Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate reverse micelles

The liquid-liquid extraction method using reverse micelles can simultaneously extract lipid and protein of oilseeds,which have become increasingly popular in recent years.However,there are few studies on mass transfer processes and models,which are helpful to better control the extraction process of oils and proteins.In this paper,mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate(AOT)/isooctane reverse micelles was investigated.The effects of stirring speed(0,70,140,and 210 r/min),temperature of extraction(30,35,40,45,and 50℃),peanut flour particle size(0.355,0.450,0.600,and 0.900 mm)and solidliquid ratio(0.010,0.0125,0.015,0.0175,and 0.020 g/mL)on extraction rate were examined.The results showed that extraction rate increased with temperature rising,particle size reduction as well as solid-liquid ratio increase respectively,while little effect of stirring speed(P>0.05)was observed.The apparent activation energy of extraction process was calculated as 10.02 kJ/mol and Arrhenius constant(A)was 1.91 by Arrhenius equation.There was a linear relationship between reaction rate constant and the square of the inverse of initial particle radius(1/r_(0)^(2))(P<0.05).This phenomenon and this shrinking core model were anastomosed.In brief,the extraction process was controlled by the diffusion of protein from the virgin zone interface of particle through the reacted zone and it was in line with the first order reaction.Mass transfer kinetics of peanut protein extracted by reverse micelles was established and it was verified by experimental results.The results provide an important theoretical guidance for industrial production of peanut protein separation and purification.

Antibiotic-based small molecular micelles combined with photodynamic therapy for bacterial infections

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics.Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs,but the mass proportion of carriers generally exceeds 90%of the nano-drug,resulting in low drug loading and limited therapeutic output.Herein,we fabricated a nanocarrier using antibiotics as the building blocks,minimizing the use of carriermaterials,significantly increasing the drug loading content and treatment effect.Firstly,we conjugated betaine carboxylate with ciprofloxacin(CIP)through an ester bond to form the amphiphilic conjugate(CIP-CB),which self-assembled into micelles(CIP-CBMs)in aqueous solutions,with a CIP loading content as high as 65.4%and pH-induced surface charge reversal properties.Secondly,a model photosensitizer(5,10,15,20-tetraphenylporphyrin(TPP))was encapsulated in CIP-CBMs,generating infection-targeted photodynamic/antibiotic combined nanomedicines(denoted as TPP@CIP-CBMs).Upon accumulation at infection sites or in deep bacterial biofilms,the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP,leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

Construction of curcumin-loaded micelles and evaluation of the anti-tumor effect based on angiogenesis

Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-targeting peptide NGR.Methods:The targeted polymer poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PEG-PLGA)modified with Asn–Gly–Arg(NGR)peptide was prepared and characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectrometry.NGR-PEG-PLGA was used to construct curcumin(Cur)-loaded micelles by the solvent evaporation method.The physicochemical properties of the micelles were also investigated.Additionally,we evaluated the antitumor efficacy of the polymer micelles(PM)using in vitro cytology experiments and in vivo animal studies.Results:The particle size of Cur-NGR-PM was 139.70±2.51 nm,and the drug-loading capacity was 14.37±0.06%.In vitro cytological evaluation showed that NGR-modified micelles showed higher cellular uptake through receptor-mediated endocytosis pathways than did unmodified micelles,leading to the apoptosis of tumor cells.Then,in vivo antitumor experiments showed that the modified micelles significantly inhibited tumor growth and were safe.Conclusions:NGR-modified micelles significantly optimized the therapeutic efficacy of Cur.This strategy offers a viable avenue for cancer treatment.

