In the tracking problem for the maritime radiation source by a passive sensor,there are three main difficulties,i.e.,the poor observability of the radiation source,the detection uncertainty(false and missed detections...In the tracking problem for the maritime radiation source by a passive sensor,there are three main difficulties,i.e.,the poor observability of the radiation source,the detection uncertainty(false and missed detections)and the uncertainty of the target appearing/disappearing in the field of view.These difficulties can make the establishment or maintenance of the radiation source target track invalid.By incorporating the elevation information of the passive sensor into the automatic bearings-only tracking(BOT)and consolidating these uncertainties under the framework of random finite set(RFS),a novel approach for tracking maritime radiation source target with intermittent measurement was proposed.Under the RFS framework,the target state was represented as a set that can take on either an empty set or a singleton; meanwhile,the measurement uncertainty was modeled as a Bernoulli random finite set.Moreover,the elevation information of the sensor platform was introduced to ensure observability of passive measurements and obtain the unique target localization.Simulation experiments verify the validity of the proposed approach for tracking maritime radiation source and demonstrate the superiority of the proposed approach in comparison with the traditional integrated probabilistic data association(IPDA)method.The tracking performance under different conditions,particularly involving different existence probabilities and different appearance durations of the target,indicates that the method to solve our problem is robust and effective.展开更多
For the problem of deterministic parameter estimate, the theoretical lower bound of esti- mate error is the Cramér-Rao bound; while for random parameter, the lower bound of estimate error is generally termed by P...For the problem of deterministic parameter estimate, the theoretical lower bound of esti- mate error is the Cramér-Rao bound; while for random parameter, the lower bound of estimate error is generally termed by Posterior Cramér-Rao Bound (PCRB). Under the background of passive tracking where the target's state can be seen as a time-varying random parameter, PCRB of the state estimate error is analyzed in this paper, and the relation between PCRB and varied condition is also fully in- vestigated using different simulation examples. The presented analytical method provides a theoretical base for performance assessment of all kinds of suboptimal estimate algorithms used in practice.展开更多
A marginalized particle filtering (MPF) approach is proposed for target tracking under the background of passive measurement. Essentially, the MPF is a combination of particle filtering technique and Kalman filter. ...A marginalized particle filtering (MPF) approach is proposed for target tracking under the background of passive measurement. Essentially, the MPF is a combination of particle filtering technique and Kalman filter. By making full use of marginalization, the distributions of the tractable linear part of the total state variables are updated analytically using Kalman filter, and only the lower-dimensional nonlinear state variable needs to be dealt with using particle filter. Simulation studies are performed on an illustrative example, and the results show that the MPF method leads to a significant reduction of the tracking errors when compared with the direct particle implementation. Real data test results also validate the effectiveness of the presented method.展开更多
Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG:poly(ethylene glycol);LA:L-lactide;DHP:2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-micelles)...Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG:poly(ethylene glycol);LA:L-lactide;DHP:2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-micelles) was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P(LA-co-DHP) followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P(LA-co-DHP) was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc(ZnEt2) as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM(transmission electron microscope) or 80 nm by DLS(dynamic light scattering).Their in vitro cell uptake experiment by CLSM(confocal laser scanning microscopy) and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration(fluorescent intensity) in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.展开更多
Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcuta...Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcutaneous form.Treatment of VL includes chemotherapeutic agents which are associated with some major hurdles like toxicities,parenteral administration,high cost,parasite resistance and stability.Hence,there is an urgent requirement to develop novel chemotherapeutic agents or repurposing of existing drugs against VL.Developing formulation of new chemical entity for the treatment of VL is laborious,time consuming and associated with huge financial burden.However,screening of existing chemotherapeutic agents is a good alternative to avail cost-effective treatment option for VL.Non-PEGylated liposome encapsulated doxorubicin(Myocet®)is proposed as an alternative treatment option for VL in this review article.Here,we covered the fundamental aspects of VL,loophole associated with available current treatment strategies and non-PEGylated liposome encapsulated doxorubicin as a novel alternative formulation for treating VL,as this liposomal delivery system of doxorubicin might passively target the intra-cellular regions of macrophage.展开更多
