Selective Drug Release Research Articles

ATP-triggered anticancer drug delivery

Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

PH-controllable drug carrier with SERS activity for targeting cancer cells

A type of pH-controllable drug carrier is demonstrated based on mesoporous silica nanoparticles and chitosan/poly (methacrylic acid), which can simultaneously serve as the surface enhanced Raman scattering (SERS) traceable drug carriers for targeting cancer cells. The pH-sensitive releasing characteristics can be achieved by coating the nanoparticles with a layer of chitosan/poly (methacrylic acid) (CS-PMAA), while strong SERS signals can be obtained from the SERS reporter tagged Ag nanoparticles in the core. Our experimental results show that doxorubicin (DOX) was effectively encapsulated into the nanocarriers and can be released in response to the ambient pH value. Specifically, an increased amount of DOX release was observed at lower pH value. In addition, the composite nanoparticles were conjugated with transferrin (Tf) to target transferrin receptor (TfR)-overexpressed cancer cells. The targeting ability as well as the intracellular location of the drug carrier was investigated through SERS mapping while the distribution of DOX was monitored by fluorescence images. The results show that the demonstrated drug carrier can simultaneously fulfill the functionalities of pH-responsive drug release, SERS-traceable characteristics and cancer cells targeting, which has a unique potential for the pH-controllable drug delivery nanosystems.

PH-Responsive and near-infrared-emissive polymer nanoparticles for simultaneous delivery, release, and fluorescence tracking of doxorubicin in vivo

Dextran modified with pendant acetals is used to load doxorubicin (DOX) and a near-infrared-emissive conjugated polymer (BTTPF), and this aims to provide selective drug release at therapeutic targets including tumors. The BTTPF is applicable to tracking the anticancer drug release through the change of Förster resonance energy transfer efficiency between doxorubicin and BTTPF during degradation of the nanoparticles in vivo.

Protamine‐Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release

The fabrication of a mesoporous silica nanoparticle (MSN)−protamine hybrid system (MSN−PRM) is reported that selectively releases drugs in the presence of specific enzyme triggers present in the proximity of cancer cells. The enzyme trigger involved is a protease called trypsin, which is overexpressed in certain specific pathological conditions, such as inflammation and cancer. Overexpression of trypsin is known to be associated with invasion, metastasis, and growth in several cancers, such as leukemia, colon cancer, and colorectal cancer. The current system (MSN–PRM) consists of an MSN support in which mesopores are capped with an FDA‐approved peptide drug protamine, which effectively blocks the outward diffusion of the drug molecules from the mesopores of the MSNs. On exposure to the enzyme trigger, the protamine cap disintegrates, opening up the molecular gates and releasing the entrapped drug molecules. The system exhibits minimal premature release in the absence of the trigger and selectively releases the encapsulated drugs in the presence of the proteases secreted by colorectal cancer cells. The ability of the MSN–PRM particles to deliver anticancer drugs to colorectal cancer cells has also been demonstrated. The hydrophobic drug is released into cancer cells subsequent to disintegration of the protamine cap, resulting in cell death. Drug‐induced cell death in colorectal cancer cells is significantly enhanced when the hydrophobic drug that is known to degrade in aqueous environments is encapsulated in the MSN–PRM system in comparison to the free drug (P < 0.05). The system, which shows good biocompatibility and selective drug release, is a promising platform for cancer specific drug delivery.

Evaluation of a reductively activated duocarmycin prodrug against murine and human solid cancers

In treating cancer with clinically approved chemotherapies, the high systemic toxicity and lack of selectivity for malignant cells often result in an overall poor response rate. One pharmacological approach to improve patient response is to design targeted therapies that exploit the cancer milieu by reductively activating prodrugs, which results in the selective release of the free drug in the tumor tissue. Previously, we characterized prodrugs of seco-CBI-indole2 (CBI-indole2) designed to be activated in hypoxic tumor microenvironments, wherein the tumor maintains higher concentrations of “reducing” nucleophiles capable of preferentially releasing the free drug by nucleophilic attack on a weak N-O bond. Of these prodrugs, BocNHO-CBI-indole2 (BocNHO) surpassed the efficacy of the free drug, CBI-indole2, when examined in vivo in the murine L1210 leukemia model and demonstrated reduced toxicity suggesting a targeted or sustained release in vivo. Herein, we further examine the biological activity of the BocNHO prodrug in murine breast cancer, as well as human prostate and lung cancer cell lines, in vitro. Notably, BocNHO manifests potent antiproliferative and cytotoxic activity in all three tumor cell lines. However, in comparison to the activity observed in the murine cancer cell line, the human cancer cell lines were less sensitive, especially at early timepoints for cytotoxicity. Based on these findings, BocNHO was tested in a more clinically relevant orthotopic lung tumor model, revealing significant efficacy and reduced toxicity compared with the free drug. The data suggests that this pharmacological approach to designing targeted therapies is amenable to human solid tumors.

