Conjugation Of Curcumin Research Articles

Toxicity assessment of silica nanoparticles, and their conjugates with curcumin on Drosophila melanogaster

We synthesized silica nanoparticles by using a straightforward chemical method. UV–VIS spectroscopy confirmed the primary characterization of curcumin (CU), silica nanoparticles (SiNPs) and conjugation of curcumin-silica nanoparticles (CU-SiNPs) at 420 nm, 337 nm and 417 nm, respectively. FTIR indicated the presence of diarylheptanoids chromophore group on curcumin and curcumin-silica nanoparticles conjugate, which confirms successfull conjugation. Curcumin indicated several distinct peaks in XRD micrograph due to its crystalline nature, whereas silica nanoparticles showed typical amorphous pattern. The average particle size of synthesized SiNPs and CU-SiNPs were 10 nm and 15 nm, respectively. It was observed that curcumin crystallinity was retained in CU-SiNPs conjugate. Drosophila melanogaster was used to assess the level of toxicity that can be associated with curcumin, silica nanoparticles and their conjugates on life-history traits, fertility, hatchability and development time. In all experimental set, the range of eggs/fly/day 61–63 was comparable in experimental as well as control set of flies at 10 mg L-1 doses. Furthermore, the control sample showed 100% hatchability, whereas the experimental group showed 99–100% hatchability. Overall, curcumin, nanoparticles and their conjugates, showed high bioavailability along with no significant toxicity

CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells

Acute myeloblastic leukemia (AML) is a disease with a high rate of relapse and drug resistance due to the remaining leukemic stem cells (LSCs). Therefore, LSCs are specific targets for the treatment of leukemia. CD123 is specifically expressed on LSCs and performs as a specific marker. Curcumin is the main active compound of a natural product with low toxicity for humans. It has been reported to inhibit leukemic cell growth. However, curcumin is practically insoluble in water and has low bioavailability. In this study, we aimed to formulate curcumin nanoparticles and conjugate with the anti-CD123 to overcome the low water solubility and improve the targeting of LSCs. The cytotoxicity of both curcumin-loaded PLGA/poloxamer nanoparticles (Cur-NPs) and anti-CD123-curcumin-loaded PLGA/poloxamer nanoparticles (anti-CD123-Cur-NPs) were examined in KG-1a cells. The results showed that Cur-NPs and Cur-NPs-CD123 exhibited cytotoxic effects on KG-1a cells with the IC50 values of 74.20 ± 6.71 and 41.45 ± 5.49 µM, respectively. Moreover, anti-CD123-Cur-NPs induced higher apoptosis than Cur-NPs. The higher uptake of anti-CD123-Cur-NPs in KG-1a cells was confirmed by using flow cytometry. In conclusion, the anti-CD123-Cur-NPs formulation improved curcumin’s bioavailability and specific targeting of LSCs, suggesting that it is a promising drug delivery system for improving the therapeutic efficacy against AML.

Conjugation of curcumin with Ag nanoparticle for improving its bioavailability and study of the bioimaging response

Conjugation of curcumin with Ag nanoparticle for improving its bioavailability and study of the bioimaging response

Correction to: Degree-based entropy of molecular structure of hyaluronic acid–curcumin conjugates

Correction to: Degree-based entropy of molecular structure of hyaluronic acid–curcumin conjugates

Surface conjugation of curcumin with self-assembled lysozyme nanoparticle enhanced its bioavailability and therapeutic efficacy in multiple cancer cells

Here, we prepared nano self-assembly of lysozyme via a directed optimized desolvation process and conjugated it with an anticancer natural polyphenol, curcumin (Cur) onto the surface via chemical crosslinking. When lysozyme nano-assembly was surface conjugated with curcumin (SNLYZ-Cur) and evaluated against pathogenic cells, it showed excellent antimicrobial as well as anticancer activity compared to their individual effects (SNLYZ and curcumin). Moreover, its antioxidant property was also observed to be remarkably enhanced than its individual component. The mean size of SNLYZ and SNLYZ-Cur was estimated to be ~75 and ~120 nm, respectively. From disc-diffusion and time-kill assay, it was confirmed that SNLYZ–Cur has an enhanced antimicrobial effect over its Cur alone. Similarly, SNLYZ–Cur was also demonstrated better antioxidant potential than free Cur as well as SNLYZ. The nano conjugate, SNLYZ–Cur showed great potential as an anticancer agent in the multiple cancer types (HeLa, MCF-7, MDAMB-231 and MG 63) which was too found enhanced over SNLYZ and free Cur. We further proved that the anticancer activity can be enhanced by attaching Folate-receptor (FR) based targeting. Hence, SNLYZ-Cur nanoconjugate having enhanced antibacterial, antioxidant, and anticancer activity, might be used as a promising bioactive pharmaceutical therapeutic agent in multiple diseases including cancer.

