LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL.To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles.The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination therapy.Hence,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

Polymer Vesicles with Upper Critical Solution Temperature for Near-infrared Light-triggered Transdermal Delivery of Metformin in Diabetic Rats

Near-infrared light(NIR)triggered transdermal drug delivery systems are of great interest due to their on-demand drug release,which enable to enhance drug treatment efficiency as well as reduce side effect.Herein,a NIR-triggered microneedle(MN)patch array has been fabricated through depositing the photothermal conversion agent and anti-diabetic drug-loaded polymer vesicles with upper critical solution temperature(UCST)into dissolvable polymer matrix.The UCST-type polymer has a clearing point temperature of 41℃ and the drug-loaded polymer vesicles present excellent NIR-triggered and temperature responsive drug release behavior in vitro due to the disassociation of polymer vesicles upon NIR irradiation.After applying MNs to diabetic rats,significant hypoglycemic effect is achieved upon interval NIR irradiation and the blood glucose concentration can decrease to normal state for several hours,which enables to achieve the goal of on-demand drug release.This work suggests that the NIR-triggered MN drug release device has a potential application in the treatment of diabetes,especially for those requiring an active drug release manner.

CO_2-sensitive Amphiphilic Triblock Copolymer Self-assembly Morphology Transition and Accelerating Drug Release from Polymeric Vesicle

A series of triblock copolymers, containing a CO_2-switchable block poly（2-（dimethylamino）ethyl methacrylate）（PDM） block and two symmetrical hydrophilic blocks polyacrylamide（PAM）, were synthesized using atom transfer radical polymerization（ATRP） method. The p H and conductivity tests showed that the triblock copolymer exhibited switchable responsiveness to CO_2, i.e. a relatively low conductivity of solution could be switched on and off by bubbling and removing of CO_2, and the triblock copolymer aqueous solution displayed a CO_2-switchable viscosity variation. The changes were all attributed to protonation of tertiary amine groups in PDM blocks and proven by 1 H-NMR. Cryogenic transmission electron microscopy and dynamic light scattering characterization demonstrated that the viscosity variation was the result of a unilamellar vesicle-network aggregate structure transition. The release of rhodamine B from the vesicles with and without CO_2 stimuli showed the potential application in drug delivery domains; after CO_2 bubbling, the drug release rate could be accelerated. Finally, reasonable mechanism of CO_2-switchable morphology changes and CO_2-induced drug release was proposed.

Polymersomes:From Macromolecular Self-Assembly to Particle Assembly

What is the most favorite and original chemistry developed in your research group?Ring-opening polymerization-induced self-assembly of N-carboxyanhydrides(NCA-PISA),and fusion-induced particle assembly(FIPA).How do you get into this specific field?Could you please share some experiences with our readers?NCA-PISA was developed to solve the biodegradability problem of nanoparticles by traditional PISA,while FIPA was inspired by nature.

Polymer nanodisks by collapse of nanocapsules

It is an important challenge to make disk-like polymeric nanostructures. Herein we report a facile method for preparing polymer nanodisks by self-collapse of nanocapsules self-assembled from a statistical copolymer after partial hydrolysis. We find that partial hydrolysis of the statistical copolymer is crucial for the formation of nanodisks as it affords a suitable rigidity for the membrane of nanocapsules. The nanodisk structure has been confirmed by transmission electron microscopy(TEM), scanning electron microscopy(SEM) and atomic force microscopy(AFM) studies with a thickness of 6.3±0.2 nm. Overall, our results demonstrated a new method for making disk-like nano-objects.

Green Stereoregular Polymerization of Poly(methyl methacrylate)s Through Vesicular Catalysis

Stereoselective polymerization can yield polymers with specific tacticity and properties,and it is an essential topic throughout polymer synthesis history.Herein,we report for the first time on a vesicular catalysis method to realize the green stereoregular polymerization of isotactic-rich poly(methyl methacrylate)(PMMA)in water and at ambient temperature and pressure,namely by conducting the polymerization of MMA monomers in the confined 5-10 nm thick hydrophobic layers of hyperbranched polymer vesicles.The isotactic degree of the as-prepared PMMAs increases from 12% to 40% with the decrease of vesicle size from 840 to 85 nm in hydrodynamic diameter(Dh)due to the conformation confinement effect of MMA monomers inside the thin vesicle membranes through a curvature-dependent way.The present work has extended the scope of green chemistry,and it also represents a new application of polymer vesicles in stereoregular polymerization.

On the origin and regulation of ultrasound responsiveness of block copolymer nanoparticles

Noninvasive ultrasound is more convenient and easily accessible for controlled drug delivery of polymeric nanoparticles than many other stimuli.However,controlled ultrasound responsiveness is rather challenging as the mechanism is still unclear.In this article,we disclose the origin and the key regulating factors of ultrasound responsiveness of block copolymer nanoparticles such as simple vesicles,framboidal vesicles,lamellae,beads-like micelles and complex micelles that are self-assembled from a range of poly(ethylene oxide)-b-polymethacrylates based model copolymers.We discover that the intrinsic ultrasound responsiveness of block copolymer nanoparticles thermodynamically originates from their metastable states,and its expression kinetically relates to the mobility of the hydrophobic segments of block copolymers.Specifically,the self-assembly temperature(Ts) that has been usually considered as a less important factor in most of macromolecular self-assembly systems,and the solvents for the selfassembly are two dominant regulating factors of the ultrasound responsiveness because they determine the thermodynamic state(metastable or stable) of nanoparticles.For example,simple vesicles with good or excellent ultrasound responsiveness can be prepared in THF/water when the Tsis around or slightly below the glass transition temperature(Tg) of the hydrophobic segment of the block copolymer because the combination of this solvent with this Tsfacilitates the formation of metastable vesicles.By contrast,thermodynamically stable solid nanoparticles such as spherical micelles and lamellae(mainly formed in DMF/water)are not sensitive to ultrasound at all,neither are the vesicles in THF/water at stable states when the Tsis highly above Tg.In addition,we unravel that the responsive rate is highly dependent on the sonication temperature(Tu),i.e.,the higher the Tu,the faster the rate.Overall,the above important findings provide us with a fresh insight into how to design ultrasound-responsive nanoparticles and may open new avenues for synthesizing translational noninvasively responsive drug carriers.