Phloretin Inhibits Quorum Sensing and Biofilm Formation in Serratia marcescens.

This study investigated the antivirulence capacity and mechanism of apple-skin-derived phloretin against Serratia marcescens NJ01, a vegetable spoilage bacterium. At 0.5 to 2 mg/mL doses, phloretin considerably inhibited the secretion of acyl homoserine lactones (AHLs), indicating that phloretin disrupted quorum sensing (QS) in S. marcescens NJ01. The dysfunction of QS resulted in reduced biofilms and the decreased production of protease, prodigiosin, extracellular polysaccharides (EPSs), and swimming and swarming motilities. Dysfunctional QS also weakened the activity of antioxidant enzymes and improved oxidative injury. The improved oxidative injury changed the composition of the membrane, improved membrane permeability, and eventually increased the susceptibility of biofilm cells to amikacin, netilmicin, and imipenem. The disrupted QS and enhanced oxidative stress also caused disorders of amino acid metabolism, energy metabolism, and nucleic acid metabolism, and ultimately attenuated the ability of S. marcescens NJ01 to induce spoilage. Our results indicated that phloretin can act as a potent drug to defend against spoilage by S. marcescens.

Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcumin.

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of -33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.

L-Cysteine-Modified Transfersomes for Enhanced Epidermal Delivery of Podophyllotoxin.

The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention (p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.

Microemulsion-Based Keratin-Chitosan Gel for Improvement of Skin Permeation/Retention and Activity of Curcumin.

Curcumin (Cur) is a kind of polyphenol with a variety of topical pharmacological properties including antioxidant, analgesic and anti-inflammatory activities. However, its low water solubility and poor skin bioavailability limit its effectiveness. In the current study, we aimed to develop microemulsion-based keratin-chitosan gel for the improvement of the topical activity of Cur. The curcumin-loaded microemulsion (CME) was formulated and then loaded into the keratin-chitosan (KCS) gel to form the CME-KCS gel. The formulated CME-KCS gel was evaluated for its characterization, in vitro release, in vitro skin permeation and in vivo activity. The results showed that the developed CME-KCS gel had an orange-yellow and gel-like appearance. The particle size and zeta potential of the CME-KCS gel were 186.45 ± 0.75 nm and 9.42 ± 0.86 mV, respectively. The CME-KCS gel showed desirable viscoelasticity, spreadability, bioadhesion and controlled drug release, which was suitable for topical application. The in vitro skin permeation and retention study showed that the CME-KCS gel had better in vitro skin penetration than the Cur solution and achieved maximum skin drug retention (3.75 ± 0.24 µg/cm2). In vivo experimental results confirmed that the CME-KCS gel was more effective than curcumin-loaded microemulsion (Cur-ME) in analgesic and anti-inflammatory activities. In addition, the CME-KCS gel did not cause any erythema or edema based on a mice skin irritation test. These findings indicated that the developed CME-KCS gel could improve the skin penetration and retention of Cur and could become a promising formulation for topical delivery to treat local diseases.

Branched polyethylenimine-assisted boronic acid functionalized magnetic nanoparticles for highly efficient capture of lincomycin and clindamycin.

As lincosamide antibiotics, lincomycin and clindamycin are widely used in the drug manufacturing industry for the health of human beings and animals. Thus, the quantitative detection of them in real samples is of great significance. Due to the presence of complex interfering components in actual samples, the separation and enrichment of lincomycin and clindamycin prior to analysis are key. Therefore, it is necessary to develop a non-complex, cost-effective enrichment method for them. A five- or six-membered boronic cyclic ester is formed through boronate affinity materials binding a cis-diol-containing compound in aqueous media, which is a reversible reaction. However, low binding capacity and affinity, and high binding pH of boronate affinity materials are key concerns. In this study, polyethylenimine-assisted 3-fluoro-4-formylphenylboronic acid functionalized magnetic nanoparticles were developed to capture efficiently cis-diol-containing lincomycin and clindamycin under neutral conditions. Thereinto, polyethylenimine (PEI) was applied as a scaffold to amplify the number of boronic acid moieties. And 3-fluoro-4-formylphenylboronic acid was used as an affinity ligand due to its excellent water solubility and low pKa value toward lincomycin and clindamycin. The results indicated that the prepared branched boronic acid-functionalized MNPs provided high binding capacity and fast binding kinetics under neutral conditions. Furthermore, the obtained MNPs exhibited relatively high binding affinity (Kd ≈ 10-4 M) and low binding pH (pH ≥ 6.0).

