Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated ...Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.展开更多
The goal of the research was to investigate the profile control and oil displacement characteristics of the polymer nanoparticles after high temperature swelling.The displacement parameters showed considerable influen...The goal of the research was to investigate the profile control and oil displacement characteristics of the polymer nanoparticles after high temperature swelling.The displacement parameters showed considerable influence on the plugging effect of the high-temperature swelled polymer nanoparticles,such as the core permeability,concentration of nanoparticles in the suspension,swelling time and swelling temperature,which makes it flexible to control the plugging effect by controlling displacement experiments conditions.Experimental results show that polymer nanoparticles dispersion system with a concentration of 500 mg/L is suitable for cores plugging with a permeability of 30×10^(-3)-150×10^(-3)μm^(2),even after aging at 150℃ for three months.The shunt flow experiments show that when the displacement factors are optimal values,the polymer nanoparticles after high temperature swelling to plug the high-permeability layer selectivity and almost do not clog the low-permeability layer.Oil recovery of homogeneous artificial core displacement experiment and a heterogeneous double-tube cores model are increased by 20%and 10.4%on the basis of water flooding.The polymer nanoparticles can be a great help for petroleum engineers to better apply this deep profile control and flooding technology.展开更多
Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid mo...Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid monomers.Five kinds of L-amino acids were acryloylated to obtain functional monomers:L-phenylalanine(Phe)and L-leucine(Leu)with hydrophobic side chains,L-glutamic acid(Glu)with negative charges,and L-lysine(Lys)and L-arginine(Arg)with positive charges.After incubating the NPs with fibrinogen,g-globulin,and human serum albumin(HSA)respectively,the NPs that incorporated Nacryloyl-Arg monomers(AArg@NPs)showed the strongest and most specific binding affinity to fibrinogen,when compared with g-globulin and HSA.Additionally,the fibrinogen-AArg binding model had the best docking scores,and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them.The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay,as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture.AArg@NPs had a strong selectivity for,and specificity to,fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.展开更多
The intramolecular cross-linking of single polymer chains can form single-chain nanoparticles(SCNPs),which have many applications.In this study,styrenic copolymers with pendent triphenylphosphine as the coordination s...The intramolecular cross-linking of single polymer chains can form single-chain nanoparticles(SCNPs),which have many applications.In this study,styrenic copolymers with pendent triphenylphosphine as the coordination site for platinum ions(Pt(Ⅱ))and benzocyclobutene as the latent reactive groups are synthesized.Triphenylphosphine groups in the chains can coordinate Pt(Ⅱ)and aid slight single-chain folding in dilute solution.The intramolecular cross-linking caused by the ring-open reaction of benzocyclobutene completes the single-chain collapse and forms stable SCNPs in dilute solution.Pt(Ⅱ)embedded in SCNPs can be further reduced to platinum atoms(Pt(0)).Pt(0)steadily and atomically dispersed in SCNPs exhibits better catalytic properties than normal polymer carried platinum particles do for the reduction of p-nitrophenol to p-aminophenol.展开更多
Photoacoustic imaging(PAI)is a hybrid imaging method based on photoacoustic(PA)effects,which is able to capture the structure,function,and molecular information of biological tissues with high resolution.To date,thera...Photoacoustic imaging(PAI)is a hybrid imaging method based on photoacoustic(PA)effects,which is able to capture the structure,function,and molecular information of biological tissues with high resolution.To date,therapeutic techniques under the guidance of PAI have provided new strategies for accurate diagnosis and precise treatment of tumors.In particular,conjugated polymer nanoparticles have been extensively inspected for PA-based cancer theranostics largely due to their superior optical properties such as tunable spectrum and large absorption coefficient and their good biocompatibility,and abundant functional groups.This mini-review mainly focuses on the recent advances toward the development of novel conjugated polymer nanoparticles for PA-based multimodal imaging and cancer photothermal therapy.展开更多