Simultaneous analysis of non-steroidal anti-inflammatory drugs using electrochemically controlled solid-phase microextraction based on nanostructure molecularly imprinted polypyrrole film coupled to ion mobility spectrometry

A simple, rapid, and highly sensitive method for simultaneous analysis of anti-inflammatory drugs (naproxen, ibuprofen, and mefenamic acid) in diluted human serum was developed using the electrochemically controlled solid-phase microextraction coupled to ion mobility spectrometry. A conducting molecularly imprinted polymer film based on polypyrrole was synthesized for the selective uptake and release of drugs. The film was prepared by incorporation of a template molecule (naproxen) during the electropolymerization of pyrrole onto a platinum electrode using cyclic voltammetry method. The measured ion mobility spectrometry intensity was related to the concentration of analytes taken up into the films. The calibration graphs (naproxen, ibuprofen, and mefenamic acid) were linear in the range of 0.1-30 ng/mL and detection limits were 0.07-0.37 ng/mL and relative standard deviation was lower than 6%. On the basis of the results obtained in this work, the conducting molecularly imprinted polymer films as absorbent have been applied in the electrochemically controlled solid-phase microextraction and ion mobility spectrometry system for the selective clean-up and quantification of trace amounts of anti-inflammatory drugs in human serum samples. Scanning electron microscopy has confirmed the nano-structure morphology of the polypyrrole film.

NIR Photoresponsive Crosslinked Upconverting Nanocarriers Toward Selective Intracellular Drug Release

An NIR-responsive mesoporous silica coated upconverting nanoparticle (UCNP) conjugate is developed for controllable drug delivery and fluorescence imaging in living cells. In this work, antitumor drug doxorubicin (Dox) molecules are encapsulated within cross-linked photocaged mesoporous silica coated UCNPs. Upon 980 nm light irradiation, Dox could be selectively released through the photocleavage of theo-nitrobenzyl (NB) caged linker by the converted UV emission from UCNPs. This NIR light-responsive nanoparticle conjugate demonstrates high efficiency for the controlled release of the drug in cancer cells. Upon functionalization of the nanocarrier with folic acid (FA), this photocaged FA-conjugated silica-UCNP nanocarrier will also allow targeted intracellular drug delivery and selective fluorescence imaging towards the cell lines with high level expression of folate receptor (FR).

Dual Targeting of Hypoxic and Acidic Tumor Environments with a Cobalt(III) Chaperone Complex

The rational design of prodrugs for selective accumulation and activation in tumor microenvironments is one of the most promising strategies for minimizing the toxicity of anticancer drugs. Manipulation of the charge of the prodrug represents a potential mechanism to selectively deliver the prodrug to the acidic tumor microenvironment. Here we present delivery of a fluorescent coumarin using a cobalt(III) chaperone to target hypoxic regions, and charged ligands for pH selectivity. Protonation or deprotonation of the complexes over a physiologically relevant pH range resulted in pH dependent accumulation of the fluorophore in colon cancer cells. Furthermore, in a spheroid solid tumor model, the anionic complexes exhibited preferential release of the fluorophore in the acidic/hypoxic region. By fine-tuning the physicochemical properties of the cobalt-chaperone moiety, we have demonstrated selective drug release in the acidic and hypoxic tumor microenvironment.