Iron oxide nanoparticles conjugated curcumin to promote high therapeutic efficacy of curcumin against hepatocellular carcinoma

BackgroundCurcumin’s excellent conjugation capability with iron oxide nanoparticles plays a crucial role in enhancing both properties. Iron oxide, as a nanocarrier, will improve curcumin anticancer activity, while curcumin, as a capping agent, will minimize iron oxide nanoparticles toxicity and optimize their biomedical use. MethodologyCytotoxic and antioxidant effects of free curcumin (free Cur) and curcumin capped iron oxide nanoparticles (IONs@Cur) against human liver cancer cells (HepG2) were investigated in vitro. The genomic effect of free Cur and IONs@Cur on the expression of tumor suppressor gene (TP53), autophagy 4 (ATG-4), and superoxide dismutase (SOD2) genes were assessed using quantitative PCR (qPCR). ResultsIONs@Cur results showed significant cytotoxic effects against HepG2 cells, compared with free Cur, and the measured total antioxidant capacity (TAC) for HepG2 cells treated with IONs@Cur was superior to free Cur. Additionally, the treatment with IONs@Cur significantly upregulated the gene expression levels of SOD2 and TP53. Remarkably, the immunofluorescence staining of ATG-4 demonstrated that curcumin conjugation with IONs potentiated the cancer killing effect of curcumin via inducing autophagy. ConclusionThe promising iron oxide nanocarrier would greatly enhance curcumin anticancer activities against HepG2 cells.

Degree-based entropy of molecular structure of hyaluronic acid–curcumin conjugates

The graph entropy is an important quantity of information theory. It measures the structural information of chemical graphs and complex networks. The graph entropy measures have specific chemical applications in discrete mathematics, biology and chemistry. The main contribution of this paper is to study properties of graph entropies and then goes on to discuss the structure of hyaluronic acid (HA)–curcumin conjugates. Also we compute entropies of this structure by using certain degree-based topological indices with the help of information function.

A comparison of the location in membranes of curcumin and curcumin-derived bivalent compounds with potential neuroprotective capacity for Alzheimer’s disease

Curcumin and two bivalent compounds, namely 17MD and 21MO, both obtained by conjugation of curcumin with a steroid molecule that acts as a membrane anchor, were comparatively studied. When incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine the compounds showed a very limited solubility in the model membranes. Curcumin and the two bivalent compounds were also incorporated in membranes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and quenching the fluorescence of pure curcumin or of the curcumin moiety in the bivalent compounds by acrylamide it was seen that curcumin was accessible to this water soluble quencher but the molecule was somehow located in a hydrophobic environment. This was confirmed by quenching with doxyl-phosphatidylcholines, indicating that the curcumin moieties of 17MD and 21MO were in a more polar environment than pure curcumin itself. 1H NOESY MAS-NMR analysis supports this notion by showing that the orientation of curcumin was parallel to the plane of the membrane surface close to C2 and C3 of the fatty acyl chains, while the curcumin moiety of 17MD and 21MO positioned close to the polar part of the membrane with the steroid moiety in the centre of the membrane. Molecular dynamics studies were in close agreement with the experimental results with respect to the likely proximity of the protons studied by NMR and show that 17MD and 21MO have a clear tendency to aggregate in a fluid membrane. The anchorage of the bivalent compounds to the membrane leaving the curcumin moiety near the polar part may be very important to facilitate the bioactivity of the curcumin moiety when used as anti-Alzheimer drugs.

