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Phenylboronic acid-modified hollow silica nanoparticles for dual-responsive delivery of doxorubicin for targeted tumor therapy

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Regenerative Biomaterials 2017年第2期4卷 111-124页

作者： Ling Huang Qingfeng Zhang Liangliang Dai Xinkun Shen Weizhen Chen Kaiyong Cai Key Laboratory of Biorheological Science and Technology Ministry of Education College of BioengineeringChongqing UniversityChongqing 400044P.R.China

This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles(HMSNs)for targeting tumor therapy.Doxorubicin(DOX)was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid(CytC–LA)via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers.The CytC–LA was used both as sealing agent and targeting motif.A series of characterizations demonstrated the successful construction of the drug delivery system.The system demonstrated pH and redox dual-responsive drug release behavior in vitro.The DOX loading HMSNs system displayed a good biocompatibility,which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis.In vivo data(tumor volume,tumor weight,terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining)proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect.

关键词： hollow mesoporous silica nanoparticles dual-response drug delivery targeted tumor therapy in vivo

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The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1761-1780页

作者： Tiecheng Zhong Wenxin Zhang Hongjie Guo Xiaohui Pan Xi Chen Qiaojun He Bo Yang Ling Ding Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China

Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.

关键词： TRP channels Cancer progression tumor microenvironment tumor-associated immunocytes Intracellular mechanism Programmed cancer cell death targeted tumor therapy

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Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy

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药物分析学报:英文版 2023年第7期13卷 776-787页

作者： Xiangyi Wang Jin Zhang Kailu Zheng Qianqian Du Guocai Wang Jianpeng Huang Yanhe Zhou Yan Li Hongtao Jin Jiuming He State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China NMPA Key Laboratory of Safety Research and Evaluation of Innovative Drug Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China New Drug Safety Evaluation Center Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.

关键词： Mass spectrometry imaging Spatially resolved metabolomics Small molecule-drug conjugate tumor metabolism targeted tumor therapy

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Selected Secondary Plant Metabolites for Cancer therapy

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World Journal of Traditional Chinese Medicine 2015年第1期1卷 24-28页

作者： Simone Fulda Thomas Efferth Institute of Experimental Cancer Research in Pediatry Goethe-Universitat Frankfurt Department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg-Universitat Mainz

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases.As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics,either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology.Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid,artesunate, dicentrine and camptothecin derivatives.

关键词： Apoptosis Bioactivity-guided fractionation Drug development Drug resistance Epidermal growth factor receptor Phytochemicals targeted tumor therapy

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