Abstract B50: Per oral nanogel conjugates of activated nucleoside analogs are effective in the treatment of drug-resistant tumors

Abstract Purpose: Chemotherapeutic application of cytotoxic nucleoside analogs and bases resulted in the development of specific mechanisms of drug resistance. Numerous attempts to develop phosphorylated prodrugs of nucleoside analogs effective in vivo have not yet yielded clinical drugs. On the other hand, there exist a very limited list of oral anticancer drugs despite of the fact that per oral administration remains a preferred route of administration due to its convenience and better patient compliancy. Recently, we developed novel conjugates of biocompatible polymers and phosphorylated nucleoside analogs, which fold into small nanogel particles in aqueous media and show an enhanced activity against aggressive and drug-resistant tumor cells. These nanogel-drug conjugates are stable in conditions existing in the gastrointestinal tract, but can release activated drug molecules after internalization and enzymatic hydrolysis in cancer cells. Method: Poly(vinyl alcohol), a nontoxic biocompatible polymer, having excellent mucoadhesive properties that are important for gastrointestinal (GI) absorption, was decorated with cholesterol moieties(CPVA) and conjugated with floxuridine(FU) and N-acylated gemcitabine(Gem) via a tetraphosphorylated linker. These CPVA-drug conjugates formed compact nanogels (20-60 nm in diameter) in aqueous media. Drug content in the conjugates was usually 8–12%. We examined cytotoxicity of the nanogel-drug conjugates in human breast, prostate and drug-resistant pancreatic cancer, leukemic and lymphoma cells. Tumor growth inhibition was evaluated in s.c. xenograft animal models following the administration of nanogel-drug conjugates peritumorally or orally, for example, by liquid gavage or with drinking water ad libitum. Results: The hydrophobic modification by cholesterol moieties played a significant part in the intracellular drug accumulation due to higher cytotoxic activity. In most cases, the nanogel-drug conjugates demonstrated a 3- to 30-fold higher efficacy than nucleoside analogs showing both cytotoxic and cytostatic activities. We found selective drug release patterns depending on the environmental pH and tissue-related enzymatic activities. Importantly, these conjugates were stable at low pH and, therefore, could be administered orally. High viscosity of nanogel-drug conjugate solutions is also a positive factor increasing their absorption in GI tract and providing a depot-like pattern of drug release after s.c. injections. Due to the molecular mass of nanogel-drug conjugates (>50 kDa), absorbed drug nanoformulations can potentially be retained in tumors via leaking neovasculature due to the enhanced permeability and retention effect. In all experiments, we observed sustained antitumor effects at relatively low drug doses compared to control groups and no chronic toxicity or weight loss was detected. Conclusion: Nanogel drug conjugates demonstrated advanced accumulation and drug release profiles during the treatment of cancer cells resistant to nucleoside analogs and displayed a strong growth inhibition of drug-resistant tumors in xenograft animal models following per oral administration. Therefore, nanogel drug conjugates constitute a novel efficient formulation for the treatment of drug resistant aggressive cancers. Acknowledgements: The National Cancer Institute's support CA136921 (for S.V.V.) is greatly appreciated.

Folate-targeting magnetic core–shell nanocarriers for selective drug release and imaging

One of the most urgent medical requirements for cancer diagnosis and treatment is how to construct a multifunctional vesicle for simultaneous diagnostic imaging and therapeutic applications. In our study, superparamagnetic iron oxide nanocrystals (SPIONs) and doxorubicin hydrochloride (DOX) are co-encapsulated into PLGA/polymeric liposome core–shell nanocarriers for achieving simultaneous magnetic resonance imaging and targeting drug delivery. The core–shell nanocarrier was self-assembled from a hydrophobic PLGA core and a hydrophilic folate coated PEGlated lipid shell. The experiment showed that folate-targeting magnetic core–shell nanocarriers show clear core–shell structure, excellent magnetism and controlled drug release behavior. Importantly, the core–shell nanoparticles achieve the possibility of co-delivering drugs and SPIONs to the same cells for enhancing magnetic resonance imaging (MRI) effect and improving drug delivery efficiency simultaneously. Our data suggests that the folate-targeting magnetic core–shell nanocarriers (FMNs) could provide effective cancer-targeting and MRI as well as drug delivery. The FMNs may become a useful nanomedical carrier system for cancer diagnosis and treatment.

