytotoxic towards human macrophages as assessed by the MTT assay. Nanoliposomal siTGF-β1 could significantly downregulate TGF-β1 in THP-1-derived human macrophages in vitro.ConclusionThese findings suggested that HRZ-loaded nanoliposomes with siTGF-β1 have the potential for improving spinal tuberculosis chemotherapy via nano-encapsulation of anti-TB drugs.

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs.

The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics. All isolates showed resistance to one or more antibiotics and S. enterica ser. Typhimurium isolate had the highest resistance to the panel of antibiotics tested. Major resistance mechanisms identified were efflux pump and beta-lactamase enzyme activities. Staphylococcus isolates showed complete hemolysis and strong biofilm formation, while Salmonella isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of S. aureus M12 and S. enterica ser. Typhimurium bacteria were subsequently tested against combinations of antibiotics and potentiating adjuvants for improved antibacterial efficacy using a checkerboard assay, and their fractional inhibitory concentration index (FICI) was calculated. A combination of chitosan and silica nanoparticles containing tetracycline (TET) and efflux pump inhibitor chlorpromazine (CPZ), respectively, was characterized for physicochemical properties and effectiveness against MDR Salmonella enterica ser. Typhimurium isolate. This combination of nano-encapsulated drugs improved the antibacterial efficacy by inhibiting AMR mechanisms (efflux activity, beta-lactamase enzyme activity, and hydrogen sulfide (H2S) production) and reducing intracellular pathogen load by 83.02 ± 14.35%. In conclusion, this study sheds light on the promising applicability of nanoparticle-enabled combination therapy to combat multidrug-resistant pathogens encountered in animal agriculture.

Acute Myeloid Leukemia Mutations and Future Mechanistic Target to Overcome Resistance.

Cytogenetics and mutation identification in acute myeloid leukemia have allowed for more targeted therapy. Many therapies have been approved by the FDA in the last 3 years including gilteritinib and azacitidine but the overall survival has remained stagnant at 25%. The inability to achieve complete remission was related to the residual leukemic stem cells (LSCs). Thus, the relationship between bone marrow niche and LSCs must be further explored to prevent treatment relapse/resistance. The development of immunotherapy and nanotechnology may play a role in future therapy to achieve the complete remission. Nano-encapsulation of drugs can improve drugs' bioavailability, help drugs evade resistance, and provide combination therapy directly to the cancer cells. Studies indicate targeting surface antigens such as CLL1 and CD123 using chimeric antibody receptor T cells can improve survival outcomes. Finally, new discoveries indicate that inhibiting integrin αvβ3 and acid ceramidase may prove to be efficacious.

An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation.

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.

The potential role of nanomedicine on COVID-19 therapeutics.

The potential role of nanomedicine on COVID-19 therapeutics.

Promising Role of Nano-Encapsulated Drugs for Spinal Cord Injury.

Nanomaterials have been utilized for the drug delivery in the central nervous system (CNS), and many research investigators are currently focussing on this specified area. There has been a lot of advancement in the nanoparticle-mediated drug delivery to the brain. Neuronal injuries including spinal cord injury (SCI) and their targeted therapies are still in its infancy on this planet. SCI has been known to cause axonal damage followed by the loss of communication between CNS and other non-neuronal systems. SCI has been critically associated with prolonged inflammation, sensory dysfunction, and motor impairment in SCI patients. There has been a critical crosstalk in SCI and blood brain barriers (BBBs) for drug absorption and distribution in patients. There is a paucity of possible therapies for proper intervention of SCI due to selective permeability of the drugs across BBB. Nanomaterials are contemplated in the drug delivery system for SCI. In addition, self-assembled nanomicelles, lipid nanoparticles, and other co-polymers have now been explored for neuronal injuries. This review focuses on the promising approach and/or role of nanodrug delivery to target SCI in both in vitro and in vivo models.

Spray-Dried, Nanoencapsulated, Multi-Drug Anti-Tuberculosis Therapy Aimed at Once Weekly Administration for the Duration of Treatment.

Aiming to improve the treatment outcomes of current daily tuberculosis (TB) chemotherapy over several months, we investigated whether nanoencapsulation of existing drugs would allow decreasing the treatment frequency to weekly, thereby ultimately improving patient compliance. Nanoencapsulation of three first-line anti-TB drugs was achieved by a unique, scalable spray-drying technology forming free-flowing powders in the nanometer range with encapsulation efficiencies of 82, 75, and 62% respectively for rifampicin, pyrazinamide, and isoniazid. In a pre-clinical study on TB infected mice, we demonstrate that the encapsulated drugs, administered once weekly for nine weeks, showed comparable efficacy to daily treatment with free drugs over the same experimental period. Both treatment approaches had equivalent outcomes for resolution of inflammation associated with the infection of lungs and spleens. These results demonstrate how scalable technology could be used to manufacture nanoencapsulated drugs. The formulations may be used to reduce the oral dose frequency from daily to once weekly in order to treat uncomplicated TB.

Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia.

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML.

