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Cancer nanomedicine in preoperative therapeutics:Nanotechnology-enabled neoadjuvant chemotherapy,radiotherapy,immunotherapy,and phototherapy

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Bioactive Materials 2023年第6期24卷 136-152页

作者： Xiaogang Qu Dong Zhou Jianpu Lu Duotian Qin Jun Zhou Hai-Jun Liu Department of General Surgery Changshu Hospital Affiliated to Nanjing University of Chinese MedicineChangshu215500China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115USA

Surgical resection remains a mainstay in the treatment of malignant solid tumors.However,the use of neoadjuvant treatments,including chemotherapy,radiotherapy,phototherapy,and immunotherapy,either alone or in combination,as a preoperative intervention regimen,have attracted increasing attention in the last decade.Early randomized,controlled trials in some tumor settings have not shown a significant difference between the survival rates in long-term neoadjuvant therapy and adjuvant therapy.However,this has not hampered the increasing use of neoadjuvant treatments in clinical practice,due to its evident downstaging of primary tumors to delineate the surgical margin,tailoring systemic therapy response as a clinical tool to optimize subsequent therapeutic regimens,and decreasing the need for surgery,with its potential for increased morbidity.The recent expansion of Nanotechnology-based nanomedicine and related medical technologies provides a new approach to address the current challenges of neoadjuvant therapy for preoperative therapeutics.This review not only summarizes how nanomedicine plays an important role in a range of neoadjuvant therapeutic modalities,but also highlights the potential use of nanomedicine as neoadjuvant therapy in preclinical and clinic settings for tumor management.

关键词： Neoadjuvant treatment Preoperative preparation Surgical resection Nanotechnology

Minimizing sperm oxidative stress using Nanotechnology for breeding programs in rams

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2395-2410页

作者： Alejandro Jurado‑Campos Pedro Javier Soria‑Meneses Maria Arenas‑Moreira Carlos Alonso‑Moreno Virginia Rodriguez‑Robledo Ana Josefa Soler Jose Julian Garde Maria del Rocio Fernandez‑Santos SaBio IREC(CSIC-UCLM-JCCM) Campus UniversitarioS/N02071 AlbaceteSpain. Departamento de Quimica Inorganica Organica Y Bioquimica‑Centro de Innovacion en Quimica Avanzada(ORFEO‑CINQA)Facultad de FarmaciaUniversidad de Castilla-La Mancha02008 AlbaceteSpain. Centro Regional de Investigacion Biomedicas Unidad nanoDrugUniversidad de Castilla-La Mancha02008 AlbaceteSpain. Facultad de Farmacia Universidad de Castilla La Mancha02071 AlbaceteSpain.

Background Artificial insemination(AI)is a routine breeding technology in animal reproduction.Nevertheless,the temperature-sensitive nature and short fertile lifespan of ram sperm samples hamper its use in AI.In this sense,Nanotechnology is an interesting tool to improve sperm protection due to the development of nanomaterials for AI,which could be used as delivery vehicles.In this work,we explored the feasibility of vitamin E nanoemulsion(NE)for improving sperm quality during transport.Results With the aim of evaluating this proposal,ejaculates of 7 mature rams of Manchega breed were collected by artificial vagina and extended to 60×10^(6)spz/mL in AndromedR.Samples containing control and NE(12 mmol/L)with and without exogenous oxidative stress(100μmol/L Fe2+/ascorbate)were stored at 22 and 15℃and motility(CASA),viability(YO-PRO/PI),acrosomal integrity(PNA-FITC/PI),mitochondrial membrane potential(Mitotracker Deep Red 633),lipoperoxidation(C11 BODIPY 581/591),intracellular reactive oxygen species(ROS)production and DNA status(SCSAR)monitored during 96 h.Our results show that NE could be used to maintain ram spermatozoa during transport at 15 and 22℃for up to 96 h,with no appreciable loss of kinematic and physiological characteristics of freshly collected samples.Conclusions The storage of ram spermatozoa in liquid form for 2-5 d with vitamin E nanoemulsions may lead more flexibility to breeders in AI programs.In view of the potential and high versatility of these nanodevices,further studies are being carried out to assess the proposed sperm preservation medium on fertility after artificial insemination.