Immune checkpoint blockade(ICB)therapy is a widely favored anti-tumor treatment,but it shows limited response to non-immunogenic“cold”tumors and suffers from drug resistance.Photodynamic therapy(PDT),as a powerful l...Immune checkpoint blockade(ICB)therapy is a widely favored anti-tumor treatment,but it shows limited response to non-immunogenic“cold”tumors and suffers from drug resistance.Photodynamic therapy(PDT),as a powerful localized treatment approach,can convert a“cold tumor”into a“hot tumor”by inducing immunogenic cell death(ICD)in tumor cells,thereby enhancing tumor immunogenicity and promoting tumor immunotherapy.However,the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues.To address these issues,we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects,efficient immune checkpoint gene silencing,and a facile manufacturing process.The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA.PPNP is an amphipathic polymer that includes the near infrared-II(NIR-II)photosensitizer Aza-boron-dipyrromethene(Aza-BODIPY),a glutathione(GSH)-cleavable linker,and a cationic monomer derived from cholesterol.PPNP can self-assemble and efficiently load siRNA.Under laser irradiation,PPNP triggers a potent ICD cascade,causing the on-demand release of siPD-L1,reshaping the tumor’s immunosuppressive microenvironment,effectively inhibiting the growth of various tumors,and stimulating the immune memory.This study represents a generalized platform for PDT and gene silencing,designed to modulate immune-related signaling pathways for improved anticancer therapy.展开更多
Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of ...Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.展开更多
Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application p...Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application potential in information encryption,anti-counterfeiting,but remained challenging in improving the security.Herein,we described a self-erased time-resolved information encryption via using photoswitchable dual-color fluorescent polymeric nanoparticles(PDFPNs)containing two fluorescence dyes(blue and red)and photochromic spiroxazine derivatives.In view of the different thermo-induced isomerization rates of photochromic spiroxazine derivatives in different flexible substrates,the decoloration rate of PDFPNs can be programmatically tuned by regulating ratio between rigid polymer and flexible polymer.Therefore,after ultraviolet light(UV)irradiation,correct information could only be recognized in preestablished time during the self-erased process.Our results indicated that PDFPNs exhibited fast photo-responsibility(2 min),high fluorescence contrast,well-pleasing photo-reversibility(>20 times),and programmable thermo-responsiveness(24 s-6 h).We thus demonstrated their application in the selferased time-resolved information encryption and anti-counterfeiting with high security.展开更多
We have developed aggregation-induced emission （AIE） dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration （FDA） approved surfac...We have developed aggregation-induced emission （AIE） dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration （FDA） approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction （PCR） indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.展开更多
Chemically fueled dissipative self-assembly paves the way for innovative materials with lifelike properties and functions.Achievement of nonequilibrium systems with biocompatibility and biofunctions remains an importa...Chemically fueled dissipative self-assembly paves the way for innovative materials with lifelike properties and functions.Achievement of nonequilibrium systems with biocompatibility and biofunctions remains an important and challenging task.Here,we present biocompatible chemically fueled transient polymer nanoparticles and their applications in temporally programmable in vivo imaging.The lifetime of the transient polymer nanoparticles can be tuned by varying the concentration of polymer,adenosine triphosphate,and phosphatase.Moreover,the transient assembly of polymer nanoparticles can be paused for storage and then subsequently restored.The transient polymer nanoparticles exhibit good biocompatibility.Notably,we implement in vivo imaging in a temporally programmable fashion by using an autonomous fluorescence modulator of transient nanoparticles assembled from polymers with a fluorescence moiety.The results in this work provide a valuable way to achieve nonequilibrium self-assembly of synthetic systems with good biocompatibility and programmable biofunctions,accelerating innovative developments of nonequilibrium soft biomaterials.展开更多
Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of S...Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.展开更多
Polymer nanoparticles with dendrimer-Ag shell were prepared and their application in catalytic reduction of 4-nitrophenol （4-NP） was investigated. Cross-linked polystyrene （PS） microspheres were prepared through d...Polymer nanoparticles with dendrimer-Ag shell were prepared and their application in catalytic reduction of 4-nitrophenol （4-NP） was investigated. Cross-linked polystyrene （PS） microspheres were prepared through dispersion copolymerization of styrene, acrylic acid and crosslinking monomer 1, 2- divinylbenzene. PS microspheres with average size of 450 nm and narrow size distribution were used as support for the immobilization of dendrimer-Ag shell, The polyamidoamine （PAMAM） dendrimer shell was successively grafted onto the surface ofPS microspheres through repetitive Michael addition reaction of methyl acrylate （MA） and amidation of the obtained esters with large excess of ethylenediamine （EDA）. Silver nanoparticles were formed directly inside the PAMAM shell through reduction with NaBH4. The resulting PS@PAMAM-Ag nanopartides were packed in a stainless steel column and used successfully for catalytic reduction of 4-NP. This technique for packing catalytic polymer particles in a column could imnrove the efficiency of using the metal catalyst and the tedious seuaration in catalytic reaction.展开更多
Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is...Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.展开更多
Herein,we report self-assembly of tadpole-like single chain polymeric nanoparticles(TPPs)and the ultrasonic response of the resultant superparticles.The TPPs are with an intramolecularly crosslinked poly(2-(methacrylo...Herein,we report self-assembly of tadpole-like single chain polymeric nanoparticles(TPPs)and the ultrasonic response of the resultant superparticles.The TPPs are with an intramolecularly crosslinked poly(2-(methacryloyloxy)ethyl pent-4-ynoate)-rpoly(hydroxyethyl methacrylate)(PMAEP-r-PHEMA)chain as the"head"and a poly(2-(dimethylamino))ethyl methacrylate(PDMAEMA)linear chain as the"tail",and are pre-pared simply and emciently by Glaser-coupling of the pendant alkynes in the PMAEP-r-PHEMA block in the common solvent methanol.The formation of the TPPs was confirmed by gel permeation chromatograph,nuclear magnetic resonance spectroscopy,dynamic light scattering,static dynamic scattering,and transmission electron microscopy.In aqueous solution,the amphiphilic TPPs could self-assemble into regular superparticles,driven by aggregation of the hydrophobic"heads".Since in the structure there is no chain entanglement and the embedding of PDMAEMA chains disturb close-packing of the"heads",the superpartieles are responsive to a low-energy ultrasonic vibration,as evidenced by greatly enhanced release of the functional molecules from the superparticles by treatment of a low-energy ultrasound.Therefore,the superparticles should be very promising in the use as the drug carriers that can be manipulated from a long distance,considering that ultrasonic energy can be focused at a small area in a relatively long distance from the ultrasound-radiating source.展开更多
Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered dru...Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.展开更多
With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the ba...With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens.To address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared recently.The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms.The advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.展开更多
Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA...Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.展开更多
Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This s...Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.展开更多
Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polyme...Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.展开更多
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...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.61727823,51873160)the joint research project of Health and Education Commission of Fujian Province(Grant No.2019-WJ-20).
文摘Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.
基金funded by National Natural Science Foundation of China No.51874316 and 51274211National Key Scientific and Technological Project(Grant No.2017ZX05009-004)。
文摘The goal of the research was to investigate the profile control and oil displacement characteristics of the polymer nanoparticles after high temperature swelling.The displacement parameters showed considerable influence on the plugging effect of the high-temperature swelled polymer nanoparticles,such as the core permeability,concentration of nanoparticles in the suspension,swelling time and swelling temperature,which makes it flexible to control the plugging effect by controlling displacement experiments conditions.Experimental results show that polymer nanoparticles dispersion system with a concentration of 500 mg/L is suitable for cores plugging with a permeability of 30×10^(-3)-150×10^(-3)μm^(2),even after aging at 150℃ for three months.The shunt flow experiments show that when the displacement factors are optimal values,the polymer nanoparticles after high temperature swelling to plug the high-permeability layer selectivity and almost do not clog the low-permeability layer.Oil recovery of homogeneous artificial core displacement experiment and a heterogeneous double-tube cores model are increased by 20%and 10.4%on the basis of water flooding.The polymer nanoparticles can be a great help for petroleum engineers to better apply this deep profile control and flooding technology.
基金This work was supported by the Natural Science Foundation of Guangdong Province,China(Grant No.:2017A030313775)the Science and Technology Planning Project of Guangdong Province,China(Grant No.:2016A010103016)the Science and Technology Planning Project of Guangzhou City of Guangdong Province,China(Grant No.:201607010148).