In the state estimation of passive tracking systems, the traditional approximate expression for the Cramero-Rao lower bound (CRLB) does not take two factors into consideration, that is, measurement origin uncertaint...In the state estimation of passive tracking systems, the traditional approximate expression for the Cramero-Rao lower bound (CRLB) does not take two factors into consideration, that is, measurement origin uncertainty aad state noise. Such treatment is only valid in ideal situation but it is not feasible in actual situation. In this article, considering the two factors, the posterior Cramer-Rao lower bound (PCRLB) recursion expression for the error of bearing-only tracking is derived. Then, further analysis is carried out on the PCRLB. According to the final result, there are four main parameters that play a role in the performance of the PCRLB, that is, measurement noise, detection probability, state noise and clutter density, amongst which the first two have greater impact on the performance of the PCRLB than the others.展开更多
The study of wave guide invariant in underwater acoustics is one of attracted topics in recent 30 years. The interferences of direct wave and reflect wave from sea surface and sea bottom of underwater target radiated ...The study of wave guide invariant in underwater acoustics is one of attracted topics in recent 30 years. The interferences of direct wave and reflect wave from sea surface and sea bottom of underwater target radiated noise inherent the information of target distance. Extraction of these distance information will provide a possible new way in passive ranging for underwater target. The theoretical analysis and the results of at sea experiments show that the LOFAR (Low Frequency Analysis Record) figure inherently contains the range and moving information of passive acoustic sources, even in the situation that the receiver is only one single hydrophone. The theoretical analysis of extraction of target distance information by using wave guide invariant is presented in this paper. It is shown that, based on the interference striation pattern of target, the hydrophone array system is possible to extract the distance information with quite high array gain. Although the mathematical constrain conditions in forming interference striation pattern are different for individual array element, but it is proved that the differences of time delays between array elements can be used in compensation of beamforming. The theoretical analysis, system simulation and some results of at sea experiment show a new way in passive ranging and target recognition.展开更多
Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inac...Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inaccessibility. Currently, breast cancer and its metastasis are the second leading cause of death among women. Tumor microenvironment and blood brain barrier (BBB) represent great obstacles in targeting breast cancer and its metastasis. Chemotherapy is a safer treatment modality for brain metastasis compared with risky surgical resection and brain radiotherapy. Unfortunately, conventional chemotherapy lack penetration of BBB and suffer from multiple resistance mechanisms. Current treatment technologies for brain metastases of breast cancer have limited long-term success and numerous side effects, illustrating the urgent need for novel smart strategies. Various novel drug entities and nanosystems have been employed to improve diagnosis and targeted treatment of breast cancer and its metastasis. Immunotherapy agents and small tyrosine kinase inhibitors have been shown to reduce tumor size and increase survival in patients with breast cancer, but still poorly penetrate BBB. Tailored sized nanoparticles to some extent crossed brain tumor barrier and enhanced drug accumulation in tumors by taking advantage of enhanced permeability and retention. Furthermore, various active targeting strategies have been adopted to improve accessibility to brain malignancies. Therefore, to achieve enhanced antitumor therapy against ;breast cancer and its brain metastasis, multi-talented delivery systems are urgently needed for optimal treatment. This review focuses on the various active and passive targeting technologies for the treatment of breast cancer brain metastases in the past decade. A comprehensive summary and examples along with pros and cons of each system will be discussed. Different treatment modalities and nanotechnology facilities will be demonstrated to aid in designing the optimal smart, safe, targeted and effective systems to combat brain metastases of breast cancer.展开更多
The method for Bearings-Only Target Motion Analysis (BO-TMA) based on bearing measurements fusion of two arrays is studied. The algorithms of pseudolinear processing, extended Kalman filter and maximum likelihood est...The method for Bearings-Only Target Motion Analysis (BO-TMA) based on bearing measurements fusion of two arrays is studied. The algorithms of pseudolinear processing, extended Kalman filter and maximum likelihood estimation are presented. The results of simulation experiments show that the BO-TMA method based on association of multiple arrays not only makes contributions towards eliminating maneuvers needed by bearings-only TMA based on single array,but also improves the stabilization and global convergence for varied estimation algorithms.展开更多
The special sections of volume target are observed with acoustic vector intensity according to the difference among their radiated-noise characteristics, then three sections are tracked with Kalman filtering, and targ...The special sections of volume target are observed with acoustic vector intensity according to the difference among their radiated-noise characteristics, then three sections are tracked with Kalman filtering, and target size is estimated. Simulation results indicate that in ideal condition three sections of a ship can be tracked and ship's size can be estimated even though one of three sections can not be observed.展开更多