Preparation of adhesive resveratrol micelles and determination of drug content

Objective:Resveratrol polymer micelles with tissue adhesion were prepared and the content of resveratrol in the micelles was determined by HPLC.Method:The micelle adhesion experiment was carried out by polylysine orifice plate experiment and small animal fluorescence imaging method,and the micelle prescription was optimized to obtain resveratrol micelles with good adhesion.The separation was performed on a Shiseido SPOLAR C18 column(150 mm×4.6 mm,5μm)with methanol-water(42:58)as the mobile phase.The flow rate was 1.0 mL·min^(-1),the detection wavelength was 305 nm,the column temperature was 35℃,and the injection volume was 10μL.Results:Resveratrol micelles prepared with F127 alone had the best adhesion.The peak area and concentration of resveratrol had a good linear relationship in the concentration range of 10~200μg/mL(r=0.9996).The specificity,precision,recovery and stability all met the methodological requirements.Conclusion:In this experiment,resveratrol micelles with tissue adhesion were successfully prepared,and a method for the determination of resveratrol content in micelles was established.The method is accurate,rapid and simple.

pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery

Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems.The copolymers with reversible protonationedeprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release.These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect,or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway.The pH-sensitive micelles have been proved the specific tumor cell targeting,enhanced cellular internalization,rapid drug release,and multidrug resistance reversal.The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting.The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance.The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy,and is a novel promising platform for tumor-targeting drug delivery.

Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis

To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase(LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles(LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly(2-(dimethylamino) ethyl methacrylate)(PCL-PDMAEMA), methoxy polyethylene glycol-block-polycaprolactone(mPEG-PCL)and RGDfk conjugated polycaprolactone-block-polyethylene glycol(PCL-PEG-RGDfk). PCLPDMAEMA was synthesized via ring open polymerization(ROP) and atom transfer radical polymerization(ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering(DLS) and transmission electron microscope(TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.

Preparation and evaluation of poly(L-histidine) based pH-sensitive micelles for intracellular delivery of doxorubicin against MCF-7/ADR cells

In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.

Supersaturation induced by Itraconazole/Soluplus micelles provided high GI absorption in vivo

To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole(ITZ)/Soluplus~? solid dispersion. Solid dispersions prepared by hot melt extrusion (HME) were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM). Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox~? in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus~? micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox~?, ITZ tablets exhibited a 2.50-fold increase in the AUC (0–96) of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OHITZ) in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus~? enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer(ABL), resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus~?, which can induce supersaturation by micelleformation, may be of great assistance to the successful development of poorly watersoluble drugs.

Rheological properties of wormlike micelles formed in the sodium oleate/trisodium phosphate aqueous solution

Aqueous solution of anionic surfactant,sodium oleate（NaOA）,was studied by means of steady-state shear rheology and dynamic oscillatory technique.The system of NaOA/Na3PO4 showed high viscosity,strong viscoelasticity and good ability of countering Ca^2＋,Mg^2＋.The Maxwell model and Cole-Cole plot were applied to study the dynamic viscoelasticity of wormlike micelles.The microstructures of the wormlike micelles were characterized by FF-TEM.

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

Improved Anti-tumor Efficiency against Prostate Cancer by Docetaxel-loaded PEG-PCL Micelles

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Different Aggregation Behaviors of Tetra-(4-hydroxyphenyl) Porphyrin (THPPH_2) in the Inner Core and on the Surface of CTAB Micelles

The UV-Vis spectra of THPPH2 in CTAB micelles at pH7.2 and pH11.0 were analyzed to study the effect of micellar environments on the aggregation behaviors of this porphyrin.

A Combinative Assembly Strategy Inspired Reversibly Borate-Bridged Polymeric Micelles for Lesion-Specific Rapid Release of Anti-Coccidial Drugs

Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylboronic acid(PBA)were synthesized,of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA.The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges.The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract.After reaching the lesions,the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release,while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside.The drugmicelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation.The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable,safe and flexible anti-infectious drug delivery systems.

