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亚洲药物制剂科学(英文版)
亚洲药物制剂科学(英文版)

双月刊

1818-0876

亚洲药物制剂科学(英文版)/Journal Asian Journal of Pharmaceutical SciencesSCI
正式出版
收录年代

    Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy

    Yu HuangHui FanHuihui Ti
    1-37页
    查看更多>>摘要：With the rapid development of the fields of tumor biology and immunology,tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential,particularly for treating tumors that do not respond to standard treatment options.Despite its advances,immunotherapy still has limitations,such as poor clinical response rates and differences in individual patient responses,largely because tumor tissues have strong immunosuppressive microenvironments.Many tumors have a tumor microenvironment(TME)that is characterized by hypoxia,low pH,and substantial numbers of immunosuppressive cells,and these are the main factors limiting the efficacy of antitumor immunotherapy.The TME is crucial to the occurrence,growth,and metastasis of tumors.Therefore,numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME.Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy.The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy.However,the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects.Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting.Importantly,they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells.Therefore,nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy.Therefore,this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.
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    Ionic liquids as the effective technology for enhancing transdermal drug delivery:Design principles,roles,mechanisms,and future challenges

    Xuejun ChenZiqing LiChunrong YangDegong Yang...
    38-51页
    查看更多>>摘要：Ionic liquids(ILs)have been proven to be an effective technology for enhancing drug transdermal absorption.However,due to the unique structural components of ILs,the design of efficient ILs and elucidation of action mechanisms remain to be explored.In this review,basic design principles of ideal ILs for transdermal drug delivery system(TDDS)are discussed considering melting point,skin permeability,and toxicity,which depend on the molar ratios,types,functional groups of ions and inter-ionic interactions.Secondly,the contributions of ILs to the development of TDDS through different roles are described:as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients(API-ILs)for regulating skin permeability,solubility,release,and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials.Moreover,diverse action mechanisms,mainly including the interactions among ILs,drugs,polymers,and skin components,are summarized.Finally,future challenges related to ILs are discussed,including underlying quantitative structure-activity relationships,complex interaction forces between anions,drugs,polymers and skin microenvironment,long-term stability,and in vivo safety issues.In summary,this article will promote the development of TDDS based on ILs.
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    Targeting the organelle for radiosensitization in cancer radiotherapy

    Xiaoyan SunLinjie WuLina DuWenhong Xu...
    52-71页
    查看更多>>摘要：Radiotherapy is a well-established cytotoxic therapy for local solid cancers,utilizing high-energy ionizing radiation to destroy cancer cells.However,this method has several limitations,including low radiation energy deposition,severe damage to surrounding normal cells,and high tumor resistance to radiation.Among various radiotherapy methods,boron neutron capture therapy(BNCT)has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue,but it remains deficient in terms of insufficient boron accumulation as well as short retention time,which limits the curative effect.Recently,a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy,thereby reducing side effects of normal tissue damage,overcoming radioresistance,and improving radiosensitivity.In this review,we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers,specifically including nucleus,mitochondria,endoplasmic reticulum and lysosomes.Furthermore,the organelle-targeted boron carriers used in BNCT are particularly presented.Through demonstrating recent developments in organelle-targeted radiosensitization,we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.
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    Platelet-derived microparticles and their cargos:The past,present and future

    Jingwen GuoBufeng CuiJie ZhengChang Yu...
    72-88页
    查看更多>>摘要：All eukaryotic cells can secrete extracellular vesicles,which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes.Platelets form platelet-derived microparticles(PMPs)in response to activation,injury,or apoptosis.This review introduces the origin,pathway,and biological functions of PMPs and their importance in physiological and pathological processes.In addition,we review the potential applications of PMPs in cancer,vascular homeostasis,thrombosis,inflammation,neural regeneration,biomarkers,and drug carriers to achieve targeted drug delivery.In addition,we comprehensively report on the origin,biological functions,and applications of PMPs.The clinical transformation,high heterogeneity,future development direction,and limitations of the current research on PMPs are also discussed in depth.Evidence has revealed that PMPs play an important role in cell-cell communication,providing clues for the development of PMPs as carriers for relevant cell-targeted drugs.The development history and prospects of PMPs and their cargos are explored in this guidebook.
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    Edaravone-loaded poly(amino acid)nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

    Yunhan ZhangZhulin ZouShuang LiuFangfang Chen...
    89-101页
    查看更多>>摘要：Neurological injury caused by ischemic stroke is a major cause of permanent disability and death.The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier(BBB)permeability.For that,an edaravone-loaded pH/glutathione(pH/GSH)dual-responsive poly(amino acid)nanogel(NG/EDA)was developed to improve the neuroprotection of EDA.The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments,which enabled the selective and sustained release of EDA at the site of ischemic injury.NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3±8.2 nm.NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion(pMCAO)mice,showing an efficient BBB crossing feature.Notably,NG/EDA with 50 pM EDA significantly increased neuron survival(29.3％)following oxygen and glucose deprivation by inhibiting ferroptosis.In addition,administering NG/EDA for 7 d significantly reduced infarct volume to 22.2％±7.2％and decreased neurobehavioral scores from 9.0±0.6 to 2.0±0.8.Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
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    In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