Silk peptide-hyaluronic acid based nanogels for the enhancement of the topical administration of curcumin.

The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of -13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 µg/cm2). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs.

Hyaluronic Acid Micelles for Promoting the Skin Permeation and Deposition of Curcumin.

Background: The poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs. Methods: In this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed. Results: The mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and -26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin. Conclusion: CUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.

Pentapeptide modified ethosomes for enhanced skin retention and topical efficacy activity of indomethacin.

Challenges associated with topical analgesics and anti-inflammatory drugs include poor drug penetration and retention at the desired lesion site. Therefore, improving these challenges would help to reduce the toxic and side effects caused by drug absorption into the systemic circulation and improve the therapeutic efficacy of topical therapeutic drugs. Pentapeptide (KTTKS) is a signal peptide in skin tissue, it can be recognized and bound by signal recognition particles. In the current study, we successfully prepared novel indomethacin (IMC) loaded KTTKS-modified ethosomes (IMC-KTTKS-Es), and the physicochemical properties and topical efficacy were investigated. Results showed that the prepared IMC-KTTKS-Es displayed a particle size of about 244 nm, a negative charge, good deformability, and encapsulation efficiency (EE) exceeding 80% for IMC, with a sustained release pattern. In vitro percutaneous permeation studies revealed that the skin retention was increased after the drug was loaded in the IMC-KTTKS-Es. Confocal laser scanning microscopy also showed improved skin retention of IMC-KTTKS-Es. In addition, IMC-KTTKS-Es showed improved topical analgesic and anti-inflammatory activity with no potentially hazardous skin irritation. This study suggested that the IMC-KTTKS-Es might be an effective drug carrier for topical skin therapy with a good safety profile.

Hyaluronan-modified transfersomes based hydrogel for enhanced transdermal delivery of indomethacin.

Hyaluronic acid (HA), as a hygroscopic and biocompatible molecule, has displayed unique permeation enhancement in transdermal delivery systems. Hence, indomethacin (IND) was encapsulated in HA-modified transfersomes (IND-HTs) to enhance transdermal IND delivery to reduce adverse effects in this study. The physiochemical properties of IND-HTs were characterized. Results showed that the prepared IND-HTs were spherical and revealed good entrapment efficiency (87.88 ± 2.03%), with a nanometric particle size (221.8 ± 93.34 nm). Then, IND-HTs were further incorporated into a carbopol 940 hydrogel (IND-HTs/Gel) to prolong retention capacity on the skin. The in vitro release and skin permeation experiments of IND-HTs/Gel were carried out with the Franz diffusion cells. It was found that IND-HTs/Gel exhibited sustained drug release, as well as superior drug permeation and flux across the skin. Confocal laser scanning microscopy showed improved penetration of HTs/Gel with a wider distribution and higher fluorescence intensity. The hematoxylin-eosin stained showed that HA improved the transdermal effect by changing the microstructure of skin layers and decreasing skin barrier function. In addition, IND-HTs/Gel showed significant analgesic activity in hot plate test and no potentially hazardous skin irritation. This study indicated that the developed IND-HTs/Gel could be a promising alternative to conventional oral delivery of IND by topical administration.

Rapid determination of 2,4-diaminopyrimidine residues through sample pretreatment using immunomagnetic bead purification along with HPLC-UV.