Two target motion analysis (TMA) methods using multi-dimension information are studied, one is TMA with bearing-frequency and the other is TMA with multiple arrays. The optimization algorithm combining Gauss-Newton (G...Two target motion analysis (TMA) methods using multi-dimension information are studied, one is TMA with bearing-frequency and the other is TMA with multiple arrays. The optimization algorithm combining Gauss-Newton (G-N) method with Levenberg-Marquardt (L- M) method is applied to analyze the performance of target tracking with maximum likelihood estimation(MLE), and Monte Carlo experiments are presented. The results show that although the TMA with multi-dimension information have eliminated the maneuvers needed by conven- tional bearing-only TMA, but the application are not of universality展开更多
A new algorithm based on a Supervised Self-Organizing neural network for the pas sive sonar target recognition was proposed. Because of the incompleteness of the passive sonar exemplar set, the algorithm introduced a ...A new algorithm based on a Supervised Self-Organizing neural network for the pas sive sonar target recognition was proposed. Because of the incompleteness of the passive sonar exemplar set, the algorithm introduced a Multi-Activation-function structure and Supervised Self-Organizing competitive learning algorithm into the classic feed-forward neural networks,and obviously improved the generalization ability in target recognition. Besides, it can effi ciently reduce the learning time and avoid the local optimum. The recognition experiments of realistic passive sonar signals show that this new algorithm has good generalization ability and high recognition rate展开更多
Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes (CCNU-Lips) and evaluate its physicochemical properties and the tiss...Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes (CCNU-Lips) and evaluate its physicochemical properties and the tissue targeting after intravenous (i.v.) injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline (pH 6.8) at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin (CCNU-Sol). CCNU-Lips had an average diameter of (189.8±28.5) nm with a zeta potential of (-19.13±0.12) mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life (t1/2β) in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.展开更多
Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisel...Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisely deliver drugs to the inflammatory site,which leads to life-long medication and serious side effects that can adversely impact patients’adherence.It is necessary to construct optimal drug delivery systems(DDSs)that can target drugs to the region of inflammation,thereby improve therapeutic efficacy and reduce side effects.With the burgeoning development of nanotechnology-based nanomedicines(NMs)and prodrug strategy,remarkable progresses in the treatment of IBD have been made in recent years.Herein,the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy.First,the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs.Second,the necessity of NMs for the IBD therapy is elaborated,and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed.Furthermore,the emerging prodrug-based therapeutics are summarized,including 5-aminosalicylic acid-,amino acid-,and carbohydrate-conjugated prodrugs.Finally,the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.展开更多
A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inor...A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3× relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0×) than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4×) than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.展开更多
Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are...Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.展开更多
基金Project(61101186)supported by the National Natural Science Foundation of China
文摘In the tracking problem for the maritime radiation source by a passive sensor,there are three main difficulties,i.e.,the poor observability of the radiation source,the detection uncertainty(false and missed detections)and the uncertainty of the target appearing/disappearing in the field of view.These difficulties can make the establishment or maintenance of the radiation source target track invalid.By incorporating the elevation information of the passive sensor into the automatic bearings-only tracking(BOT)and consolidating these uncertainties under the framework of random finite set(RFS),a novel approach for tracking maritime radiation source target with intermittent measurement was proposed.Under the RFS framework,the target state was represented as a set that can take on either an empty set or a singleton; meanwhile,the measurement uncertainty was modeled as a Bernoulli random finite set.Moreover,the elevation information of the sensor platform was introduced to ensure observability of passive measurements and obtain the unique target localization.Simulation experiments verify the validity of the proposed approach for tracking maritime radiation source and demonstrate the superiority of the proposed approach in comparison with the traditional integrated probabilistic data association(IPDA)method.The tracking performance under different conditions,particularly involving different existence probabilities and different appearance durations of the target,indicates that the method to solve our problem is robust and effective.
文摘For the problem of deterministic parameter estimate, the theoretical lower bound of esti- mate error is the Cramér-Rao bound; while for random parameter, the lower bound of estimate error is generally termed by Posterior Cramér-Rao Bound (PCRB). Under the background of passive tracking where the target's state can be seen as a time-varying random parameter, PCRB of the state estimate error is analyzed in this paper, and the relation between PCRB and varied condition is also fully in- vestigated using different simulation examples. The presented analytical method provides a theoretical base for performance assessment of all kinds of suboptimal estimate algorithms used in practice.