文摘Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid monomers.Five kinds of L-amino acids were acryloylated to obtain functional monomers:L-phenylalanine(Phe)and L-leucine(Leu)with hydrophobic side chains,L-glutamic acid(Glu)with negative charges,and L-lysine(Lys)and L-arginine(Arg)with positive charges.After incubating the NPs with fibrinogen,g-globulin,and human serum albumin(HSA)respectively,the NPs that incorporated Nacryloyl-Arg monomers(AArg@NPs)showed the strongest and most specific binding affinity to fibrinogen,when compared with g-globulin and HSA.Additionally,the fibrinogen-AArg binding model had the best docking scores,and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them.The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay,as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture.AArg@NPs had a strong selectivity for,and specificity to,fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.
基金supported by the Fun dame ntal Research Funds for the Central Universities(China)(No.0500219216)the National Natural Science Foundation of China(No.21144006).
文摘The intramolecular cross-linking of single polymer chains can form single-chain nanoparticles(SCNPs),which have many applications.In this study,styrenic copolymers with pendent triphenylphosphine as the coordination site for platinum ions(Pt(Ⅱ))and benzocyclobutene as the latent reactive groups are synthesized.Triphenylphosphine groups in the chains can coordinate Pt(Ⅱ)and aid slight single-chain folding in dilute solution.The intramolecular cross-linking caused by the ring-open reaction of benzocyclobutene completes the single-chain collapse and forms stable SCNPs in dilute solution.Pt(Ⅱ)embedded in SCNPs can be further reduced to platinum atoms(Pt(0)).Pt(0)steadily and atomically dispersed in SCNPs exhibits better catalytic properties than normal polymer carried platinum particles do for the reduction of p-nitrophenol to p-aminophenol.
基金We acknowledge financial support from grants MYRG2014-00093-FHS,MYRG 2015-00036-FHS,MYRG2016-00110-FHS and MYRG2018-00081-FHS from the University of Macao in Macao and grants FDCT 0011/2018/A1 and FDCT 025/2015/A1 from the Macao government.
文摘Photoacoustic imaging(PAI)is a hybrid imaging method based on photoacoustic(PA)effects,which is able to capture the structure,function,and molecular information of biological tissues with high resolution.To date,therapeutic techniques under the guidance of PAI have provided new strategies for accurate diagnosis and precise treatment of tumors.In particular,conjugated polymer nanoparticles have been extensively inspected for PA-based cancer theranostics largely due to their superior optical properties such as tunable spectrum and large absorption coefficient and their good biocompatibility,and abundant functional groups.This mini-review mainly focuses on the recent advances toward the development of novel conjugated polymer nanoparticles for PA-based multimodal imaging and cancer photothermal therapy.
基金support from the National Natural Science Foundation of China(U23A20489,32171394)the National Key Research&Development Program of China(2021YFE0106900,2021YFC2302400)+1 种基金the Fundamental Research Funds for the Central Universities of China(2022CX01013)the Beijing Nova Program(Interdisciplinary Cooperation Project)from the Beijing Municipal Science&Technology Commission(20220484207).
文摘Immune checkpoint blockade(ICB)therapy is a widely favored anti-tumor treatment,but it shows limited response to non-immunogenic“cold”tumors and suffers from drug resistance.Photodynamic therapy(PDT),as a powerful localized treatment approach,can convert a“cold tumor”into a“hot tumor”by inducing immunogenic cell death(ICD)in tumor cells,thereby enhancing tumor immunogenicity and promoting tumor immunotherapy.However,the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues.To address these issues,we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects,efficient immune checkpoint gene silencing,and a facile manufacturing process.The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA.PPNP is an amphipathic polymer that includes the near infrared-II(NIR-II)photosensitizer Aza-boron-dipyrromethene(Aza-BODIPY),a glutathione(GSH)-cleavable linker,and a cationic monomer derived from cholesterol.PPNP can self-assemble and efficiently load siRNA.Under laser irradiation,PPNP triggers a potent ICD cascade,causing the on-demand release of siPD-L1,reshaping the tumor’s immunosuppressive microenvironment,effectively inhibiting the growth of various tumors,and stimulating the immune memory.This study represents a generalized platform for PDT and gene silencing,designed to modulate immune-related signaling pathways for improved anticancer therapy.