PH-sensitive curcumin conjugated micelles for tumor triggered drug delivery

Development of new drugs are confronted with some barriers and challenges, since these projects are mainly expensive, complex, time consuming with lack of success, there is an urgent need to reformulate the current poorly water soluble anti-cancer drugs. In this study, a new type of polymer–curcumin conjugates based on glycidyl azide polymer (GAP) was developed for cancer therapy. The copolymer was used for delivery of curcumin (CUR) as an anticancer drug to cancer cells. Our method is based on the facile conjugation of CUR to amine-containing polymeric vehicles through imine linkage bonds, which could remain stable in normal physiological condition while readily dissociate by an acidic environment and make the prodrug active to liberate its payload CUR to inhibit cell growth. The results demonstrated that fabricated amphiphilic PDCs were self-assembled into nanosized micelles in aqueous solution and the micelles showed an average size of 180 nm with a good polydispersity index. Drug release studies demonstrated that this nano-conjugate is fairly stable at physiologic environments but prone to mild acidic conditions which would trigger the release of conjugated CUR. Moreover, the PDCs micelles exhibited excellent cytotoxicity effect on 4T1 mouse breast cancer cell line but no significant toxicity was observed for the copolymer. In addition, the copolymer did not display remarkable toxicity against A. salina even at high doses of copolymer. In addition, the synthesized PDCs exhibited hemolysis lowers than 6%. The safety of copolymers as a drug vehicle was also confirmed by LD50, since all mice which treated with 5000 mg/Kg (limited dose) were still alive after one week. Our findings revealed that these unique pH-sensitive PDCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.

Nanotized curcumin-benzothiophene conjugate: A potential combination for treatment of cerebral malaria.

The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone. Herein, we formulated nanotized conjugate of curcumin and compound 6 (cur-compound 6) in the size range of 30-90 nm as observed via TEM, AFM and DLS analysis in the study. The nanotized preparation was found to be readily dispersible in water, physically and chemically stable and exhibited sustained release profile of both curcumin and compound 6 till 48 hr. Treatment of P. falciparum parasites with the nanotized conjugate for 24 hr resulted in rapid clearance of the parasites. Furthermore, P. berghei infected mice treated with nanotized conjugate formulation survived till 90 days with complete eradication of the parasites from RBC. This improved efficacy of the nanotized formulation was possible because of the increased absorption of the compounds via oral administration owing to enhanced dispersibility of the formulation in aqueous medium. Moreover, an improved oral bioavailability of the nanotized formulation lowered the dosage at which the pharmacological effect was achieved while avoiding any observable adverse harmful side effects.

Curcumin and isonicotinic acid hydrazide functionalized gold nanoparticles for selective anticancer action

Besides physicochemical properties, careful design of biomolecular surface corona can dictate therapeutic potential of nanoparticles. Therefore, we demonstrate a new approach to improve the anticancer potential of gold nanoparticles (AuNPs) by developing a strong corona of curcumin and isonicotinic acid hydrazide (INH) around them. Here, curcumin reduced AuNPsCur are surface-functionalized with biologically active INH (AuNPsCur@INH). Our investigations on human lung squamous carcinoma (LK-2) and human lung fibroblast (TIG-120) cells indicate selective toxicity of functionalized nanoparticles. Conjugation of curcumin and INH on the surface of AuNPs induced anticancer action through reactive oxygen species (ROS) generation. The further extension of this study revealed apoptosis and morphological changes in LK-2 and TIG-120 cells, respectively. Moreover, the anticancer potential of these nanoparticles is compared with standard cisplatin. The outcomes of the work determine that the facile functional surfaces on nanoparticles can be important in controlling the biological activities of nanoparticles.

Abstract 6362: TH1901, a novel curcumin-peptide conjugate for the treatment of Sortilin-positive (SORT1+) cancer

