Nanoscale Drug Delivery Systems Research Articles

Comprehensive theoretical prediction of the dynamics and stability properties of Tegafur pharmaceutical agent on the Graphene based nanostructures in aqueous environment

In this study, the molecular dynamics (MD) simulations are applied to elucidate the mechanisms governing the dynamics and binding strength of Tegafur (TG) anticancer drug interacting with two-dimensional carbon-based nanomaterials including hydroxyl (G-OH) and carbonyl (G-CO) functionalized Graphene nanosheets as well as Graphene oxide (GO). It is found that Tegafur drug exhibits the strongest affinity for the adsorption on Graphene oxide in terms of van der walls (vdW) amount energy. Furthermore, the total number of hydrogen bonding (HB) for the interaction of TG drug with GO is more than those with G-OH and G-CO models which be associated with maximum number of contacts between Tegafur molecules and Graphene oxide and higher stability. Based on these results, selection of Graphene oxide nanosheet as the suitable nano-carrier plays an important role in the greater effectiveness of TG drug with further experimental and theoretical investigations of nanoscale drug delivery systems.

The potential role of nanomedicine in lung diseases

Nanomedicine is a rapidly emerging interdisciplinary field in which medicine is coupled with nanotechnology tools and techniques for advanced therapy with the aid of molecular knowledge. Nanoscale drug delivery systems provide a platform to improve the pharmacokinetics and increase the bio-distribution of therapeutic agents to target organs, thereby resulting in improved efficacy while limiting drug toxicity. These systems have revolutionized drug delivery approaches and are exploited for therapeutic purposes to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. Several promising molecular targets that have been identified as potential therapies for acute and chronic respiratory conditions have been limited because of difficulty with delivery systems. In particular, delivery of peptides, proteins, miRNAs to the lung is an ongoing challenge. Hence, it is an attractive strategy to test potential targets by employing a nanotechnology approach. Nanobiotechnology and nanoscience can provide innovative techniques to deliver drugs targeted to the site of inflamed organs. Here we review some of the nanomedicine approaches that have been proposed and studied over the last decade to facilitate the delivery of therapeutic agents specifically for acute and chronic lung diseases. Development of nano-sized carriers including nanoparticles, or liposomes holds great potential for diagnosis and advanced delivery systems for immunomodulation in respiratory diseases; however translational studies are urgently needed to validate the use of nanotechnology for clinical applications.

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops

As the world population grows, there is a need for efficient agricultural technologies to provide global food requirements and reduce environmental toll. In medicine, nanoscale drug delivery systems grant improved therapeutic precision by overcoming biological barriers and enhancing drug targeting to diseased tissues. Here, we loaded nanoscale drug-delivery systems with agricultural nutrients, and applied them to the leaves of tomato plants. We show that the nanoparticles – liposomes composed of plant-derived lipids, penetrate the leaf and translocate in a bidirectional manner, distributing to other leaves and to the roots. The liposomes were then internalized by the plant cells, where they released their active ingredient. Up to 33% of the applied nanoparticles penetrated the leaf, compared to less than one percent of free-molecules applied in a similar manner. In our study, tomato plants treated with liposomes loaded with Fe and Mg overcame acute nutrient deficiency which was not treatable using ordinary agricultural nutrients. Furthermore, to address regulatory concerns regarding airborne nanoparticles, we rationally designed liposomes that were stable only over short spraying distances (less than 2 meters), while the liposomes disintegrated into safe molecular building blocks (phospholipids) over longer airborne distances. These findings support expanding the implementation of nanotechnology for delivering micronutrients to agricultural crops for increasing yield.

Acid-degradable lactobionic acid-modified soy protein nanogels crosslinked by ortho ester linkage for efficient antitumor in vivo

It remains a crucial challenge to achieve efficient cellular uptake and intracellular drug release in tumor cells for the nanoscale drug delivery systems. Herein, acid-degradable nanogels were prepared by cross-linking methacrylated soy protein with an acid-labile ortho ester cross-linker (NG1), and then modified with lactobionic acid (LA) to give tumor-targeted nanogels (NG2). Both NG1 and NG2 displayed excellent stability in neutral environment, while showed pH-triggered degradation behaviors under mildly acidic conditions resulting from the breakage of ortho ester bonds. Doxorubicin (DOX) was successfully loaded into nanogels, which exhibited an accelerated release at low pH. In vitro cell studies demonstrated that LA-modified nanogels could effectively improve cellular internalization, show higher cytotoxicity and apoptosis toward asialoglycoprotein receptor (ASGPR) over-expressed HepG2 cells. In vivo antitumor experimentproved that LA modification could significantly enhance the tumor-targeting ability of nanogels and increase DOX concentration in tumor site, leading to better therapeutic efficacy. Histological analysis further demonstrated that soy protein-based nanogels did not cause any damage to normal organs. Overall, these pH-sensitive and tumor-targeting soy protein-based nanogels can be potential drug carriers for efficient tumor treatment.