文摘A marginalized particle filtering (MPF) approach is proposed for target tracking under the background of passive measurement. Essentially, the MPF is a combination of particle filtering technique and Kalman filter. By making full use of marginalization, the distributions of the tractable linear part of the total state variables are updated analytically using Kalman filter, and only the lower-dimensional nonlinear state variable needs to be dealt with using particle filter. Simulation studies are performed on an illustrative example, and the results show that the MPF method leads to a significant reduction of the tracking errors when compared with the direct particle implementation. Real data test results also validate the effectiveness of the presented method.
基金Supported by the National Basic Research Program of China(No.2009CB930102)the National High Technology Research and Development Program of China(No.2007AA03Z535)+3 种基金the National Natural Science Foundation of China(No.21004062)the China-Japan-Korea Foresight Program(No.20621140369)"100 Talents Program" of the Chinese Academy of Sciences(No.KGCX2- YW-802) the Project of Jilin Provincial Science & Technology Department,China(No.200705110)
文摘Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG:poly(ethylene glycol);LA:L-lactide;DHP:2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-micelles) was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P(LA-co-DHP) followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P(LA-co-DHP) was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc(ZnEt2) as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM(transmission electron microscope) or 80 nm by DLS(dynamic light scattering).Their in vitro cell uptake experiment by CLSM(confocal laser scanning microscopy) and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration(fluorescent intensity) in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.
文摘Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcutaneous form.Treatment of VL includes chemotherapeutic agents which are associated with some major hurdles like toxicities,parenteral administration,high cost,parasite resistance and stability.Hence,there is an urgent requirement to develop novel chemotherapeutic agents or repurposing of existing drugs against VL.Developing formulation of new chemical entity for the treatment of VL is laborious,time consuming and associated with huge financial burden.However,screening of existing chemotherapeutic agents is a good alternative to avail cost-effective treatment option for VL.Non-PEGylated liposome encapsulated doxorubicin(Myocet®)is proposed as an alternative treatment option for VL in this review article.Here,we covered the fundamental aspects of VL,loophole associated with available current treatment strategies and non-PEGylated liposome encapsulated doxorubicin as a novel alternative formulation for treating VL,as this liposomal delivery system of doxorubicin might passively target the intra-cellular regions of macrophage.
文摘In the state estimation of passive tracking systems, the traditional approximate expression for the Cramero-Rao lower bound (CRLB) does not take two factors into consideration, that is, measurement origin uncertainty aad state noise. Such treatment is only valid in ideal situation but it is not feasible in actual situation. In this article, considering the two factors, the posterior Cramer-Rao lower bound (PCRLB) recursion expression for the error of bearing-only tracking is derived. Then, further analysis is carried out on the PCRLB. According to the final result, there are four main parameters that play a role in the performance of the PCRLB, that is, measurement noise, detection probability, state noise and clutter density, amongst which the first two have greater impact on the performance of the PCRLB than the others.
文摘The study of wave guide invariant in underwater acoustics is one of attracted topics in recent 30 years. The interferences of direct wave and reflect wave from sea surface and sea bottom of underwater target radiated noise inherent the information of target distance. Extraction of these distance information will provide a possible new way in passive ranging for underwater target. The theoretical analysis and the results of at sea experiments show that the LOFAR (Low Frequency Analysis Record) figure inherently contains the range and moving information of passive acoustic sources, even in the situation that the receiver is only one single hydrophone. The theoretical analysis of extraction of target distance information by using wave guide invariant is presented in this paper. It is shown that, based on the interference striation pattern of target, the hydrophone array system is possible to extract the distance information with quite high array gain. Although the mathematical constrain conditions in forming interference striation pattern are different for individual array element, but it is proved that the differences of time delays between array elements can be used in compensation of beamforming. The theoretical analysis, system simulation and some results of at sea experiment show a new way in passive ranging and target recognition.
文摘Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inaccessibility. Currently, breast cancer and its metastasis are the second leading cause of death among women. Tumor microenvironment and blood brain barrier (BBB) represent great obstacles in targeting breast cancer and its metastasis. Chemotherapy is a safer treatment modality for brain metastasis compared with risky surgical resection and brain radiotherapy. Unfortunately, conventional chemotherapy lack penetration of BBB and suffer from multiple resistance mechanisms. Current treatment technologies for brain metastases of breast cancer have limited long-term success and numerous side effects, illustrating the urgent need for novel smart strategies. Various novel drug entities and nanosystems have been employed to improve diagnosis and targeted treatment of breast cancer and its metastasis. Immunotherapy agents and small tyrosine kinase inhibitors have been shown to reduce tumor size and increase survival in patients with breast cancer, but still poorly penetrate BBB. Tailored sized nanoparticles to some extent crossed brain tumor barrier and enhanced drug accumulation in tumors by taking advantage of enhanced permeability and retention. Furthermore, various active targeting strategies have been adopted to improve accessibility to brain malignancies. Therefore, to achieve enhanced antitumor therapy against ;breast cancer and its brain metastasis, multi-talented delivery systems are urgently needed for optimal treatment. This review focuses on the various active and passive targeting technologies for the treatment of breast cancer brain metastases in the past decade. A comprehensive summary and examples along with pros and cons of each system will be discussed. Different treatment modalities and nanotechnology facilities will be demonstrated to aid in designing the optimal smart, safe, targeted and effective systems to combat brain metastases of breast cancer.