To reduce matrix interference and realize simultaneous detection of multiple homologous compounds (trimethoprim (TMP), diaveridine (DVD), ormetoprim (OMP), baquiloprim (BQP), and aditoprim (ADP) in pig, cattle, chicken, and fish muscles), an immunomagnetic bead (IMB)-based sample purification pretreatment with HPLC-UV was developed. A broad-spectrum monoclonal antibody (mAb, named 14C6) was prepared and conjugated with carboxylic-acid-functionalized magnetic nanoparticles using the active ester method to obtain IMBs for sample purification. The extraction solvent was optimized based on the extraction efficiency. Good linearity was observed for all the five analytes (10-200 µg/kg) with the LOD and LOQ of 5 and 10 µg/kg, respectively. The mean recoveries ranged from 62.5% to 76.9%, while the coefficient of variation was <12.2%. The IMB method afforded greater sample purification and enrichment than those achieved with the SPE column-based conventional method. Hence, the IMB-based sample purification is a useful tool to determine 2,4-diaminopyrimidine residues in edible animal tissues.

Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention.

BACKGROUND: Challenges associated with local antibacterial and anti-inflammatory drugs include low penetration and retention of drugs at the expected action site. Additionally, improving these challenges allows for the prevention of side effects that are caused by drug absorption into the systemic circulation and helps to safely treat local skin diseases. METHODS: In the current study, we successfully prepared a thiolated pluronic F127 polymer micelles (BTFM), which binds to keratin through a disulphide bond, to produce skin retention. In addition, the small particle size of polymer micelles promotes the penetration of carriers into the skin. The current study was divided into two experiments: an in vitro experiment; an in vivo experiment that involved the penetration of the micelle-loaded drugs into the skin of rats, the skin irritation test and the anti-inflammatory activity of the drug-loaded micelles on dimethyl benzene-induced ear edema in mice. RESULTS: Results from our in vitro transdermal experiment revealed that the amount of drug absorbed through the skin was decreased after the drug was loaded in the BTFM. Further, results from the vivo study, which used fluorescence microscopy to identify the location of the BTFM after penetration, revealed that there was strong fluorescence in the epidermis layer, but there was no strong fluorescence in the deep skin layer. In addition, the BTFM had a very good safety profile with no potentially hazardous skin irritation and transdermal administration of BTFM could significantly suppress ear edema induced by dimethyl benzene. Therefore, these findings indicated that BTFM reduced the amount of drug that entered the systemic circulation. Our results also demonstrated that the BTFM had a certain affinity for keratin. CONCLUSION: Our experimental results suggest that the BTFM may be an effective drug carrier for local skin therapy with good safety profile.

Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives.

For the development of potential anti-prostate cancer agents, 24 kinds of novel naftopidil-based arylpiperazine derivatives have been synthesized and characterized by spectroscopic methods. Their antitumor activities were evaluated against several classical prostate cancer cell lines including PC-3, LNCaP, and DU145. Among all the compounds, 9, 13, 17, 21 and 27 showed strong cytotoxic activities against DU145 cells (IC50 < 1 µM). Further testing confirmed that compound 17 inhibited the growth of DU145 cells by inducing cell cycle arrest at G0/G1 phase. Besides, antagonistic activities of compounds (9, 13, 17, 21 and 27) towards a1-ARs (α1A, α1B, and α1D) were further evaluated using dual-luciferase reporter assays, and the compounds 13 and 17 exhibited better a1-ARs subtype selectivity. The structure-activity relationship (SAR) of these developed arylpiperazine derivatives was rationally discussed. Taken together, these results suggested that further development of such compounds may be of great interest.

Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating.

In this study, glucose transporter and folic acid (FA) receptor-mediated Pluronic P105 polymeric micelles loaded with DOX (GF-DOX) were prepared for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. The pH-triggered DOX release of GF-DOX indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The transport of GF-DOX across the in vitro BBB model showed that GF-DOX exhibited higher BBB transportation ability with the transporting ratio of 21.47% in 4 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model for the combined effect of the brain targeting by transportation of glucose transporter and active tumor cell targeting by FA receptor-mediated endocytosis. Moreover, minimized weight changes and high suppression ratio of tumor growth were observed after intravenous injection of GF-DOX. In conclusion, the glucose transporter and FA dual-targeting micelles would provide a safe and effective strategy for new modalities to treat brain tumor.