Status and future directions in the management of pancreatic cancer: potential impact of nanotechnology.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity. In addition, PDAC tumor tissue is dense and highly resistant to many traditional chemotherapeutic applications, making the disease difficult to treat and impeding options for palliative care. New developments in nanotechnology may offer innovative options for targeted PDAC therapeutic drug delivery. Nanotechnology can be implemented using multimodality methods that offer increased opportunities for earlier diagnosis, precision enhanced imaging, targeted long-term tumor surveillance, and controlled drug delivery, as well as improved palliative care and patient comfort. Nanoscale delivery methods have demonstrated the capacity to infiltrate the dense, fibrous tumor tissue associated with PDAC, increasing delivery and effectiveness of chemotherapeutic agents and reducing toxicity through the loading of multiple drug therapies on a single nano delivery vehicle. This review presents an overview of nanoscale drug delivery systems and multimodality carriers at the forefront of new PDAC treatments.

Gold nanoparticles tethered cinnamic acid: preparation, characterization, and cytotoxic effects on MCF-7 breast cancer cell lines

The main objective of the study is to tether citrate-stabilized gold nanoparticles (CS©GNPs) with cinnamic acid (CA) and evaluating them against MCF-7 breast cancer cells. To achieve CA~CS©GNPs, CS©GNPs prepared were blended with CA under controlled experimental conditions followed by high-throughput characterization. The result from the study demonstrates that positively charged hydrogen moiety present in O–H group of CA provides an opportunity for binding of CS©GNPs via hydrogen bonding evidenced by color change (ruby to light purple) and spectroscopic analysis (UV–visible and FT-IR spectroscopy). The size and shape of CA~CS©GNPs were not the same as CS©GNPs substantiated by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. At the end, cytotoxic and morphological assessment against MCF-7 breast cancer cells shows effective suppression of tumor cells and thereby promoting them as promising nanoscale drug delivery system in near future.

Development of Targeted Nanoscale Drug Delivery System for Osteoarthritic Cartilage Tissue.

Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxy-poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C═C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis.

Polysaccharide Functionalized Single Walled Carbon Nanotubes as Nanocarriers for Delivery of Curcumin in Lung Cancer Cells.

Nanoscale drug delivery systems have emerged as promising alternatives to overcome the problems associated with by conventional chemotherapy for cancer treatment such as poor drug stability and bio-distribution. Herein, we report a single walled carbon nanotubes (SWCNTs) based drug delivery system functionalized with polysaccharides such as alginate (ALG) and chitosan (CHI), which can be loaded with an anticancer drug curcumin (CUR). Modification of SWCNTs renders high drug loading efficiency and sustained drug release, imperative for drug activity. These were characterized through various tools viz, microscopic (transmission electron microscopy, scanning electron microscopy and atomic force microscopy) and zeta potential analysis. Incorporation of CUR inside the modified SWCNTs was studied through Fourier transform infrared spectroscopy, fluorescence and UV-visible spectroscopy. In vitro release studies were conducted to gain an insight into the pH-dependent release behavior of the entrapped CUR from modified SWCNTs. The anti-cancer potential was further demonstrated using human lung adenocarcinoma (A549) cells as a model system. Various cell culture based assays were performed to study the ability of released CUR from modified SWCNTs for inhibiting the cancer cell proliferation by inducing apoptosis.

Copolymeric Micelles Loading Curcumin: Preparation, Characterization and In Vitro Evaluation.