文摘The method for Bearings-Only Target Motion Analysis (BO-TMA) based on bearing measurements fusion of two arrays is studied. The algorithms of pseudolinear processing, extended Kalman filter and maximum likelihood estimation are presented. The results of simulation experiments show that the BO-TMA method based on association of multiple arrays not only makes contributions towards eliminating maneuvers needed by bearings-only TMA based on single array,but also improves the stabilization and global convergence for varied estimation algorithms.
基金This work was supported by the fund of special doctoral site fund of National education ministry.
文摘The special sections of volume target are observed with acoustic vector intensity according to the difference among their radiated-noise characteristics, then three sections are tracked with Kalman filtering, and target size is estimated. Simulation results indicate that in ideal condition three sections of a ship can be tracked and ship's size can be estimated even though one of three sections can not be observed.
文摘Two target motion analysis (TMA) methods using multi-dimension information are studied, one is TMA with bearing-frequency and the other is TMA with multiple arrays. The optimization algorithm combining Gauss-Newton (G-N) method with Levenberg-Marquardt (L- M) method is applied to analyze the performance of target tracking with maximum likelihood estimation(MLE), and Monte Carlo experiments are presented. The results show that although the TMA with multi-dimension information have eliminated the maneuvers needed by conven- tional bearing-only TMA, but the application are not of universality
文摘A new algorithm based on a Supervised Self-Organizing neural network for the pas sive sonar target recognition was proposed. Because of the incompleteness of the passive sonar exemplar set, the algorithm introduced a Multi-Activation-function structure and Supervised Self-Organizing competitive learning algorithm into the classic feed-forward neural networks,and obviously improved the generalization ability in target recognition. Besides, it can effi ciently reduce the learning time and avoid the local optimum. The recognition experiments of realistic passive sonar signals show that this new algorithm has good generalization ability and high recognition rate
文摘Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes (CCNU-Lips) and evaluate its physicochemical properties and the tissue targeting after intravenous (i.v.) injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline (pH 6.8) at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin (CCNU-Sol). CCNU-Lips had an average diameter of (189.8±28.5) nm with a zeta potential of (-19.13±0.12) mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life (t1/2β) in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.
基金supported by National Key R&D Program of China(No.2021YFA0909900)National Natural Science Foundation of China(No.81773656)+3 种基金Liaoning Revitalization Talents Program(No.XLYC1808017)Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454)China Postdoctoral Science Foundation(No.2020M680986)General Project of Liaoning Provincial Department of Education(Nos.LKZ0927 and LJKQZ2021034)。
文摘Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisely deliver drugs to the inflammatory site,which leads to life-long medication and serious side effects that can adversely impact patients’adherence.It is necessary to construct optimal drug delivery systems(DDSs)that can target drugs to the region of inflammation,thereby improve therapeutic efficacy and reduce side effects.With the burgeoning development of nanotechnology-based nanomedicines(NMs)and prodrug strategy,remarkable progresses in the treatment of IBD have been made in recent years.Herein,the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy.First,the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs.Second,the necessity of NMs for the IBD therapy is elaborated,and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed.Furthermore,the emerging prodrug-based therapeutics are summarized,including 5-aminosalicylic acid-,amino acid-,and carbohydrate-conjugated prodrugs.Finally,the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.
文摘A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3× relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0×) than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4×) than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.
基金partially supported by grants from the National Natural Science Foundation of China (No.31971302,China)the Natural Science Foundation of Guangdong Province of China (No.2019A1515011597,China)+2 种基金the talent young scientist supporting program of China Association for Science and Technologythe Educational Commission of Guangdong Province of China Key Project (No.2020ZDZX2001,China)the joint grant between Guangzhou City and College (No.202102010106,China)。
文摘Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.