ChemInform Abstract: A Novel pH‐Sensitive (.+‐.)‐α‐Tocopherol‐5‐fluorouracil Adduct with Antioxidant and Anticancer Properties

Abstractsynthesis and utilization of title compound (I) for selective drug release in the stomach

A selective drug-release system consisting of surface-modified electrospun carbon fibers by oxy/fluorination

A selective drug-release system was prepared for a controlled drug release between hydrophobic and hydrophilic drugs by using a prepared membrane. A membrane was constructed by electrospun carbon fibers. A porous structure was created in the carbon fibers by chemical activation to reduce the initial drug-burst phenomenon by drug storage in the pores. The surface of the activated carbon fibers was modified by the addition of hydrophobic/hydrophilic functional groups by oxyfluorination or fluorination treatments to allow the selective release of mixed hydrophobic and hydrophilic drugs. The in vitro drug permeation was studied under various applied electric voltages. The initial drug-release phenomenon was reduced due to the storage effect by the improved pore structure, and the drug-release rate was controlled by the intensity of the applied electric voltage. In addition, selective drug release was observed with the presence of the hydrophobic or hydrophilic functional groups introduced through oxyfluorination or fluorination treatments.

Selective Recognition of Co‐assembled Thrombin Aptamer and Docetaxel on Mesoporous Silica Nanoparticles against Tumor Cell Proliferation

Generally, tumor development relies on the material, energy, signal transduction in the extracellular matrix and intracellular environment. An optimal systematic approach for cancer treatment can cut off the connection between the tumor cell and extracellular matrix and inhibit the intracellular activity. The combination of two or more therapeutic approaches can cooperatively promote tumor suppression and is a very effective strategy for synergistic or combined anticancer treatment. Recent attention has been devoted to the engineering of specialized vehicles that encapsulate traditional chemotherapeutic drugs for stimuli-responsive release, and the targeting of these vehicles to tumor cells with highly efficient ligands that selectively recognize tumor-associated or tumor-specific antigens. It has been found that nanoscale vehicles can offer prolonged circulation times and selective binding to cancer tissues through enhanced permeation and retention effects. Importantly, the size of these nanocarriers, in contrast to single molecules, allows them to provide a larger drug payload and to achieve higher targeting specificity. A wide variety of targeting molecules have been synthesized or separated for use in cancer therapy, including peptides, oligosaccharides or humanized antibodies. Interestingly, nucleic acid ligands, also called aptamers, have been developed as a novel class of targeting molecules for therapeutic and diagnostic applications. Aptamers are single-stranded DNA or RNA oligonucleotides that can fold by intramolecular interaction into specific three-dimensional conformations to recognize various kinds of targets with high affinity and specificity. As the first selected aptamer, 15-mer thrombin binding aptamer (TBA), which can fold into a compact intramolecular tetraplex with an antiparallel orientation of strands in the chair-like conformation, inhibits the enzymatic function of thrombin. The significant neoplastic biological effect of thrombin involves clotting-dependent mechanism and protease-activated receptor-1 (PAR-1) related signaling; this leads to several tumor functions, specifically proliferation and angiogenesis. To the best of our knowledge, although a considerable amount of research has been carried out to exploit TBA in the construction of biosensors, molecular machines, and anticoagulants, 32] little has been done to employ TBA to target thrombin for disturbing fibrin formation and suppressing tumor cell growth by restraining the unique proteolytic ability of thrombin and further breaking related signal transduction pathways. Here, we report a TBA-tethered lipid-coated mesoporous silica nanoparticle (TBA–lipid–MSN) hybrid as an extraand intracellular anticancer nanocarrier. A potent anticancer drug, docetaxel (Dtxl), was incorporated into this hybrid system. Selective recognition and drug release were demonstrated by using this co-assembled delivery platform (Scheme 1). Briefly, the modified thrombin binding aptamer, 5’-GGTTG GTGTG GTTGG AAAAA AAAAA AAAAA-C18-spacer-3 (TBAA15-C18) was reconstituted into hydrogenated soybean phosphatidylcholine (HSPC), mPEG2000–distearoylphosphatidylethanolamine (mPEG2000–DSPE) and docetaxel containing mixed lipid vesicles. The obtained vesicles were spread on the outer surface of MSNs, which were synthesized by a base-catalyzed sol-gel method. Introduction of MSN cores is helpful to improve the mechanical stability of aptamer–liposome conjugation. The final formulation obtained was 1 mg TBAA15– lipid–Dtxl–MSN with 3 nmol Dtxl and about 0.44 nmol TBAA15. After TBAA15–lipid–Dtxl–MSN were co-cultured with HeLa cells and thrombin, the co-assembled bioconjugates were expected to not only suppress cell growth in the extracellular matrix based on the specific antithrombin characteristics of the aptamer by disturbing PAR-1 receptor signaling, but also to achieve a much more effective cytotoxicity in the cytoplasm because of the contribution of Dtxl. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed to examine the self-assembly of the TBAA15–lipid–Dtxl–MSN bioconjugates. The monodispersed short, rod-shaped MSNs with a diameter of 100–200 nm and aspect ratio of about 2, are shown in Figure S1A in the Supporting Information. The [a] L. Gao, Dr. Y. Cui, Dr. J. Fei, Prof. Dr. J. Li Beijing National Laboratory for Molecular Sciences Key Laboratory of Colloid and Interface Science Center for Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Zhong Guan Cun Beijing, 100190 (P.R. China) Fax: (+86)10-8261-4087 E-mail : jbli@iccas.ac.cn [b] Prof. Dr. Q. He Micro/Nano Technology Research Centre Harbin Institute of Technology, Harbin, 150080 (P.R. China) [c] Dr. Y. Yang National Center for Nanoscicence and Technology No. 11, Bei Yi Tiao, Zhong Guan Cun, Beijing, 100190 (P.R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101658.