Curcumin (Cur) has potent antitumor activity; however, its clinical use is limited due to its hydrophobicity and instability at physiological pH. In this work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur-loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having excellent water-solubility and good stability at pH 7.4. The freeze-drying powders of the Cur-loaded micelles were easily rehydrated. It was found that Cur was slowly released from the micelles with a cumulative drug release percentage of 78.11% within 14 days and there was no obvious drug burst release. MTT tests showed that, the IC50 values of the Cur-loaded micelles were lower than those of free Cur against cancer cells (MDA-MB-231 cells and 4T1 cells). No matter for cancer cells (MDA-MB-231 cells and 4T1 cells) or healthy cells (L929 cells), cell viabilities were all >90% after incubating with the blank MPEG2K-P(CL-co-LLA) micelles, even at very high micelle concentration (up to 1000 μg/mL), indicating the blank micelles were of no or extremely low cytotoxicity per se. The Cur-loaded micelles were taken up mainly via endocytosis route and the cellular uptake on 4T1 cells increased with incubation time. They could induce more cell apoptosis compared to free Cur. These results suggested that curcumin-loaded MPEG2K-P(CL-co-LLA) micelles may be a potential nanoscale drug delivery system for cancer therapy.

Shape of Nanoparticles as a Design Parameter to Improve Docetaxel Antitumor Efficacy.

It was reported that the shape of nanocarriers played an important role in achieving a better therapeutic effect. To optimize the morphology and enhance the antitumor efficacy, in this study based on the amphiphilic PAMAM- b-OEG codendrimer (POD), docetaxel-loaded spherical and flake-like nanoparticles (DTX nanospheres and nanosheets) were prepared via an antisolvent precipitation method with similar particle size, surface charge, stability, and release profiles. The feed weight ratio of DTX/POD and the branched structure of OEG dendron were suggested to influence the shapes of the self-assembled nanostructures. As expected, DTX nanospheres and nanosheets exhibited strong shape-dependent cellular internalization efficiency and antitumor activity. The clathrin-mediated endocytosis and macropincytosis-dependent endocytosis were proven to be the main uptake mechanism for DTX nanospheres, while it was clathrin-mediated endocytosis for DTX nanosheets. More importantly, DTX nanosheets presented obviously superior antitumor efficacy over nanospheres, the tumor inhibition rate was increased 2-fold in vitro and 1.3-fold in vivo. An approximately 2-fold increase in pharmacokinetic parameter (AUC, MRT, and T1/2) and tumor accumulation were observed in the DTX nanosheets group. These results suggested that the particle shape played a key role in influencing cellular uptake behavior, pharmacokinetics, biodistribution, and antitumor activity; the shape of drug-loaded nanoparticles should be considered in the design of a new generation of nanoscale drug delivery systems for better therapeutic efficacy of anticancer drug.

Therapeutic applications of betulinic acid nanoformulations.

Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad-spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half-life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half-life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems-including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes-have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.

Co-delivery of dihydroartemisinin and docetaxel in pH-sensitive nanoparticles for treating metastatic breast cancer via the NF-κB/MMP-2 signal pathway.

Metastasis is a major barrier in cancer chemotherapy. Prolonged circulation and rapid, specific intracellular drug release are two main goals in the development of nanoscale drug delivery systems to treat metastatic breast cancer. In this study, we investigated the anti-metastasis effect of docetaxel (DTX) in combination with dihydroartemisinin (DHA) in metastatic breast cancer 4T1 cells. We synthesized a pH-sensitive material 4-arm-PEG-DTX with a hydrazone bond and used it to construct nanoparticles that co-deliver DTX and DHA (D/D NPs). The D/D NPs had a mean size of 142.5 nm and approximately neutral zeta potential. The pH-sensitive nanoparticles allowed acid-triggered drug release at the tumor site, showing excellent cytotoxicity (IC50 = 7.0 μg mL−1), cell cycle arrest and suppression of cell migration and invasion. The mechanisms underlying the anti-metastasis effect of the D/D NPs involved downregulation of the expression of p-AKT, NF-κB and MMP-2. Therefore, D/D NPs represent a new nanoscale drug delivery system for treating metastatic breast cancer, responding to the acidic tumor microenvironment to release the chemotherapeutic drugs.

