Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Development and Evaluation of 3D Delivery Animation Software Designed to Improve the Mother’s and Spouse’s Satisfaction with Delivery

Purpose: To clarify the effectiveness of 3-D delivery animation software for the mother’s and husband’s satisfaction with delivery. Subjects and Method: We independently developed a software application used to display the pelvic region and explain the labor process. The study involved a collaboration with hospital staff who recruited 18 primiparous and 18 multiparous mothers who were hospitalized for delivery at Facility A. The midwife explained the process of delivery using the “Delivery Animation Software”. A self-administered, anonymous questionnaire was distributed and analyzed separately for primiparous and multiparous mothers and their husbands. Results: 1) For both primiparous and multiparous couples, both mothers and their husbands gained a significantly higher level of understanding after delivery than during pregnancy. 2) The Self-Evaluation Scale for Experience of Delivery results were as follows: “I did my best for the baby even if it was painful” was selected more often for “birth coping skills”;“reliable medical staff” was selected more often for “physiological birth process”;“the birth progressed as I expected” was selected frequently by primiparous mothers;and “the birth progressed smoothly” was selected often by multiparous mothers. 3) In terms of husbands’ satisfaction with the delivery, “I was satisfied with the delivery”, “I was given an easy-to-understand explanation”, and “They explained the process to me” was selected of primiparous and multiparous fathers. 4) All primiparous and multiparous mothers positively evaluated whether the delivery animation was helpful in understanding the process of delivery. Conclusion: The delivery animation was effective in improving the understanding and satisfaction of both the mothers and their husbands.

Determinants of Home Deliveries by Pregnant Mothers in Lumbo Chabbobboma Zone of Gwembe District in Zambia

Background: Home deliveries is still high globally at 42% WHO 2022, due to high home deliveries, maternal death is also high at 43% globally. In sub-Sahara region home deliveries still high. Giving birth at health facilities in most of sub-Saharan African countries Zambia inclusive is still a challenge whereby more than 51% of first-time mothers give birth at home and this gives a risk of high maternal and perinatal deaths. Therefore Reducing number of home deliveries is important to improve maternal and perinatal health issues. In this study, the aim was to investigate the determinants of home deliveries by pregnant mothers in the Luumbo zone of Gwembe district, Zambia. Purpose: Access to skilled care and facilities with capacity to provide emergency and newborn care is critical to reduce maternal death. In Zambia 42% of women still deliveries from home, suggesting a persistent challenge for women to seek, reach, and receive quality maternity care. This study aimed investigate the determinants of home deliveries by pregnant mothers in Luumbo zone of Gwembe district, Zambia. Methods: The study was conducted among postnatal mothers who came for postnatal care at 6 weeks in Luumbo Chabbobboma clinic in Gwembe district southern province of Zambia. This was a descriptive cross-sectional study where a Simple random sampling technique was used to select 105 women of childbearing age who attended postnatal and had a recent delivery. Data were collected using a researcher-administered structured questionnaire to identify determinants of home deliveries in Luumbo Chabbobboma zone. Data analysis was done using SPSS computer software version 27.0. Both descriptive and inferential (chi-square test) analyses were performed and statistical significance was taken at α ≤ 0.05. Results: The results show that 46 (43.8%) respondents were in the age bracket 20 - 29 years. Of the 105 respondents included in the study, 24 (22.9%) of them delivered from home. The results show that high maternal age (p = 0.03), occupation (p = 0.024), distance to the facility (p = 0.014), means of transportation (p = 0.023), multiparity (p = 0.01), timing and number of ANC visits (p Conclusion: From this population. The major reason why women still deliver at home was long distance to the nearest facility. To reduce maternal and perinatal mortality access to health facilities by pregnant women needs to be improved. There should also be active engagement of the traditional and religious institutions in the area.

