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Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab

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Cancer Biology & Medicine 2020年第2期17卷 433-443页

作者： Chao Yang Yanli Tan Hongzhao Qi Junhu Zhou Lixia Long Qi Zhan Yunfei Wang Xubo Yuan Chunsheng Kang Department of Neurosurgery Tianjin Medical University General HospitalTianjin 300052China Tianjin Neurological Institute Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjin 300052China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 071000China Department of Pathology Hebei University Medical CollegeBaoding 071000China Tianjin Key Laboratory of Composite and Functional Materials School of Material Science and EngineeringTianjin UniversityTianjin 300072China institute for Translational Medicine Qingdao UniversityQingdao 266021China Affiliated Cancer Hospital 8l Institute of Guangzhou Medical University Guangzhou 510095China

Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.Methods:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(epr)effect.This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system.The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.Results:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native cetuximab.Nano(cetuximab)accumulated in tumor tissues via the epr effect and released cetuximab.The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the epr effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 weeks.Conclusions:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the epr effect,which facilitated further tumor accumulation of the tAbs.This novel self-augmentation of the epr effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.

关键词： Endothelial cells epr effect nanocapsule single dose administration therapeutic antibody

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Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

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Frontiers of Medicine 2018年第6期12卷 667-677页

作者： Yinlong Zhang Guangna Liu Jingyan Wei Guangjun Nie College of Pharmaceutical Science Jilin UniversityChangchun 130021China CAS Key Laboratory for Biomedical effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.

关键词： platelet-mimicking delivery systems tumor-associated platelets cancer therapy epr effect

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Traceable Drug Release Through a Drug Delivery System with Aggregation-Induced Emission

Traceable Drug Release Through a Drug Delivery System with A...

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第八届全国化学生物学学术会议

作者： Xiangdong Xue Chunqiu Zhang Guozhang Zou Xiejing Liang CAS Key Laboratory for Biological effects of Nanomaterials ＆ Nanosafety National Center for Nanoscience and Technology

＜正＞In the past decades,chemotherapeutics are the primary treatment options applicable to cancers.However,most anti-cancer drugs have poor water solubility,rapid blood clearance and severe side effects for normal tissues.In an attempt to overcome these drawbacks,various nanoscaled drug delivery systems（DDSs）such as,dendrimers,vesicles,liposomes,micelles

关键词： DDS epr effect AIE self-localization

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Developing polymeric micelles for cancer targeted theranostics

Developing polymeric micelles for cancer targeted theranosti...

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中国化学会2017全国高分子学术论文报告会

作者：米鹏四川大学生物治疗国家重点实验室

Polymeric micelles are generally constructed with a protecting shell of a hydrophilic polymer for shelling the hydrophobic core, demonstrating high performance for cancer therapy. Herein, we have developed several kinds of polymeric micelles for cancer imaging, imaging-guided therapy and tumor-targeted therapy, by incorporating with different kinds of imaging probes and bioactive compounds, demonstrating high performances in cancer theranostics.

关键词： Polymeric micelles tumor drug delivery system epr effect therapy

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