Enhanced anticancer potency by combination chemotherapy of HT-29 cells with biodegradable, pH-sensitive nanoparticles for co-delivery of hydroxytyrosol and doxorubicin

A potential approach for clinical colon cancer therapy is combination chemotherapy. In this study, a biodegradable and pH-responsive nano-carrier was designed for co-delivery of Doxorubicin hydrochloride (DOX) and Hydroxytyrosol (HT) in HT-29 colon cancer cells. For this purpose, Poly (lactide-co-glycolic acid-co-acrylic acid) (PLGA-co-PAA) was synthesized by radical AA telomerization in the presence of mercaptoethanol (ME), followed by the ring-opening polymerization (ROP) of lactide and glycolide in the presence of PAA-OH as a chain transfer agent. Nanoparticles with homogeneous spherical morphology and an average diameter of around 18 nm were obtained; cellular uptake of DOX@HT-loaded nanoparticles was more than 94%. Cell cycle analysis and DAPI staining results revealed a high amount of apoptosis on HT-29 cancer cells treated with the dual drug-loaded nanoparticles in comparison to free drugs and single drug-loaded nano-formulations. RT-PCR analysis indicated that the expression levels of hTERT, CREB1 and CREB2 genes were significantly down-regulated in the presence of nano-encapsulated drugs versus free drugs in the HT-29 cell line. Moreover, results revealed that DOX@HT NPs inhibited gene expression more efficiently than single forms. All these results confirmed that these pH-responsive biodegradable nanoparticles are suitable for combination chemotherapy and further in vivo studies in future.

Modified montmorillonite nanolayers for nano-encapsulation of biomolecules

Vitamin B6 was nano-encapsulated in between modified montmorillonite nanolayers. Results indicated that electrostatic interaction forces dominate the adsorption onto different sites of the nanolayers. The successful nano-encapsulation was achieved when the interlayers spaces of the nanolayer were saturated with cations of Na+ or Ca2+ resulted in adsorption of vitamin B6 in between nanosheets. At these conditions, controlled pH-responsive desorption properties were detected and vitamin B6 was released mostly from the interlayer spaces. The presented modified montmorillonite could be used for nanoencapsulation of drugs and biomolecules with high protection of carrying materials during storage and even through the digestion process.

Drug-Loaded Biocompatible Nanocarriers Embedded in Poloxamer 407 Hydrogels as Therapeutic Formulations.

Hydrogels are three-dimensional networks of hydrophilic polymers able to absorb and retain a considerable amount of water or biological fluid while maintaining their structure. Among these, thermo-sensitive hydrogels, characterized by a temperature-dependent sol–gel transition, have been massively used as drug delivery systems for the controlled release of various bioactives. Poloxamer 407 (P407) is an ABA-type triblock copolymer with a center block of hydrophobic polypropylene oxide (PPO) between two hydrophilic polyethyleneoxide (PEO) lateral chains. Due to its unique thermo-reversible gelation properties, P407 has been widely investigated as a temperature-responsive material. The gelation phenomenon of P407 aqueous solutions is reversible and characterized by a sol–gel transition temperature. The nanoencapsulation of drugs within biocompatible delivery systems dispersed in P407 hydrogels is a strategy used to increase the local residence time of various bioactives at the injection site. In this mini-review, the state of the art of the most important mixed systems made up of colloidal carriers localized within a P407 hydrogel will be provided in order to illustrate the possibility of obtaining a controlled release of the entrapped drugs and an increase in their therapeutic efficacy as a function of the biomaterial used.

Nanoencapsulation of Novel Inhibitors of PNKP for Selective Sensitization to Ionizing Radiation and Irinotecan and Induction of Synthetic Lethality

There is increasing interest in developing and applying DNA repair inhibitors in cancer treatment to augment the efficacy of radiation and conventional genotoxic chemotherapy. However, targeting the inhibitor is required to avoid reducing the repair capacity of normal tissue. The aim of this study was to develop nanodelivery systems for the encapsulation of novel imidopiperidine-based inhibitors of the DNA 3'-phosphatase activity of polynucleotide kinase/phosphatase (PNKP), a DNA repair enzyme that plays a critical role in rejoining DNA single- and double-strand breaks. For this purpose, newly identified hit compounds with potent PNKP inhibitory activity, imidopiperidines A12B4C50 and A83B4C63 were encapsulated in polymeric micelles of different poly(ethylene oxide)- b-poly(ε-caprolactone) (PEO- b-PCL)-based structures. Our results showed efficient loading of A12B4C50 and A83B4C63 in PEO- b-PCLs with pendent carboxyl and benzyl carboxylate groups, respectively, and relatively slow release over 24 h. Both free and encapsulated inhibitors were able to sensitize HCT116 cells to radiation and the topoisomerase I poison, irinotecan. In addition, the encapsulated inhibitors were capable of inducing synthetic lethalilty in phosphatase and tensin homologue (PTEN)-deficient cells. We also established the validity of the peptide GE11 as a suitable ligand for active targeted delivery of nanoencapsulated drugs to colorectal cancer cells overexpressing epidermal growth factor receptor (EGFR). Our results show the potential of nanoencapsulated inhibitors of PNKP as either mono or combined therapeutic agents for colorectal cancer.

Co-Delivery of Curcumin and Chrysin by Polymeric Nanoparticles Inhibit Synergistically Growth and hTERT Gene Expression in Human Colorectal Cancer Cells

ABSTRACTNanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in colorectal cancer therapy. Here, two well-known herbal substances, Curcumin (Cur) and Chrysin (Chr), were co-encapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against Caco-2 cancer cells.Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nano-encapsulated drugs on expression level of hTERT in Caco-2 cells.The results showed that free drugs and nano-formulations exhibited a dose-dependent cytotoxicity against Caco-2 cells and especially, Cur–Chr–PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (P < 0.05). Real-time PCR results revealed that Cur, Chr, and combination of Cur–Chr in free and encapsulated forms inhibited hTERT gene expression. Also, it was found that Cur–Chr–PLGA/PEG NPs than free combination forms could further decline hTERT expression in all concentration (P < 0.05).In summary, our study represents the first report of nano-combinational application of the natural herbal substances with a one-step fabricated codelivery system for effective colorectal cancer combinational chemotherapy.