Prevalence, Maternal and Perinatal Prognosis of Breech Delivery Compared to That of the Vertex in 242 Cases for 484 Controls at Ségou Hospital in Malti

Introduction: Breech birth has always been a subject of great interest because of its risks of perinatal morbidity and mortality. Aim: The aim of our study was to compare the maternal and perinatal prognosis of breech delivery with that of vertex delivery. Patients and Method: This was a retrospective case-control analytical study carried out in the obstetrics and gynaecology department of Ségou hospital over a 2-year period from 1 January 2020 to 31 December 2021, involving 242 breech deliveries compared with 484 top deliveries with a live single foetus without foetal malformation of gestational age ≥ 35 SA. The statistical tests used were: chi² (p Results: The frequency of breech delivery was 3.3%, with a predominance of caesarean section for breech presentation (64.88%) compared with 32.85% for vertex (P: 0.00;CI: (0.191 - 0.367). The perinatal prognosis of fetuses with breech presentations was marked by a higher rate of neonatal asphyxia (Apgar score Conclusion: Breech birth is relatively rare in our department. It carries a higher risk of maternal morbidity and neonatal morbidity than breech delivery. However, the vital prognosis for the mother was identical in both groups.

Digital twin driven and intelligence enabled content delivery in end-edge-cloud collaborative 5G networks

The rapid development of 5G/6G and AI enables an environment of Internet of Everything(IoE)which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay.However,these massive devices will lead to explosive traffic growth,which in turn cause great burden for the data transmission and content delivery.This challenge can be eased by sinking some critical content from cloud to edge.In this case,how to determine the critical content,where to sink and how to access the content correctly and efficiently become new challenges.This work focuses on establishing a highly efficient content delivery framework in the IoE environment.In particular,the IoE environment is re-constructed as an end-edge-cloud collaborative system,in which the concept of digital twin is applied to promote the collaboration.Based on the digital asset obtained by digital twin from end users,a content popularity prediction scheme is firstly proposed to decide the critical content by using the Temporal Pattern Attention(TPA)enabled Long Short-Term Memory(LSTM)model.Then,the prediction results are input for the proposed caching scheme to decide where to sink the critical content by using the Reinforce Learning(RL)technology.Finally,a collaborative routing scheme is proposed to determine the way to access the content with the objective of minimizing overhead.The experimental results indicate that the proposed schemes outperform the state-of-the-art benchmarks in terms of the caching hit rate,the average throughput,the successful content delivery rate and the average routing overhead.

Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

Delivering Microrobots in the Musculoskeletal System

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo end-stage surgery.Therefore,future treatments should focus on early detection and intervention of regional lesions.Microrobots have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted delivery.Through the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for treatment.In the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body.Compared to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/drugs.This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system.We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

Enhancing Private Healthcare Effectiveness in Lagos State, Nigeria: An Overview of the Effect of Quality Improvement Initiatives and Implications for Sustainable Healthcare Delivery

Background: Nigeria, a nation grappling with rapid population growth, economic intricacies, and complex healthcare challenges, particularly in Lagos State, the economic hub and most populous state, faces the challenge of ensuring quality healthcare access. The overview of the effect of quality improvement initiatives in this paper focuses on private healthcare providers in Lagos State, Nigeria. The study assesses the impact of donor-funded quality improvement projects on these private healthcare facilities. It explores the level of participation, perceived support, and tangible effects of the initiatives on healthcare delivery within private healthcare facilities. It also examines how these initiatives influence patient inflow and facility ratings, and bring about additional benefits and improvements, provides insights into the challenges faced by private healthcare providers in implementing quality improvement projects and elicits recommendations for improving the effectiveness of such initiatives. Methods: Qualitative research design was employed for in-depth exploration, utilizing semi-structured interviews. Private healthcare providers in Lagos involved in the SP4FP Quality Improvement Project were purposively sampled for diversity. Face-to-face interviews elicited insights into participation, perceived support, and project effects. Questions covered participation levels, support perception, changes observed, challenges faced, and recommendations. Thematic analysis identified recurring themes from interview transcripts. Adherence to ethical guidelines ensured participant confidentiality and informed consent. Results: Respondents affirmed active involvement in the SP4FP Quality Improvement Project, echoing literature emphasizing private-sector collaboration with the public sector. While acknowledging positive influences on facility ratings, respondents highlighted challenges within the broader Nigerian healthcare landscape affecting patient numbers. Respondents cited tangible improvements, particularly in staff management and patient care processes, validating the positive influence of quality improvement projects. Financial constraints emerged as a significant challenge, aligning with existing literature emphasizing the pragmatic difficulties faced by private healthcare providers. Conclusions: This study illuminates the complex landscape of private healthcare provision in Lagos State, emphasizing the positive impact of donor-funded quality improvement projects. The findings provide nuanced insights, guiding policymakers, healthcare managers, and practitioners toward collaborative, sustainable improvements. As Nigeria progresses, these lessons will be crucial in shaping healthcare policies prioritizing population well-being.