Abstract 2831: Novel antibody-drug conjugates for selective tumor activation

Abstract Auristatin based antibody-drug conjugates (ADCs) have demonstrated profound activites, both preclinically and clinically. Upon internalization, the active auristatin is released through proteolytic degradation of the linker, where it induces cell kill through the inhibition of tubulin polymerization. Once released from the antibody, clearance of the auristatin proceeds via the hepatobiliary route. This finding prompted us to explore new auristatin-peptide drug linkers that had the capacity to release the active form of the drug in tumors, but an inactive form in the liver. To this end, we designed a novel in vivo screen in which multiple ADCs were cassette dosed in mice. LC-MS/MS was used to determine which sequences amongst approximately 800 new auristatin-peptide derivatives allowed for differential drug activation. Sequences were identified that allowed for more selective intratumoral release of the active drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2831. doi:10.1158/1538-7445.AM2011-2831

Biodegradable polymeric microcapsules for selective ultrasound-triggered drug release

A series of hollow biodegradable polymeric microcapsules were prepared, of which their susceptibility to ultrasound was used for triggered release. High speed imaging of the ultrasound experiments showed a strong correlation between the acoustic pressure needed to activate these microcapsules and their shell thickness to diameter ratio. Based on this information a selective triggering of capsules with two different shell thickness to diameter ratios was successfully performed. The capsules were mixed in a single system and were activated independently from each other by a differentiation in acoustic pressure levels. This application is of great interest in the field of drug delivery, since this system allows for localized multiple drug releases in a selective fashion.

A novel pH-sensitive (±)-α-tocopherol–5-fluorouracil adduct with antioxidant and anticancer properties

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil (VE-5-FU) adduct with antioxidant and anticancer properties for antioxidant-based cancer chemoprevention was synthesized and utilized for selective drug release in the stomach.

Development of polymeric and cyclodextrin nanoparticles for camptothecin delivery

