查看更多>>摘要：Tumor vasculature is characterized by aberrant structure and function,resulting in immune suppressive profiles of tumor microenvironment through limiting immune cell infiltration into tumors,endogenous immune surveillance and immune cell function.Vascular normalization as a novel therapeu-tic strategy tends to prune some of the immature blood vessels and fortify the structure and function of the remaining vessels,thus improving immune stimulation and the efficacy of immunotherapy.Interestingly,the presence of"immune-vascular crosstalk"enables the formation of a positive feedback loop between vascular normalization and immune reprogramming,providing the possibility to develop new cancer ther-apeutic strategies.The applications of nanomedicine in vascular-targeting therapy in cancer have gained increasing attention due to its specific physical and chemical properties.Here,we reviewed the recent advances of effective routes,especially nanomedicine,for normalizing tumor vasculature.We also sum-marized the development of enhancing nanoparticle-based anticancer drug delivery via the employment of transcytosis and mimicking immune cell extravasation.This review explores the potential to optimize nanomedicine-based therapeutic strategies as an alternative option for cancer treatment.
查看更多>>摘要：As one of the most serious threats to human being,cancer is hard to be treated when metas-tasis happens.What's worse,there are few identified targets of metastasis for drug development.There-fore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are dis-cussed.
Yuefei ZhuXiangrong YuSoracha D. ThamphiwatanaYing Zheng...
2054-2074页
查看更多>>摘要：Cancer immunotherapy has veered the paradigm of cancer treatment.Despite recent ad-vances in immunotherapy for improved antitumor efficacy,the complicated tumor microenvironment(TME)is highly immunosuppressive,yielding both astounding and unsatisfactory clinical successes.In this regard,clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME.Various advanced designs of nanomedicines could still not fully surmount the de-livery barriers of the TME.The immunosuppressive TME may even dampen the efficacy of antitumor immunity.Recently,some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment(TIME)for robust immunothera-peutic responses.In this review,we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy,especially those unique classes associated with the immunosuppressive effect.The immunoregulatory cell types in-side the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation.After introducing the various strategies,we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nano-medicines.
Nitin Bharat CharbeNikhil D. AmnerkarB. RameshMurtaza M. Tambuwala...
2075-2109页
查看更多>>摘要：In many ways,cancer cells are different from healthy cells.A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells.Currently,nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells.This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells.It also provides the necessary information about siRNA develop-ment and its mechanism of action.Overall,this review gives us a clear picture of lipid and polymer-based drug delivery systems,which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
查看更多>>摘要：The complex tumor microenvironment is a most important factor in cancer development.The biological microenvironment is composed of a variety of barriers including the extracellular matrix and associated cells such as endothelia cells,pericytes,and cancer-associated fibroblasts.Different strategies can be utilized to enhance nanoparticle-based drug delivery and distribution into tumor tissues addressing the extracellular matrix or cellular components.In addition to the biological microenvironment,the immunological conditions around the tumor tissue can be very complicated and cancer cells have various ways of evading immune surveillance.Nanoparticle drug delivery systems can enhance cancer immuno-therapy by tuning the immunological response and memory of various immune cells such as T cells,B cells,macrophages,and dendritic cells.In this review,the main components in the tumor biological and immunological environment are discussed.The focus is on recent advances in nanoparticle-based drug delivery systems towards targets within the tumor microenvironment to improve cancer chemotherapy and immunotherapy.
查看更多>>摘要：Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interfer-ence strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treat-ment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted stra-tegies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.
查看更多>>摘要：Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic resistance.Current treatment prescriptions for desmoplastic tumors are usu-ally not sufficient to eliminate the malignancy.Recently,through modulating cancer-associated fibro-blasts(CAFs)which are the most abundant cell type among all stromal cells,natural products have improved chemotherapies and the delivery of nanomedicines to the tumor cells,showing promising abil-ity to improve treatment effects on desmoplastic tumors.In this review,we discussed the latest advances in inhibiting desmoplastic tumors by modeling CAFs using natural products,highlighting the potential therapeutic abilities of natural products in targeting CAFs for cancer treatment.
查看更多>>摘要：Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(Ml)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of Ml,M2 exerts anti-inflammatory and tumori-genic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progres-sion.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
查看更多>>摘要：Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand 16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cell-based immunotherapy for liver cancer.However,abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control.Taking advantage of the intrinsic property of LSECs in capturing circulating nano-particles in the circulation,we proposed a strategy using nanoemulsion-loaded obeticholic acid(OCA),a clinically approved selective farnesoid X receptor(FXR)agonist,for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy.The OCA-nanoemulsion(OCA-NE)was pre-pared via ultrasonic emulsification method,with a diameter of 184 nm and good stability.In vivo bio-distribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer cells.As a result,OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model,which performed much better than oral medica-tion of free OCA.Immunologic analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-y,as well as increased NKT cell populations inside the tumor.Overall,our research provides a new evidence for the antitumor effect of receptors for primary bile acids,and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy
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