Abstract Rational: Phytochemicals are compounds found in plant foods that can help prevent the occurrence of chronic diseases like cancer. Several studies, over the last decade on the impact of phytochemicals in cancer treatment, have provided experimental evidence that curcumin contains antiproliferative, antiangiogenic, and apoptotic properties. Further evidence suggested that curcumin also suppresses tumor/colon cancer cell progression and angiogenesis by stimulating apoptosis and regulating immune response. Increased expression of the scavenging receptor Sortilin (SORT1), has been clinically observed in numerous invasive tumor biopsies. Procedures: In light of this, we developed a peptide conjugation platform and a new SORT1 receptor-mediated strategy to increase cell targeting selectivity and cell delivery of anticancer agents. As a proof-of-concept for phytochemicals, curcumin was conjugated to a SORT1-binding proprietary peptide (TH19P01). Curcumin-TH19P01 conjugate (TH1901) and unconjugated curcumin were tested on the proliferation of various cancer cells. Results: TH1901 showed a stronger anti-proliferation activity against cancer cells, with IC50 values up to 100-fold greater when compared to unconjugated curcumin. In addition, higher accumulation of fluorescence was detected for TH1901 indicating a more efficient cell internalization and release of curcumin from the conjugate. TH1901 uptake was reduced in the presence of SORT1 ligands neurotensin and progranulin as well as of free peptide confirming a preferential SORT1-mediated uptake of TH1901 in ES-2 ovarian cancer cells. Fluorescence microscopy showed that, in contrast to unconjugated curcumin, TH1901 induced cell apoptosis, and showed a stronger effect than unconjugated curcumin on TNF-alpha-induced intracellular signaling pathways involved in pro-inflammation processes. Interestingly, conjugation of curcumin also increased its in vitro stability in solution. In vivo, intraperitoneal administration of TH1901 (60 mg/kg/twice a week) inhibited growth of SORT1+ HT-29 colorectal cancer cell subcutaneous xenograft tumors, whereas at an equivalent dose unconjugated curcumin (15 mg/kg/twice a week) had no effect. Conclusion: Overall, these proof-of-concept experiments support the future development of this flexible and innovative platform to generate novel anticancer treatments. Citation Format: Borhane Annabi, Michel Demeule, Jean-Christophe Currie, Alain Larocque, Alain Zgheib, Christian Marsolais, Richard Béliveau. TH1901, a novel curcumin-peptide conjugate for the treatment of Sortilin-positive (SORT1+) cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6362.

Hydroxychloroquine and curcumin conjugates as multifunctional co drugs for the potential treatment of COVID-19: An in-silico based study

The present study has been undertaken to search the novel co drugs for fighting against the COVID-19 disease through an in- silico approach. We have designed eight co drugs by merging two drugs namely hydroxychloroquine, used in the treatment of COVID-19 and curcumin an immuno modulator. The two drugs were linked through a bio-cleavable hydrolyzable linker by three-step process. The designed co drugs were subjected for molecular docking studies to know their therapeutic efficacy against the COVID-19 main protease (Mpro) and Interleukin-1β. The designed co drugs have a promising binding affinity towards Mpro in the narrow range of binding energies between -28.2498 to -35.8648 kcal/mol when compared to the standard Remdesivir which has -21.8600 kcal/mol. Similarly the binding energies of designed co drugs against Interleukin -1β range between -25.8032 to -34.6973 kcal/mol when compared to the standard curcumin which has -17.3274 kcal/mol. Our findings demonstrated that the designed co drugs may be useful for the treatment of viral respiratory infection due to their additive therapeutic actions on the viral protein and modulating the immune response synergistically.

Curcumin Conjugates of Non-steroidal Anti-Inflammatory Drugs: Synthesis, Structures, Anti-proliferative Assays, Computational Docking, and Inflammatory Response.

In an effort to combine the anti‐proliferative effect of CUR‐BF2 and CUR compounds with anti‐inflammatory benefits of non‐steroidal anti‐inflammatory drugs (NSAIDs), a library of the bis‐ and mono‐NSAID/CUR‐BF2 and NSAID/CUR conjugates were synthesized by coupling flufenamic acid, flurbiprofen, naproxen, indomethacin, and ibuprofen to diversely substituted hydroxy‐benzaldehydes via an ester linkage, and by subsequent reaction with acetylacetone‐BF2 to form the bis‐ and the mono‐NSAID/CUR‐BF2 adducts. Since conversion to NSAID/CUR by the previously developed decomplexation protocol showed limited success, a set of NSAID/CUR conjugates were independently prepared by directly coupling the NSAIDs with parent curcumin. The bis‐NSAID/CUR‐BF2 and bis‐NSAID‐CUR hybrids exhibited low cytotoxicity in NCI‐60 assay, and in independent cell viability assay on colorectal cancer (CRC) cells (HCT116, HT29, DLD‐1, RKO, SW837, CaCo2) and in normal CR cells (CCD841CoN). By contrast, the mono‐naproxin and mono‐flurbiprofen CUR‐BF2 adducts exhibited remarkable anti‐proliferative and apoptopic activity in NCI‐60 assay most notably against HCT‐116 (colon), OVCAR‐3 (ovarian), and ACHN (renal) cells. Computational molecular docking calculations showed favorable binding energies to HER2, VEGFR2, BRAF, and Bcl‐2 as well as to COX‐1 and COX‐2, which in several cases exceeded known inhibitors. The main interactions between the ligands and the proteins were hydrophobic, although several hydrogen bonds were also observed. A sub‐set of six compounds that had exhibited little or no cytotoxicity were tested for their anti‐inflammatory response with THP‐1 human macrophages in comparison to parent NSAIDs or parent curcumin.