Formation of Copolymer-Ag Nanoparticles Composite Micelles in Three-dimensional Co-flow Focusing Microfluidic Device

A novel method was presented to create composite micelles of amphiphilic copolymers and Ag nanoparticles(NPs) in a three-dimensional co-flow focusing microfluidic device(3D CFMD). Self-assembly of the copolymers was initiated by the fast mixing of water and a blend dispersion of hydrophobic Ag NPs and amphiphilic copolymers. At the same time, the hydrophobic Ag NPs enter the core of copolymer micelles, based on the hydrophobic interaction. The copolymer-Ag NPs composite micelles have a core-shell structure with copolymer shell and Ag NPs core. COMSOL Multiphysics is used to simulate the concentration distribution of copolymers and Ag NPs under different flow rates. Co-assembly microfluidic conditions are determined based on simulation results. Under suitable microfluidic conditions, both block copolymers and gradient copolymers can co-assemble with hydrophobic Ag NPs to form composite micelles, respectively. This microfluidic coassembly method will have a good prospect in the preparation of composite micelles of amphiphilic copolymers and metal nanoparticles.

Mechanisms of Cytochrome C Extraction by Reverse Micelles

The extraction of cytochrome C was carried out by means of phase transfer technique with three different reverse micellar systems, i.e. , a CTAB micellar solution in n butyl alcohol chloroform(volume ratio 4∶1), an AOT micellar solution in isooctane and a SDSS D 2EHPA micellar solution in isooctane. The extraction mechanisms were studied. The results show that the extraction mechanisms for the same proteins with different types of reverse micellar systems can be distinct. The extraction of cytochrome C with CTAB and SDSS D 2EHPA reverse micellar systems are carried out according to the mechanism of electrostatic interaction. However, in the extraction of cytochrome C with the AOT reverse micellar system, the electrostatic interaction between the protein and the surfactant is not important.

Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel:A dual approach for in situ treatment of tumors

The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles) are able to increase the solubility of DTX inwater, and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles) can accelerate the formation of a depot of this drug-loaded system at the siteof administration. Therefore, the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem, with higher tumor inhibition effects and are less toxic to normal tissues.

Optically active micelles from self-assembly of MPEG-b-PMALM copolymer in water

Reported here is fabrication of optically active micelles with broad range of morphologies in water, such as spheres, cylinders, and vesicles, from self-assembly of poly（ethylene glycol） monomethyl ether-b-poly- （methacryloyl-L-leucine methyl ester） （MPEG-b-PMALM） copolymer, which was prepared via atom transfer radical polymerization （ATRP） from vinyl monomer bearing chiral amino acid moieties, N-methacryloyl L-leucine methyl ester （MALM）, using bromine （Br） end-capped poly（ethylene golycol） monomethylether （MPEG-Br） as macroinitiator in the presence of CuBr/Me6TREN as catalytic system.

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

The enantiomers of chiral drugs often have different potencies, toxicities, and biochemical properties. Therefore, the FDA and other worldwide regulatory agencies require manufactures to test and prove the enantiomeric purity of chiral drugs. Amino acid based molecular micelles (AABMM) have been used in chiral CE separations since the 1990’s because of their low environmental impact and because their properties can easily be tuned by changing the amino acids in the chiral surfactant head groups. Using molecular dynamics simulations to investigate the structures and properties of AABMM is part of an ongoing study focusing on investigating and elucidating the factors responsible for chiral recognition with AABMM. The results will be useful for the proper design and selection of more efficient chiral selectors. The micelles investigated contained approximately twenty covalently linked surfactant monomers. Each monomer was in turn composed of an undecyl hydrocarbon chain bound to a dipeptide headgroup containing of all combinations of L-Alanine, L-Valine, and L-Leucine. These materials are of interest because they are effective chiral selectors in capillary electrophoresis separations. Molecular dynamics simulation analyses were used to investigate how the sizes and positions of the headgroup amino acid R-groups affected the solvent accessible surface areas of each AABMM chiral center. In addition, headgroup dihedral angle analyses were used to investigate how amino acid R-group size and position affected the overall headgroup conformations. Finally, distance measurements were used to study the structural and conformational flexibilities of each AABMM headgroup. All analyses were performed in the context of a broader study focused on developing structure-based predictive tools to identify the factors responsible for a) self-assembly, b) function, c) higher ordered structure and d) molecular recognition of these amino acid based molecular micelles.

Polyelectrolyte complex micelles by self-assembly of polypeptide-based triblock copolymer for doxorubicin delivery

Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.