Octreotide-mediated tumor cell uptake and intracellular pH-responsive drug delivery of the self-assembly supramolecular nanocarrier.

In this study, DOX-loaded supramolecular nanocarrier (DLSC) was assembled by using two new amphiphilic polymers, octreotide-polyethylene glycol monostearate (OPMS) and N-octyl-N-succinyl O-carboxymethyl chitosan (OSCC). The characteristics of the DLSC were investigated. The results indicated that the significant pH-triggered release in vitro. The cellular uptake of DLSC was much higher than that of DOX-loaded OSCC micelles (DLOM) in the SMMC-7721 (somatostatin receptor (SSTR) over-expressed cell) cells, which suggested the SSTR-mediated properties. A considerable amount of drug entered the nucleus due to the pH-triggered deformation of the supramolecular structure and rapid release of drug in acidic endosomes of tumor cells. The killing efficacy was much higher than that of DLOM in the SMMC-7721. In S180 sarcoma-bearing KM mice, the biodistribution and therapeutic activity were studied. DLSC showed extended circulation time in plasma, decreasing drug concentrations in the heart and accumulating drug concentrations in the pancreas and tumor. In addition, minimized weight changes and cardiac toxicity, high suppression ratio of tumor growth and longer survival time were observed after intravenous injection of DLSC. The studies suggested that the supramolecular nanocarrier constructed of different designated polymers with multiple functions would be one of the most effective approaches for active targeting drug delivery.

Effect of octreotide surface density on receptor-mediated endocytosis in vitro and anticancer efficacy of modified nanocarrier in vivo after optimization.

The objective of the present work was to investigate the optimum density of octreotide on the surface of nanostructured lipid carriers (NLC) loaded with hydroxycamptothencine (HCPT) to enhance receptor-mediated endocytosis and tumor targeting selectivity. Different amounts of octreotide-polyethylene glycol (100) monostearate (OPMS), a ligand for somatostatin receptors (SSTRs), were coupled into NLC. In vitro evaluation of OPMS modified NLCs (O-NLCs) was done by studying the physicochemical properties, drug release, cellular uptake and cytotoxicity. Whereas in vivo evaluation was done by studying the tissue distribution in S180 tumor-bearing mice through ex vivo fluorescence imaging and HCPT quantitative study. The results showed that O-NLCs with an average size of ∼100 nm possessed obvious sustained release. When OPMS was used in the amount of 5 µmol (O5-NLC) highest cellular uptake, cytotoxicity in SMMC-7721 cell line and remarkable accumulation in S180 tumor were observed. The treatments of O5-NLC brought about significant tumor inhibition and prolonged the median survival time as compared with HCPT, unmodified NLC and the pegylated NLC (P5-NLC) groups. It appears that to achieve a more rational approach of receptor mediated tumor targeted drug delivery system the surface density of the targeting moiety on the surface of nanocarriers should be considered.

Octreotide-modified and pH-triggering polymeric micelles loaded with doxorubicin for tumor targeting delivery.

A multifunctional mixed micelle was assembled for drug targeting delivery by combining two newly synthesized amphiphilic polymers, which were octreotide-polyethylene glycol-monostearate (OPMS) and N-octyl-N-succinyl-O-carboxymethyl chitosan (OSCC), respectively. The mixed micelle was designed to be characterized with long circulation, somatostatin receptors (SSTR)-mediated endocytosis and pH sensitivity. A series of assembling proportions of OPMS and OSCC was tested to reveal the effect of compositions on the functions. The particle size, zeta potential, drug loading and critical micelle concentration were examined. The dialysis test indicated a pH-triggering release behavior of the doxorubicin-loaded mixed micelle (DLMM), and faster release in acidic media (pH 4.0-6.0) in response to the protonation of carboxyl group. In addition, the PEG segments could efficiently protect the mixed micelle from plasma protein adsorption in vitro, and the DLMM composed of 20% OPMS and 80% OSCC provided the longest residence time after intravenous injection in rats in vivo. Due to SSTR mediated endocytosis, the significantly higher uptake of DLMM was observed in the tumor cells (SMMC-7721), compared with that in the normal cells (CHO) without SSTR expression. All the results suggested that the mixed micelle with multifunctional characteristics could be used as an effective approach for tumor treatment.