L-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid – and thermally activated – PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

Advanced colloidal technologies for the enhanced bioavailability of drugs

Bioavailability of the colloidal particles is of great concern. It is because about 40% of the newly discovered colloidal agents are poorly water soluble and thus poorly bioavailable. Various colloidal technologies have been adopted to enhance the bioavailability of such drugs. In this review, advanced colloidal technologies are discussed to understand the mechanism of bioavailability enhancement of drugs, coding latest references from the literature. Additionally, advantages and disadvantages of the concerned colloidal technologies are discussed to understand the potential usage of each process. All these colloidal technologies effectively enhance the bioavailability of poorly bioavailable drugs, either by protecting them from the environment of the gastrointestinal or by prolonging their intended therapeutic effect. Furthermore, complexation of the drug molecule with potential carries, particle size reduction to nanoscale, co-crystallization and self-emulsifying drug delivery system are also discussed which not only enhance the bioavailability but also reduce the potential toxicities of the loaded drugs. It is therefore important to understand the vital colloidal technologies with their recent advancements, potential applications and future challenges, which is discussed in this review. Finally, this article concludes that the advanced colloidal technologies, including freeze-dried liposome, solid lipid nanoparticle, polymeric nanoparticle (polymeric micelles), dendrimers and solid emulsifying drug delivery systems, have the potential to achieve improved bioavailability and targeted drug delivery.

Bortezomib-catechol conjugated prodrug micelles: combining bone targeting and aryl boronate-based pH-responsive drug release for cancer bone-metastasis therapy.

The treatment of metastatic tumors is highly desirable in clinics, which has also increased the interest in the design of nanoscale drug delivery systems. Bone metastasis is one of the most common pathways in the metastasis of breast cancer, and it is also an important cause for tumor recurrence and death. The aryl boronate group, as an acid-labile linker, has been introduced into nano-assemblies in recent years. Especially, as a proteasome inhibitor anticancer drug with a boric acid group, bortezomib can facilitate the formation of pH-sensitive aryl boric acid ester linkage with the catecholic group. In this study, bortezomib-loaded micelles with bone targeting properties were constructed for the treatment of breast cancer bone metastasis. The mixed micelles employed alendronate (ALN) as the bone-targeting ligand and encapsulated bortezomib-catechol conjugates as the cargo. In vitro and in vivo studies showed that compared with free drugs or control micelles, these prodrug micelles (ALN-NP) exhibited many favorable properties such as reduced systemic toxicity and improved therapeutic effects. Therefore, ALN-NP is promising as a nanovehicle for bone-targeting delivery of chemotherapeutic drugs. Furthermore, this study offers a novel strategy combining bone targeting and aryl boronate-based pH-responsive drug release for anti-metastasis therapy.

ZnO-based nanocarriers for drug delivery application: From passive to smart strategies

Due to the excellent biocompatibility as well as the low cost, nanoscale ZnO shows a great potential in drug delivery application. The richness of the structures, easy modification and pleasant properties of nanoscale ZnO make these materials reasonable choices for drug delivery. In the recent decade, various ZnO nanostructures as well as nanohybrids have been carried out for optimizational drug loading and carrying. To control the drug release behavior, many nanoscale ZnO-based smart drug delivery systems which are responsive to particular stimuli via characteristics of ZnO (e.g. dissolution in acid, microwave absorbing, hydrophobic/hydrophilic transition) have been successfully synthesized. Herein, we review the recent exciting progress on the nanoscale ZnO-based drug delivery systems: from the passive to smart strategies.

Targeted H+-Triggered Bubble-Generating Nanosystems for Effective Therapy in Cancer Cells

A novel targeting drug delivery system for cancer therapy based on H+-triggered bubble-generating nanosystems (BGNSs) was engineered. First, hollow mesoporous silica nanoparticles (HMSNs) were used to load doxorubicin (DOX). Then, the obtained drug-loaded HMSNs were treated with NaHCO3 to prepare the BGNSs. The BGNSs were coated with polydopamine (pDA), and finally, folic acids (FA) were anchored on the nanosystems to obtain the desired nanoscale drug delivery system (BGNSs@pDA-FA). BGNSs@pDA-FA was effectively internalized by cancer cells through folate receptor-mediated endocytosis and generated CO2 bubbles under the acidic environment of the lysosomes, thus enhancing lysosomal membrane permeability (LMP) to release caspase-3 into the cytoplasm, resulting in cancer cell death via an apoptosis-like pathway. Notably, we demonstrated that the BGNSs@pDA-FA exhibited a significant simultaneous synergetic cytotoxicity against MCF-7 cells and remarkably overcame the multidrug resistance (MDR) of MCF-7/ADR cells. Moreover, compared to free DOX and a nanosystem without FA modification (BGNSs), the BGNSs@pDA-FA induced relatively minor side effects in the MCF-10A cells. Therefore, the results showed that BGNSs@pDA-FA, as a targeted drug delivery system, have a good probability of overcoming the MDR of tumor cells with minor side effects on normal cells.