    Shengnan HuangChenyang ZhouChengzhi SongXiali Zhu...
    102-119页
    查看更多>>摘要：Postoperative tumor recurrence remains a predominant cause of treatment failure.In this study,we developed an in situ injectable hydrogel,termed MPB-NO@DOX+ATRA gel,which was locally formed within the tumor resection cavity.The MPB-NO@DOX+ATRA gel was fabricated by mixing a thrombin solution,a fibrinogen solution containing all-trans retinoic acid(ATRA),and a Mn/NO-based immune nano-activator termed MPB-NO@DOX.ATRA promoted the differentiation of cancer stem cells,inhibited cancer cell migration,and affected the polarization of tumor-associated macrophages.The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+and produce O2,resulting in the release of doxorubicin(DOX).The released DOX entered the nucleus and destroyed DNA,and the fragmented DNA cooperated with Mn2+to activate the cGAS-STING pathway and stimulate an anti-tumor immune response.In addition,when MPB-NO@DOX was exposed to 808 nm laser irradiation,the Fe-NO bond was broken to release NO,which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment.In conclusion,the MPB-NO@DOX+ATRA gel exhibited excellent anti-tumor efficacy.The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
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    Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons

    Xiaomei WuRenxiang YuanYichong XuKai Wang...
    120-135页
    查看更多>>摘要：The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression.Peptide drugs,such as exenatide(Exe),with potential disease-modifying efficacy,have difficulty in crossing the blood-brain barrier(BBB)due to their large molecular weight.Herein,we fabricate multi-functionalized lipid nanoparticles(LNP)Lpc-BoSA/CSO with BBB targeting,permeability-increasing and responsive release functions.Borneol is chemically bonded with stearic acid and,as one of the components of Lpc-BoSA/CSO,is used to increase BBB permeability.Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma,and the amount is 4.21 times greater than that of conventional LNP.Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved,and the content of dopamine is 1.85 times(substantia nigra compacta)and 1.49 times(striatum)that of PD mice.α-Synuclein expression and Lewy bodies deposition are reduced to 51.85％and 44.72％of PD mice,respectively.Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41％.Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway,and effectively prevent the progressive deterioration of Parkinson's disease.In summary,Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.
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    Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

    Xiaoju GuoXiaoxiao ChenJiayi DingFeng Zhang...
    136-152页
    查看更多>>摘要：Chemotherapy plays a crucial role in triple-negative breast cancer(TNBC)treatment as it not only directly kills cancer cells but also induces immunogenic cell death.However,the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment.Herein,we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin(DOX),hemoglobin(Hb)and CaCO3 by a CaCO3-assisted emulsion method,aiming at the effective treatment of TNBC.We found that the obtained nanomedicine(DHCaNPs)exhibited effective drug encapsulation and pH-responsive drug release behavior.Moreover,DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport.Consequently,DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment(TME)by depleting lactic acid,thereby effectively overcoming the resistance to chemotherapy.Furthermore,DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells,therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1(αPD-L1)immunotherapy.In summary,this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME,offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.
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    Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy:Combined sialic acid-modified liposomes with scaffold-based vaccines

    Cong LiLihong WangKexin ZhangZeyu Wang...
    153-169页
    查看更多>>摘要：Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis.However,inflammatory neutrophils,recruited to the postoperative tumor site,have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines.Consequently,addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes.This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine(S-CV)and a sialic acid(SA)-modified,doxorubicin(DOX)-loaded liposomal platform(DOX@SAL).The S-CV contains whole tumor lysates as antigens and imiquimod(R837,Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer,which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation.When administered intravenously,DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo,mitigating neutrophil infiltration and suppressing postoperative inflammatory responses.In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL,a combined chemo-immunotherapeutic strategy,has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression,with minimal systemic toxicity,providing a new concept for postoperative treatment of tumors.
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    Targeted anti-cancer therapy:Co-delivery of VEGF siRNA and Phenethyl isothiocyanate(PEITC)via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

    Bao LiHaoran NiuXiaoyun ZhaoXiaoyu Huang...
    170-187页
    查看更多>>摘要：Anti-tumor angiogenesis therapy,targeting the suppression of blood vessel growth in tumors,presents a potent approach in the battle against cancer.Traditional therapies have primarily concentrated on single-target techniques,with a specific emphasis on targeting the vascular endothelial growth factor,but have not reached ideal therapeutic efficacy.In response to this issue,our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs.These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes.To enhance their targeted delivery capability,they were combined with a cyclic RGD peptide(cRGD).Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD,which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature.In this multifaceted approach,co-delivery of VEGF siRNA and phenethyl isothiocyanate(PEITC)was employed to target both tumor vascular endothelial cells and tumor cells simultaneously.The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF,inhibit the accumulation of HIF-1α under hypoxic conditions,and induce apoptosis in tumor cells.In summary,we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis,which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
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