A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

A Proposed Approach for Measuring Maturity Level of Software Delivery

Software delivery is vital for modern organizations, driving innovation and competitiveness. Measuring an organization’s maturity in software delivery is crucial for efficiency and quality. The Capability Maturity Model (CMM) framework provides a roadmap for improvement but assessing an organization’s CMM Level is challenging. This paper offers a quantitative approach tailored to the CMM framework, using Goal-Question-Metric (GQM) frame-works for each key process area (KPA). These frameworks include metrics and questions to compute maturity scores effectively. The study also refines practices into questions for a thorough assessment. The result is an Analysis Matrix that calculates weighted scores and an overall maturity score. This approach helps organizations assess and enhance their software delivery processes systematically, aiming for improved practices and growth.

Microgels for Cell Delivery in Tissue Engineering and Regenerative Medicine

Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels can also be aggregated into microporous scaffolds,promoting cell infiltration and proliferation for tissue repair.This review gives an overview of recent developments in the fabrication techniques and applications of microgels.A series of conventional and novel strategies including emulsification,microfluidic,lithography,electrospray,centrifugation,gas-shearing,three-dimensional bioprinting,etc.are discussed in depth.The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy.Additionally,we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering.Through stimulating innovative ideas,the present review paves new avenues for expanding the application of microgels in cell delivery techniques.

Epidemiological Aspects of Stillbirth and Neonatal Deaths in the Delivery Room at the Libreville Mother-Child University Hospital from 2019 to 2022

Introduction: Stillbirths are estimated at 2 million each year, of which more than 40% occur during labour. Our objective was to study the epidemiological aspects of stillbirth and neonatal deaths in the delivery room in our health facility. Patients and methods: Prospective, descriptive and analytical study, conducted at the Jeanne Ebori Foundation Mother-Child University Hospital over 4 years (January 2019-December 2022). All neonatal deaths in the delivery room or foetal death in utero, were included. Results: Among the 18,346 deliveries performed, 512 newborns were declared dead in the delivery room (27.9‰ live births), divided into in utero foetal death (19.0‰) and immediate neonatal death (8.9‰). The mean age was 34.3 weeks of amenorrhea. The rate of preterm birth was 60.4%. The sex ratio was 1.1. The average weight was 2186.6. The main causes were vascular (46.1%), foetal (20.2%), adnexal (17.1%) and asphyxia per partum (16.6%). Foetal causes were more likely to result in IUFD than other causes (OR = 6.4 [2.4 - 15.7], p < 0.001). After birth, partum asphyxia was more likely to lead to death before 15 minutes of life than other causes (OR = 11 [6.1 - 18.9], p Conclusion: The causes of stillbirth and early neonatal mortality are dominated by maternal vascular pathologies. However, the proportion of childbirth-related causes remains worrying. Better monitoring of pregnancy and labour will minimize this prevalence in our hospital.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

The Diagnostic Validity of Preterm Delivery in Adolescent Girls Based on Neonatal Clinical Assessment