Curcumin Conjugates as Potential Therapeutics for Breast Cancer

This item presents the abstract for an oral presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.

Magnetotactic curcumin iButtonbots as efficient bactericidal agents

The microbial contamination of drinking water is one of the most major concerns of community health in the developing world. Numerous water-borne pathogens are rapidly evolving and becoming resistant to traditional antibiotics. To get an efficacious bactericidal response, an assembly of several antibiotics or increased dosage are being administered, which may produce adverse side effects after prolonged use. Here, we describe a proficient method for disinfecting water-borne coliform bacterial strains of Escherichia coli DH5 $$\upalpha $$ from contaminated water samples using magnetic microbots decorated with curcumin (CU) conjugates. These magnetic microbots, namely, iButtonbots were composed of soft Agaricus bisporus (button mushroom) microcapsules with inherit antimicrobial properties. The locomotives were coated with magnetite nanoparticles for their remote guidance towards cells and collection along with CU for more enhanced bactericidal response. CU, a major active constituent of the Indian dietary spice turmeric and edible button mushrooms are known to exhibit antimicrobial activity against a wide range of bacterial species. The synergic antibacterial effect of CU and mushroom constituents, imparts a profound bactericidal property to these magnetic microbots. We have demonstrated that microbots are capable of efficiently killing majority of bacterial cells in contaminated water samples. After extermination of bacteria, magnetic properties of embedded magnetite nanoparticles in porous mushroom matrix, allows collection of microbots from water samples. The presented biocompatible microbots offer an innovative method for rapid decontamination of bacteria-laden drinking water samples.

Green synthesis, characterization and biological evaluation of chitin glucan based zinc oxide nanoparticles and its curcumin conjugation

A well-organized, simplistic, and green route of chitin-glucan based zinc oxide nanoparticles (ChGC@ZnONPs) was synthesized using reducing and capping agent both in one as chitin-glucan complex (ChGC). Herein we report the bio-synthesis of Cur-ChGC@ZnONPs by the conjugation of curcumin (Cur) with ChGC@ZnONPs for the improvement of antioxidant and antibacterial activity. The synthesized nanoparticles were characterized by the UV–Visible (UV–Vis), particle size analyser, scanning electron microscope (SEM) with Energy-dispersive X-ray spectroscopy (EDX), Transmission electron microscope (TEM), X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR). Structure analysis, shape and crystalline size of nanomaterials were confirmed by scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM). The particle size analyser showed the particle size of nanomaterials and stability. Crystalline nature of both ChGC@ZnONPs and Cur-ChGC@ZnONPs were confirmed by the XRD spectra and FT-IR spectrum was used to examine the functional groups of nanomaterials. The antioxidant potential of conjugated nanomaterials were estimated using a DPPH free radical scavenging assay and ABTS+⁎ assay. This analysis showed that after loading of Cur, antioxidant activity increases. The antibacterial assessment of conjugated nanomaterials were tested by different microorganisms and showed excellent antibacterial activity.

Orientation-Inspired Perspective on Molecular Inhibitor of Tau Aggregation by Curcumin Conjugated with Ruthenium(II) Complex Scaffold.