关键词： Breeding technology Nanoemulsions Nanotechnology Sperm oxidative stress Vitamin E

Emerging vaccine Nanotechnology: From defense against infection to sniping cancer

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2206-2223页

作者： Chan Feng Yongjiang Li Bijan Emiliano Ferdows Dylan Neal Patel Jiang Ouyang Zhongmin Tang Na Kong Enguo Chen Wei Tao Department of Respiratory Medicine Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Cancer Center Zhejiang UniversityHangzhou 310058China Department of Pharmacy the Second Xiangya Hospital of Central South UniversityChangsha 410011China

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019(COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of Nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation,antigen assembly, and antigen presentation;they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine Nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal.In this review, we summarize the recent advances in vaccine Nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

关键词： Vaccine Nanotechnology Infection Cancer Nanovaccines Vaccination Diseases prevention Immunotherapy

Nanotechnology:A New Strategy for Lung Cancer Treatment Targeting Pro-Tumor Neutrophils

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Engineering 2023年第8期27卷 106-126页

作者： Jian Zhang Shasha Jiang Shilin Li Jipeng Jiang Jie Mei Yandong Chen Yongfu Ma Yang Liu Ying Liu Department of Thoracic Surgery The First Medical Center of the Chinese PLA General HospitalBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China Postgraduate School Medical School of the Chinese PLABeijing 100853China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijing 100190China University of Chinese Academy of Science Beijing 100049China The Great Bay Area National Institute for Nanotechnology Innovation Guangzhou 510700China

Primary and metastatic lung cancers are malignant lung tumors each with of which has a different pathogenesis,although both threaten patient lives.Tumor development and progression involve communication between tumor cells and the host microenvironment.Neutrophils are the most abundant immune cells in the tumor microenvironment(TME);they participate in the generation of an inflammatory milieu and influence patient survival through their anti-and pro-tumor abilities.Neutrophils can be classified into various categories according to different criteria;frequent categories include N1 antitumor neutrophils and N2 immunosuppressive neutrophils.The antitumor effects of neutrophils are reported to be mediated through a combination of reactive oxygen species,tumor necrosis factor-related apoptosis-inducing ligand,and receptor for advanced glycation end-products–cathepsin G association,as well as the regulation of the activities of other immune cells.There have also been reports that neutrophils can function as tumor promoters that contribute to lung cancer progression and metastasis by influencing processes including carcinogenesis,angiogenesis,cancer cell proliferation,and invasion ability,as well as having similar roles in the lung metastasis of other cancers.The rapid development of Nanotechnology has provided new strategies for cancer treatment targeting neutrophils.

关键词： Lung cancer Metastasis Neutrophils Tumor microenvironment Nanotechnology

Nanotechnology-based combinational strategies toward the regulation of myofibroblasts and diseased microenvironment in liver fibrosis and hepatic carcinoma

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Nano Research 2023年第12期16卷 13042-13055页

作者： Fenfen Li Ying Zhao Guangjun Nie School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 101408China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China GBA National Institute for Nanotechnology Innovation Guangzhou 510530China

Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic HCC.HSCs play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver fibrosis.CAFs can be derived from activated HSCs and differentiate into ECM-producing myofibroblasts.Moreover,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune response.Combined therapeutic strategies show reduced drug resistance and side effects.Nanotechnology-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple mechanisms.In this review,we will discuss recent developments in combinational strategies based on Nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC treatment.We will also identify the major challenges that the field is facing and offer some insights for future drug discovery.

关键词： fibroblasts liver fibrosis hepatic carcinoma Nanotechnology

Exosomes: Emerging implementation of Nanotechnology for detecting and managing novel corona virus-SARS-CoV-2

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 20-34页

作者： Akhilesh Dubey Cynthia Lizzie Lobo Ravi GS Amitha Shetty Srinivas Hebbar Sally AEl-Zahaby Department of Pharmaceutics NGSM Institute of Pharmaceutical SciencesNitte(Deemed to be University)Mangaluru 575018India Formulation and Development Viatris R&D CentreBengaluru 560105India Department of Pharmaceutics and Pharmaceutical Technology Faculty of PharmacyPharos University in AlexandriaAlexandria 21311Egypt

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to mediate intercellular communications. The exosomal cargo serves as biomarkers in diagnosing various diseases;moreover, exosomes could be employed as nanocarriers in drug delivery systems. Exosomes look promising to combat the current pandemic since they contribute to the immune response against several viral pathogens. Many studies have proved the potential of using exosomes either as viral elements or host systems that acquire immune-stimulatory effects and could be used as a vaccine or drug delivery tool. It is essential to stop viral replication, prevent and reverse the massive storm of cytokine that worsens the infected patients’ situations for the management of COVID-19. The main benefits of exosomes could be;no cells will be introduced, no chance of mutation, lack of immunogenicity and the damaged genetic material that could negatively affect the recipient is avoided. Additionally, it was found that exosomes are static with no ability for in vivo reproduction. The current review article discusses the possibilities of using exosomes for detecting novel coronavirus and summarizes state of the art concerning the clinical trials initiated for examining the use of COVID-19 specific T cells derived exosomes and mesenchymal stem cells derived exosomes in managing COVID-19.