Introduction: Pregnant adolescents are at an elevated risk of premature delivery. In the context of low levels of education and limited resources, several difficulties are encountered in determining gestational age. These include a lack of knowledge of the date of the last menstrual period, failure to perform first-trimester ultrasound, and absence of an electroencephalogram. In such circumstances, the utilisation of a morphological score, analogous to the Finnstrom score, to ascertain gestational age would appear to be a more accessible and straightforward approach. This study aimed to assess the accuracy of the Finnström score in newborns of teenage mothers, where the date of the last menstrual period may be subject to inaccuracy, in order to validate the diagnosis of preterm delivery. Methods: This was an analytical cross-sectional design of 87 newborns of teenage mothers, multicenter, conducted in the city of Kisangani, Democratic Republic of the Congo (DRC) with prospective data collection. Results: This study involved 87 newborns born to adolescent mothers. The incidence of premature delivery, as determined by the date of the last menstrual period, was observed to be 17.6% among teenage girls and 5.3% among adults. As indicated by the Finnström morphological score and early ultrasound dating, the incidence of preterm delivery was notably elevated, at 32.2% and 37.7%, respectively. The correlation between gestational age according to the date of the last menstrual period and gestational age according to early ultrasound dating was low (0.338), while there was a satisfactory correlation between gestational age according to the Finnström morphological score and early ultrasound dating (0.828). Conclusion: The Finnström morphological score represents a valuable tool for accurately determining gestational age, thereby validating the diagnosis of preterm delivery in adolescents, who are prone to inaccuracies in determining the date of the last menstrual period. It is therefore recommended that this score be evaluated in our setting, where access to ultrasound is sometimes still problematic.

Preparation and Characterization of pH-Responsive Charge Reversal Nanocomposite for miRNA Delivery

pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.

The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Factors Influencing Mode of Delivery: A Case-Control Study

The primary objective of this investigation was to scrutinize the prepregnancy conditions and lifestyles of 2046 women residing in Liuzhou City, with the aim of delineating the determinants of delivery methods. Evidently, the study unearthed substantial correlations between prepregnancy body mass index, educational attainment, exposure to passive smoking, medical history, and other variables with the mode of delivery. Furthermore, a predictive nomogram model was formulated to accurately forecast the likelihood of cesarean section. These discernments equip pertinent authorities with the means to institute targeted screening and supportive measures for women contemplating pregnancy based on these identified factors. Moreover, provision of services such as prepregnancy counseling and clinical risk assessments could be instrumental in curbing the incidence of cesarean section.

Postpartum Quality of Life in Primiparous Women after Normal Vaginal Delivery versus Caesarean Section

Background: Studies on either postnatal quality of life in general or studies that compare quality of life in new mothers after different mode of delivery are limited. An investigation on health related quality of life measures in women after different type of delivery showed that women who had vaginal delivery had better health related quality of life compared to those who had caesarean section. However, the best method of delivery, vaginal or caesarean for postpartum quality of life is a difficult question as it is a matter of controversy both from professional’s perspectives and from women’s experience during childbirth. Objective: To compare postpartum quality of life in primiparous women after vaginal delivery versus caesarean section. Methods: Prospective cross-sectional study was conducted at the department of Obstetrics and Gynecology, Salmaniya medical complex in Kingdom of Bahrain. 500 primiparous women who gave birth either vaginally or by cesarean section answered a questionnaire designed to include general information, questions from short form health survey questionnaire (SF-36) and specific questions regarding postnatal related symptoms. Results: Body pain, fatigue, wound pain, headache and backache were significantly higher in cesarean section group as compared to vaginal delivery group (p-value Conclusion: Cesarean delivery has negatively affected the quality of life (QOL) of primiparous women. More studies with larger sample sizes should be conducted to examine the effects of cesarean delivery on QOL in both primiparous and multiparas within a shorter period after delivery. .

Obstetric Anesthesia Practice Significantly Evolved: A Field for Cesarean Delivery Parturient for the Provision of Safe Anesthesia in Urgent Circumstances

General anesthesia and Obstetric Anesthesia is the gold standard for a cesarean section but there are some cases where general anesthesia is unavoidable. The use of general anesthesia for cesarean delivery has decreased in recent years due to the widespread use of neuraxial techniques. The choice of anesthesia techniques for cesarean delivery depends on several factors, including the patient’s psychology and the attending physician’s experience. It is chosen because of its safety profile and its benefits to the mother and fetus. It may be indicated due to emergency, maternal refusal of regional techniques, or regional contraindications. Major complications include failed intubation, gastric content aspiration, and increased bleeding risk. This study aims to evaluate the impact of a newly launched team on obstetric anesthesia practice.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.