Curcumin, a molecule of labile natural product, has multiplex pharmacological effects, including antioxidant, antimicrobial, and anticancer effects as well as anti-Alzheimer's disease (AD) properties. However, the drawbacks of curcumin such as poor stability and bioavailability seriously limited its application in drug development. Numerous literature studies suggested the conversion of curcumin to metal complexes and explored the clearance of β-amyloid fibrils by curcumin conjugates. However, the research about the inhibition effect of curcumin complex on τ protein aggregation is progressing slowly, and its interactive orientation with the related proteins from the steric effect has been ignored. Inspired by the perspective on interactive orientation, we conjugated curcumin molecule on the positive-charged scaffold of Ru(II) complexes (bipyridine for Ru1, phenanthroline for Ru2) to construct an octahedral structure. After being conjugated with a ruthenium octahedral framework, curcumin exhibited a stronger ability to not only inhibit aggregation of R3, the τ peptide corresponding to the third repeat unit of the microtubule binding domain (residues 306-336 in full τ) (Ru1 with an IC50 of 0.5 μM and Ru2 with an IC50 of less than 3 μM) but also disaggregate R3 fibers with dose-dependence through an exothermic and dynamic process. Autodock simulation was applied to get a hairpin-docking mode in the inhibition of R3 aggregation. Herein, our results provide a rational strategy emphasizing the interactive orientation from an octahedral steric structure to design the anti-AD drugs with natural compound.

A pH-sensitive delivery system based on N-succinyl chitosan-ZnO nanoparticles for improving antibacterial and anticancer activities of curcumin

Inherent selective cytotoxicity, antibacterial activity and unique physicochemical properties of ZnO nanostructures and chitosan (CS) make them promising candidates for drug delivery. In this study, ZnO nanoparticles functionalized by N-succinyl chitosan as a pH-sensitive delivery system were synthesized to enhance the therapeutic potential of curcumin (CUR). CS coated-ZnO nanoparticles were synthesized by a co-precipitation method in the presence of CS. Chemical modification of CS-ZnO particles was performed by succinic anhydride for introducing –COOH functional groups which were then activated using 1,1′‑carbonyldiimidazole for CUR conjugation. The spherical-like CUR-conjugated system (CUR-CS-ZnO) with the average particle size of 40 nm presented significantly enhanced water dispersibility versus free CUR. The experimental study of CUR release from the system showed a pH-sensitive release profile, which enabled drug delivery to tumors and infection sites. MTT and Annexin-V FITC/PI assays revealed the superior anticancer activity of CUR-CS-ZnO compared to free CUR against breast cancer cells (MDA-MB-231) by inducing the apoptotic response with no cytotoxic effects on HEK293 normal cells. Moreover, CUR conjugation to the system notably dropped the MIC (25 to 50-fold) and MBC values (10 to 40-fold) against S. aureus and E. coli. The features qualify the formulation for anticancer and antimicrobial applications in the future.

Zwitterionic Polymer Micelles with Dual Conjugation of Doxorubicin and Curcumin: Synergistically Enhanced Efficacy against Multidrug-Resistant Tumor Cells.

This paper reports a novel redox-sensitive micellar system for the co-delivery of doxorubicin (Dox) and a chemosensitizer (curcumin, Cur) to overcome the multidrug resistance (MDR) in cancer cells. Dox and Cur were co-conjugated onto a zwitterionic polymer, poly(carboxybetaine) (pCB), to form Cur-pCB-Dox that self-assembled into stable micelles (164.2 ± 4.8 nm). Single-drug conjugates (pCB-Dox and pCB-Cur) were prepared for comparisons. Compared to the high half-maximal inhibitory concentration (IC50) of Dox (437.2 μg/mL), the IC50 value of pCB-Dox (14.1 μg/mL) was only 1/33 that of Dox. Confocal laser scanning microscopy and flow cytometry revealed the greatly enhanced cell uptake of the conjugate due to the enhanced permeability and retention effect of tumor cells on the micellar conjugate. Co-delivery of pCB-Dox with pCB-Cur further reduced the IC50 value by 37% (8.9 μg/mL). More importantly, Cur-pCB-Dox exhibited the strongest cytotoxicity against MCF-7/Adr cells (IC50, 5.87 μg/mL) because the co-delivered Dox and Cur on one carrier specifically transported into the same cells, which inhibited the efflux of Dox by Cur, led to a higher intracellular Dox concentration and made the drugs exert synergistic effects at the targeting regions. The results proved the zwitterionic micelles as promising drug co-delivery vehicles for fighting against MDR.