ID: 1044 DNA origami nanobot for sensitive drug delivery chemotherapy

The cutting-edge technology of constructing nanoscale objects using DNA origami has opened new directions for drug delivery in cancer chemotherapy research [1, 2]. This project aims to develop a novel DNA origami nanobot for drug delivery, with high selectivity and specificity for chemotherapy. It is important to be able to control the rate of drug release to maintain the concentration of chemotherapeutic agents at the desirable set-point [3]. This control can be achieved through various activation methods, similar to those used in liposome drug delivery systems, e.g. magnetism, radiation, ultrasound, heating etc. [4]. These stimuli can deliver specific types of energy (e.g. thermal), which can then activate a pre-designed nanobot- topology variation. For example, thermal energy can cause local DNA strands to melt and partially distort some local regions of the DNA topology, releasing drug molecules. One mechanism to activate the drug release is via radio frequency (RF) electromagnetic wave induced heating of gold nanoparticles [6]. A prototype nanobot will be developed and tested for heat-triggered nanobot switching between open and closed configurations. It is hypothesized that upon RF heating, the gold nanoparticles will concentrate the heat and cause the local DNA strands to melt, leading to the open configuration, without melting the rest of the nanobot structure. Heating time and power will be tuned to regulate the drug release rate. This work will develop an effective process control strategy for enhanced performance of nanoscale drug delivery systems.

Double-receptor-targeting multifunctional iron oxide nanoparticles drug delivery system for the treatment and imaging of prostate cancer.

As an alternative therapeutic treatment to reduce or eliminate the current side effects associated with advanced prostate cancer (PCa) chemotherapy, a multifunctional double-receptor-targeting iron oxide nanoparticles (IONPs) (luteinizing hormone-releasing hormone receptor [LHRH-R] peptide- and urokinase-type plasminogen activator receptor [uPAR] peptide-targeted iron oxide nanoparticles, LHRH-AE105-IONPs) drug delivery system was developed. Two tumor-targeting peptides guided this double-receptor-targeting nanoscale drug delivery system. These peptides targeted the LHRH-R and the uPAR on PCa cells. Dynamic light scattering showed an increase in the hydrodynamic size of the LHRH-AE105-IONPs in comparison to the non-targeted iron oxide nanoparticles (NT-IONPs). Surface analysis showed that there was a decrease in the zeta potential values for drug-loaded LHRH-AE105-IONPs compared to the NT-IONPs. Prussian blue staining demonstrated that the LHRH-AE105-IONPs were internalized efficiently by the human PCa cell line, PC-3. In vitro, magnetic resonance imaging (MRI) results confirmed the preferential binding and accumulation of LHRH-AE105-IONPs in PC-3 cells compared to normal prostate epithelial cells (RC77N/E). The results also showed that LHRH-AE105-IONPs significantly maintained T2 MRI contrast effects and reduced T2 values upon internalization by PC-3 cells. These paclitaxel-loaded double-receptor-targeting IONPs also showed an approximately twofold reduction in PC-3 cell viability compared to NT-IONPs.

Construction of a Supramolecular Drug-Drug Delivery System for Non-Small-Cell Lung Cancer Therapy.

Nanoscale drug delivery systems (DDSs) are generally considered to be an effective alternative to small molecular chemotherapeutics due to improved accumulation in the tumor site and enhanced retention in blood. Nevertheless, most DDSs have low loading efficiency or even pose a high threat to normal organs from severe side effects. Ideally, a supramolecular drug-drug delivery system (SDDDS) composed of pure drugs via supramolecular interaction provides a hopeful approach for cancer treatment. Herein we propose a facile method to construct SDDDS via coassembly of gefitinib (GEF) and tripeptide tyroservatide (YSV), two kinds of chemotherapeutic pharmaceuticals for non-small-cell lung cancer (NSCLC) via multiple intermolecular interactions, including hydrogen bonding and π-π stacking. As shown through transmission electron microscopy (TEM) and dynamic light scattering (DLS), GEF and YSV self-assemble into nanoparticles with regular morphology and uniform size, which facilitates the delivery of both drugs. In vitro studies demonstrate that the SDDDS is much more efficient in entering cancer cells and inhibiting the proliferation of cancer cells compared with single GEF, YSV, or GEF/YSV drug mixture. In vivo experiments show that the SDDDS can selectively accumulate in tumor tissue, resulting in much better drug efficacy without evident side effects. Considering the advantages of the SDDDS, we believe this strategy provides a promising route for enhanced anticancer therapy in nanomedicine.