Cell-selective drug release in the central nervous system (CNS) holds great promise for the treatment of many CNS disorders but it is still challenging. We previously demonstrated that polymeric nanoparticles (NPs) injected intra-parenchyma in the CNS can be internalized specifically in microglia/macrophages surrounding the injection site. Here, we explored NPs administration in the cerebrospinal fluid (CSF) to achieve a wider spreading and increased cell targeting throughout the CNS; we generated new NPs variants and studied the effect of modifying size and surface charge on NPs biodistribution and cellular uptake. Intra-cerebroventricular administration resulted in prevalent localization of the NPs in proximity to stem-cell niches, such as around the lateral ventricles, the subventricular zone and the rostral migratory stream. NPs internalization occurred preferentially in brain myeloid cells/microglia. We demonstrated that brain biodistribution and extent of internalization in microglia are influenced by NPs dimensions and can be improved by applying a transient disruption of the blood-brain barrier with mannitol, leading to NPs internalization in up to 25% of brain myeloid/microglia cells. A fraction of the targeted cells was positive for markers of proliferation or stained positive for stemness/progenitor-cell markers such as Nestin, c-kit, or NG2. Interestingly, through these newly formulated NPs we obtained controlled and selective release of drugs otherwise difficult to formulate (such as busulfan and etoposide) to the target cells, preventing unwanted side effects and the toxicity obtained by direct brain delivery of the not encapsulated drugs. Overall, these data provide proof of concept of the applicability of these novel NP-based drug formulations for achieving internalization not only in mature microglia but also possibly in more immature myeloid cells in the brain and pave the way for brain-restricted microglia-targeted drug delivery regimens.

CE‐ESI‐MS/MS as a rapid screening tool for the comparison of protein–ligand interactions

In drug development, the combinatorial synthesis of drug libraries is common use, therefore efficient tools for the characterization of drug candidates and the extent of interaction between a drug and its target protein is a central question of analytical interest. While biological activity is tested today by enzyme assays, MS techniques attract more and more attention as an alternative for a rapid comparison of drug-target interactions. CE enables the separation of proteins and drug-enzyme complexes preserving their physiological activity in aqueous media. By hyphenating CE with ESI-MS/MS, the binding strength of enzyme inhibitors can be deduced from MS/MS experiments, which selectively release the inhibitor from the drug-target complex after CID. In this study, alpha-chymotrypsin (CT), a serine protease, was chosen as a model compound. Chymostatin is a naturally occurring peptide aldehyde binding to CT through a hemiacetal bond and electrostatic interaction. First, a CE separation was developed, which allows the analysis of alpha-CT and a chymotrypsin-chymostatin complex under MS-compatible conditions. The use of neutral-coated CE capillaries was mandatory to reduce analyte-wall interactions. ESI-quadrupole ion trap-MS was worked out to demonstrate the selective drug release after CID. Fragmentation of the drug-enzyme complex was monitored in dependence from the excitation energy in the ion trap, leading to the V(50) voltage that enables 50% complex fragmentation as a reference value for chymotrypsin-chymostatin complex. A stable CE-ESI-MS/MS setup was established, which preserves the drug-enzyme complexes during ionization-desolvation processes. With this optimized setup, different CT inhibitors could be investigated and compared.

A pH-sensitive graphene oxide composite hydrogel

Graphene oxide/poly(vinyl alcohol) (GO/PVA) composite hydrogel was prepared and utilized for selective drug release at physiological pH.

Curcumin Loaded pH-Sensitive Nanoparticles for the Treatment of Colon Cancer

The investigation was aimed at designing pH-sensitive, polymeric nanoparticles of curcumin, a natural anti-cancer agent, for the treatment of colon cancer. The objective was to enhance the bioavailability of curcumin, simultaneously reducing the required dose through selective targeting to colon. Eudragit S100 was chosen to aid targeting since the polymer dissolves at colonic pH to result in selective colonic release of the entrapped drug. Solvent emulsion-evaporation technique was employed to formulate the nanoparticles. Various process parameters were optimized and the optimized formulation was evaluated for particle size distribution and encapsulation efficiency before subjecting to freeze-drying. The freeze dried product was characterized for particle size, drug content, DSC studies, particle morphology. Anti-cancer potential of the formulation was demonstrated by MTT assay in HT-29 cell line. Nanometric, homogeneous, spherical particles were obtained with encapsulation efficiency of 72%. Freeze-dried nanoparticles exhibited a negative surface charge, drug content of > 99% and presence of drug in amorphous form which may result in possible enhanced absorption. MTT assay demonstrated almost double inhibition of the cancerous cells by nanoparticles, as compared to curcumin alone, at the concentrations tested. Enhanced action may be attributed to size influenced improved cellular uptake, and may result in reduction of overall dose requirement. Results indicate the potential for in vivo studies to establish the clinical application of the formulation.