Effect of octreotide-polyethylene glycol(100) monostearate modification on the pharmacokinetics and cellular uptake of nanostructured lipid carrier loaded with hydroxycamptothecine.

A new conjugate, octreotide-polyethylene glycol(100) monostearate (OPMS), was developed for the enhancement of targeting delivery of hydroxycamptothecine (HCPT) loaded in nanostructured lipid carrier (NLC). 2 × 10(-3) and 5 × 10(-3) mmol of OPMS were respectively used to modify NLC so that the targeted nanocarriers with low and high ligand density were obtained. For comparison, the pegylated NLCs without octreotide were prepared by adding equal molar amounts of polyethylene glycol(100) monostearate (PGMS). The relation between the modification levels and properties of various NLCs were studied in vivo and in vitro. At a high modification level, a slower release rate of HCPT and the more stable nanocarriers was achieved. At the same time, the fixed aqueous layer thickness (FALT) and average surface density of PEG chains (SD(PEG)) was increased, but the distance (D) between two neighboring PEG grafting sites became narrower. The in vivo pharmacokinetic study in healthy rat indicated that the modified NLCs had a longer circulation than NLC (P < 0.05) due to pegylation effect and OPMS modified NLCs had larger MRT and AUC(0-t) than that of PGMS modified NLCs at the same modification level. Furthermore, the florescence microscopy observation also showed the targeting effect of octreotide modification on somatostatin receptors (SSTRs) of tumor cell (SMMC-7721). The uptake of SMMC-7721 was much more than that of normal liver cell (L02) for OPMS modified NLC, and the highest uptake was observed for 5 × 10(-3) mmol of OPMS modified one. No obvious difference was found among the L02 uptake of OPMS modified NLCs and NLC, but their uptake was higher than that of PGMS modified NLCs. All the results indicated that the OPMS highly modified NLCs would improve the effect of antitumor therapy by inhibiting the degradation, evading RES and enhancing the drug uptake of tumor cells.

Preparation of a cationic nanoemulsome for intratumoral drug delivery and its enhancing effect on cellular uptake in vitro.

To develop an appropriate carrier for intratumoral drug delivery, cetyltrimethylammonium bromide (CTAB) modified nanoemulsome (CTAB-NES) was designed and prepared by solvent evaporation method. Coumarin-6 was chosen as the fluorescent probe and the conventional nanoemulsome (NES) without CTAB modification served as a control. The results demonstrated that CTAB-NES had a smaller particle size of 71.9 +/- 4.32 nm, considerate positive zeta potential of +48.7 +/- 0.2 mV, preferably entrapment efficiency of 97.483 +/- 0.693% and the release of coumarin-6 in 24 h was little. The in vitro cytotoxicity of CTAB-NES to the CHO cells and MCF-7 cells increased consistently with concentrations and was higher than that of NES, especially to the cancer cells. Both the fluorescence microscopy images and HPLC assay verified that the cellular uptake of CTAB-NES in MCF-7 cells was much higher than that of NES, and the uptake was time-, concentration- and temperature- dependent. The uptake mechanism results demonstrated that the internalization of CTAB-NES and NES involved clathrin- and caveolae-mediated endocytosis while macropinocytosis only influenced the uptake of CTAB-NES in MCF-7 cells for CTAB could mediate adsorptive pinocytosis. Thus, CTAB-NES with high positive charge and good intracellular uptake ability could be a promising drug carrier for intratumoral drug delivery.