关键词： Exosomes COVID-19 Specific T cell-derived exosomes Mesenchymal stem cells-derived exosomes Nanotechnology SARS-Co V-2

Application of Nanotechnology in CAR-T-cell immunotherapy

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Chinese Chemical Letters 2023年第3期34卷 49-65页

作者： Qiang Zeng Zhigang Liu Ting Niu Chuan He Ying Qu Zhiyong Qian Department of Hematology and Institute of Hematology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

It is cellular immunotherapy for the tumor that the in vitro modified immunocytes from patients or donors are reinfused into patients to kill tumor cells.Chimeric antigen receptor T cell(CAR-T)therapy,one of the most successful and representative tumor cellular immunotherapies,is now the weapon for cancer after extensive research.Although CAR-T immunotherapy achieves success in treating relapsed/refractory hematological tumors,its drawbacks,including the poor effect in solid tumors,cytokine release syndrome(CRS)or CAR-T-related encephalopathy syndrome(CRES),on-target,off-tumor effect,and high cost,cannot be overlooked.Nanotechnology is advantageous in the construction of CARs,the transfection of T cells,the expansion,delivery,and antitumor effect of CAR-T cells,and the reduction of CAR-T therapy-associated toxicities.Currently,introducing Nanotechnology into CAR-T immunotherapy has already been performed in numerous studies with highly promising results.In this review,we summarized the nanotechnologies used in CAR-T immunotherapy and discussed the challenges and directions of CAR-T immunotherapy combined with nanotechnologies in the future.

关键词： CAR-T immunotherapy Nanotechnology Nanobody Nanoparticle

Applying Nanotechnology to boost cancer immunotherapy by promoting immunogenic cell death

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Chinese Chemical Letters 2022年第4期33卷 1718-1728页

作者： Lvqin Fu Xianbin Ma Yuantong Liu Zhigang Xu Zhijun Sun The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhan 430079China Key Laboratory of Luminescence Analysis and Molecular Sensing Ministry of EducationSchool of Materials and Energy&Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and DevicesSouthwest UniversityChongqing 400715China

Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a death mode of tumor cells that can promote tumor immunity.ICD can induce strong an-titumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1(HMGB1),ATP,and in-terferon(IFN),thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy.Chemotherapy,radiotherapy,photothermal therapy,magneto-thermodynamics therapy,nanopulse stimulation,and oncolytic virus therapy can all induce a strong antitumor immune response by ICD.In addition,the application of Nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy.Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD.Then,we summarize and discuss the progress in the application of Nanotechnology in immunotherapy to promote ICD.Finally,we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.

关键词： Immunogenic cell death Nanotechnology Cancer immunotherapy Combination therapy Immune checkpoint blockade

Recent progress of Nanotechnology-based theranostic systems in cancer treatments

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Cancer Biology & Medicine 2021年第2期18卷 336-351页

作者： Ying Xue Yuting Gao Fanling Meng Liang Luo National Engineering Research Center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica School of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074China Research Institute of Huazhong University of Science and Technology in Shenzhen Shenzhen 518057China

Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy.Nanoparticles are ideal candidates as carriers for theranostic agents,which is attributed to their extraordinary physicochemical properties,including nanoscale sizes,functional properties,prolonged blood circulation,active or passive tumor targeting,specific cellular uptake,and in some cases,excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time.Overall,with the development of Nanotechnology,theranostics has become a reality,and is now in the transition stage of"bench to bedside."In this review,we summarize recent progress on Nanotechnology-based theranostics,i.e.,nanotheranostics,that has greatly assisted traditional therapies,and has provided therapeutic strategies emerging in recent decades,as well as"cocktail"theranostics mixing various treatment modalities.

关键词： Theranostics cancer therapy diagnosis nanoparticles Nanotechnology