基金supported by National Natural Science Foundation of China(Nos.52173150 and U22A20315)the Guangzhou Science and Technology Program City-University Joint Funding Project(No.2024A03J0604)+2 种基金the Science and Technology Program of Guangzhou(No.2024A03J0431)the start-up funding for the Seventh Affiliated Hospital of Sun Yat-sen University(Shenzhen)(No.ZSQYRSFPD0053)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515111126)。
文摘Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.
基金financially supported by the National Key R&D Program of China(Nos.2023YFB3812400,2023YFB3812403)National Natural Foundation of China(Nos.52273206,52350233)+1 种基金Hunan Provincial Natural Science Foundation(No.2021JJ10029)Huxiang High-level Talent Gathering Project(No.2022RC4039).
文摘Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application potential in information encryption,anti-counterfeiting,but remained challenging in improving the security.Herein,we described a self-erased time-resolved information encryption via using photoswitchable dual-color fluorescent polymeric nanoparticles(PDFPNs)containing two fluorescence dyes(blue and red)and photochromic spiroxazine derivatives.In view of the different thermo-induced isomerization rates of photochromic spiroxazine derivatives in different flexible substrates,the decoloration rate of PDFPNs can be programmatically tuned by regulating ratio between rigid polymer and flexible polymer.Therefore,after ultraviolet light(UV)irradiation,correct information could only be recognized in preestablished time during the self-erased process.Our results indicated that PDFPNs exhibited fast photo-responsibility(2 min),high fluorescence contrast,well-pleasing photo-reversibility(>20 times),and programmable thermo-responsiveness(24 s-6 h).We thus demonstrated their application in the selferased time-resolved information encryption and anti-counterfeiting with high security.
基金This work was supported by the National Natural Science Foundation of China （NSFC） （61107017, 81301318）, the Start-up grant （M4080141.040） from Nanyang Technological University, Tier 1 Academic Research Funds （M4010360.040 RG29/10） from Singapore Ministry of Education and partially from the Singapore Ministry of Education under a Tier 2 Research Grant MOE2010-T2-2-010 （4020020.040 ARC2/11） and the grant from the Shenzhen Basic Research Project （JC201005280391A）
文摘We have developed aggregation-induced emission （AIE） dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration （FDA） approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction （PCR） indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.
基金This work was financially supported by the National Natural Science Foundation of China(NSFC)under grant no.21972054.
文摘Chemically fueled dissipative self-assembly paves the way for innovative materials with lifelike properties and functions.Achievement of nonequilibrium systems with biocompatibility and biofunctions remains an important and challenging task.Here,we present biocompatible chemically fueled transient polymer nanoparticles and their applications in temporally programmable in vivo imaging.The lifetime of the transient polymer nanoparticles can be tuned by varying the concentration of polymer,adenosine triphosphate,and phosphatase.Moreover,the transient assembly of polymer nanoparticles can be paused for storage and then subsequently restored.The transient polymer nanoparticles exhibit good biocompatibility.Notably,we implement in vivo imaging in a temporally programmable fashion by using an autonomous fluorescence modulator of transient nanoparticles assembled from polymers with a fluorescence moiety.The results in this work provide a valuable way to achieve nonequilibrium self-assembly of synthetic systems with good biocompatibility and programmable biofunctions,accelerating innovative developments of nonequilibrium soft biomaterials.
基金the National Natural Science Foundation of China(Nos.22174070 and 22205115)Natural Science Foundation of Jiangsu Province(No.BK20230060)+4 种基金Natural Science Foundation of Jiangsu University(No.21KJB150022)the Research startup fund of NJUPT(No.NY220149)Natural Science Foundation of NJUPT(No.NY221088)the Project of State Key Laboratory of Organic Electronics and Information Displays,Nanjing University of Posts and Telecommunications(Nos.GZR2022010012 and GZR2023010022)the Synergetic Innovation Center for Organic Electronics and Information Displays for the financial support.
文摘Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.
基金the Major Project (XK100100433,XK100100540)for Polymer Chemistry and Physics Subject Construction from Beijing Municipal Education Commission(BMEC),for financial support to this work
文摘Polymer nanoparticles with dendrimer-Ag shell were prepared and their application in catalytic reduction of 4-nitrophenol （4-NP） was investigated. Cross-linked polystyrene （PS） microspheres were prepared through dispersion copolymerization of styrene, acrylic acid and crosslinking monomer 1, 2- divinylbenzene. PS microspheres with average size of 450 nm and narrow size distribution were used as support for the immobilization of dendrimer-Ag shell, The polyamidoamine （PAMAM） dendrimer shell was successively grafted onto the surface ofPS microspheres through repetitive Michael addition reaction of methyl acrylate （MA） and amidation of the obtained esters with large excess of ethylenediamine （EDA）. Silver nanoparticles were formed directly inside the PAMAM shell through reduction with NaBH4. The resulting PS@PAMAM-Ag nanopartides were packed in a stainless steel column and used successfully for catalytic reduction of 4-NP. This technique for packing catalytic polymer particles in a column could imnrove the efficiency of using the metal catalyst and the tedious seuaration in catalytic reaction.
基金supported by the National Natural Science Foundation of China(Nos.82201135,22174070,and 61905122)Nanjing Clinical Research Center for Oral Diseases(No.2019060009)+2 种基金General project of Jiangsu Provincial Health Commission(No.M2021077)Scientific research fund of Jiangsu Medical Association(No.SYH-3201150-0007(2021002))the Natural Science Foundation of Jiangsu Province(No.BK20190735).
文摘Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.
基金This work was supported by the National Natural Science Foundation of China(No.21334001 and No.91127030).
文摘Herein,we report self-assembly of tadpole-like single chain polymeric nanoparticles(TPPs)and the ultrasonic response of the resultant superparticles.The TPPs are with an intramolecularly crosslinked poly(2-(methacryloyloxy)ethyl pent-4-ynoate)-rpoly(hydroxyethyl methacrylate)(PMAEP-r-PHEMA)chain as the"head"and a poly(2-(dimethylamino))ethyl methacrylate(PDMAEMA)linear chain as the"tail",and are pre-pared simply and emciently by Glaser-coupling of the pendant alkynes in the PMAEP-r-PHEMA block in the common solvent methanol.The formation of the TPPs was confirmed by gel permeation chromatograph,nuclear magnetic resonance spectroscopy,dynamic light scattering,static dynamic scattering,and transmission electron microscopy.In aqueous solution,the amphiphilic TPPs could self-assemble into regular superparticles,driven by aggregation of the hydrophobic"heads".Since in the structure there is no chain entanglement and the embedding of PDMAEMA chains disturb close-packing of the"heads",the superpartieles are responsive to a low-energy ultrasonic vibration,as evidenced by greatly enhanced release of the functional molecules from the superparticles by treatment of a low-energy ultrasound.Therefore,the superparticles should be very promising in the use as the drug carriers that can be manipulated from a long distance,considering that ultrasonic energy can be focused at a small area in a relatively long distance from the ultrasound-radiating source.
基金supported by National Key Clinical Specialties Construction Programthe National Natural Science Foundation of China(No.81602699)the Sichuan Science and Technology program(No.2019YFG0266)。
文摘Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.
基金financially supported by the National Natural Science Foundation of China(Nos.21620102005,51933006,and 52003184)。
文摘With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens.To address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared recently.The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms.The advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.
基金National Natural Science Foundation of China(Grant No.21877061)Natural Science Foundation of Jiangsu Province(Grant No.BK20171448)National and Local Joint Engineering Research Center of Biomedical Functional Materials。
文摘Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
基金the financial support received form National Natural Science Foundation of China(No.82073784)Jilin Province Science and Technology Development Program(No.20200801012GH)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province(No.2019C050-4).
文摘Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.
基金financially supported by the Ministry of Science and Technology of China(No.2022YFE0110200)the Natural Science Foundation of Hunan Province of China(No.2021JJ30680)the National Natural Science Foundation of China(Nos.52203198,52025035 and 52103195)。
文摘Combretastatin A4 phosphate(CA4P)is a potent vascular disrupting agent with good water solubility.However,it is only effective at high doses,which decreases clinical applicability.Herein,we designed stable CA4P polymeric nanoparticles(CA4P NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93%.The nanoparticles released CA4P in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4P(24.6%).Furthermore,the carrier components of CA4P NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4P NPs are safe and have significant potential for clinical translation.
基金supported by the National Natural Science Foundation of China(21674081)Fundamental Research Funds for the Central Universities(22120180109)
文摘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.
