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Engineering platelet-mimicking drug delivery vehicles

Quanyin Hu, Hunter N. Bomba, Zhen Gu

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 624-632 doi: 10.1007/s11705-017-1614-6

摘要： Platelets dynamically participate in various physiological processes, including wound repair, bacterial clearance, immune response, and tumor metastasis. Recreating the specific biological features of platelets by mimicking the structure of the platelet or translocating the platelet membrane to synthetic particles holds great promise in disease treatment. This review highlights recent advancements made in the platelet-mimicking strategies. The future opportunities and translational challenges are also discussed.

关键词： drug delivery     platelets     nanomedicine     bio-inspired     biomimetic    

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

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

《医学前沿（英文）》 2018年 第12卷 第6期   页码 667-677 doi: 10.1007/s11684-017-0583-y

摘要： 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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Controlled drug delivery systems: the next 30 years

Yeonhee YUN,Byung Kook LEE,Kinam PARK

《化学科学与工程前沿（英文）》 2014年 第8卷 第3期   页码 276-279 doi: 10.1007/s11705-014-1426-x

摘要： The drug delivery scientists need to reexamine the advances made during the past 60 years, analyze our current abilities, and design the future technologies that will propel us to achieve the next level of drug delivery technologies. History shows that the first generation (1G) of drug delivery research during 1950–1980 was quite productive, while the second generation (2G) technologies developed during 1980–2010 were not as prolific. The ultimate goal of drug delivery research is to develop clinically useful formulations to treat various diseases. Effective drug delivery systems can be developed by overcoming formulation barriers and/or biological barriers. The engineering approach has a limit in solving the problem, if biological difficulties are not clearly identified and understood. The third generation (3G) drug delivery systems will have to focus on understanding the biological barriers so that they can be overcome by engineering manipulation of the drug delivery systems. Advances in the next 30 years will be most accelerated by starting open dialogues without any preconceived ideas on drug delivery technologies. The new generation of drug delivery scientists needs to be aware of the successes and limitations of the existing technologies to design the new technologies for meaningful advances in the future.

关键词： drug delivery     history     formulation barriers     nanotechnology     clinical product    

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Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

《化学科学与工程前沿（英文）》 2023年 第17卷 第2期   页码 123-138 doi: 10.1007/s11705-022-2194-7

摘要： The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many tissues. NAD(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most cancers. Therefore, it could be a target for cancer therapy. Because it is a quinone reductase, many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose tumours. Its expression is higher in tumours than in normal tissues, and using target drugs such as β-lapachone to reduce side effects in normal tissues can help. However, the physicochemical properties of β-lapachone limit its application. The problem can be solved by using nanosystems to deliver β-lapachone. This mini-review summarizes quinone-based fluorescent, near-infrared and two-photon fluorescent probes, as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drug β-lapachone. This review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

关键词： NAD(P)H:quinone oxidoreductase 1     cancer therapy     target     probe     nanosystem    

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Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 496-507 doi: 10.1007/s11705-013-1362-1

摘要： Successful development of a new drug is prohibitively expensive, and is estimated to cost approximately $100–500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attributes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appropriately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10 –10 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future “drug-of-choice”. Yet, among the>10000 drugs that are currently available, only ~150 of them belong to these bio-macromolecular drugs (an exceedingly low 1.2%), reflecting the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio-macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collectively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.

关键词： delivery systems     bio-macromolecular drugs     cell penetrating peptides    

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Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis

《医学前沿（英文）》 2022年 第16卷 第3期   页码 416-428 doi: 10.1007/s11684-021-0838-5

摘要： Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton’s tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

关键词： abivertinib     Btk inhibitor     platelet     megakaryocyte     megakaryopoiesis     thrombopoiesis    

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Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 139-152 doi: 10.1007/s11684-017-0551-6

摘要：

Current research on common musculoskeletal problems, including osteoarticular conditions, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients’ outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rich plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.

关键词： regenerative medicine     joint conditions     muscle injuries     platelet rich plasma     tendinopathy     healing mechanisms    

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The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 447-451 doi: 10.1007/s11684-009-0082-x

摘要： This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and- D were all higher in the experimental group than in the control group (<0.05); no significant difference was found in the expression of PDGF-C between the experimental group and the control group (>0.05). PDGF-A and -B expression was positively related with BVD and LVD (<0.01, R= 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.

关键词： cervical cancer     lymphatic vessel density     blood vessel density     platelet-derived growth factor    

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Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via two

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 76-84 doi: 10.1007/s11684-015-0426-7

摘要：

Anti-β2 glycoprotein I (anti-β2GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β2GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β2GP I antibodies in complexes with β2GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β2GP I /β2GP I complex. The interaction between the anti-β2GP I /β2GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B2 production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β2GP I /β2GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β2GP I /β2GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

关键词： anti-β2GP I /β2GP I complex     platelet     GP I bα     apoER2'     thrombosis    

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Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 116-122 doi: 10.1007/s11705-013-1310-0

摘要： Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy- -PMA). Various grades of Psy- -PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy- -PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy- -PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.

关键词： psyllium     acetyl salicylic acid     in-vitro drug release     swelling     biodegradation    

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Gene delivery into isolated

Nan Zheng, Ziyuan Song, Yang Liu, Lichen Yin, Jianjun Cheng

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 521-528 doi: 10.1007/s11705-017-1612-8

摘要： The application of gene delivery materials has been mainly focused on mammalian cells while rarely extended to plant engineering. Cationic polymers and lipids have been widely utilized to efficiently deliver DNA and siRNA into mammalian cells. However, their application in plant cells is limited due to the different membrane structures and the presence of plant cell walls. In this study, we developed the cationic, -helical polypeptide that can effectively deliver DNA into both isolated protoplasts and intact leaves. The PPABLG was able to condense DNA to form nanocomplexes, and they exhibited significantly improved transfection efficiencies compared with commercial transfection reagent Lipofectamine 2000 and classical cell penetrating peptides such as poly(L-lysine), HIV-TAT, arginine9, and poly(L-arginine). This study therefore widens the utilities of helical polypeptide as a unique category of gene delivery materials, and may find their promising applications toward plant gene delivery.

关键词： α-helical polypeptide     plant gene delivery     protoplast     intact leaves     transfection    

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Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug DeliverySystems

Zhijian CHEN, Wei LI,

《化学科学与工程前沿（英文）》 2010年 第4卷 第1期   页码 1-1 doi: 10.1007/s11705-009-0306-2

摘要：
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Bioorthogonal chemistry based on-demand drug delivery system in cancer therapy

《化学科学与工程前沿（英文）》 2023年 第17卷 第4期   页码 483-489 doi: 10.1007/s11705-022-2227-2

摘要： Benefiting from the advantage of taking place in biological environments without interfering with an innate biochemical process, the bioorthogonal reaction that commonly contains the “bond formation” and “bond cleavage” system has been widely used in targeted therapy for a variety of tumors. Herein, several prominent cases based on the bioorthogonal reaction that tailoring the metabolic glycoengineering tactics to modified cells for cancer immunotherapy, and the innovative tactics for reducing the metal ions’ toxic and side effects with microneedle patches will be highlighted. Based on these applications, the complexities, potential pitfalls, and opportunities of bioorthogonal chemistry in future cancer therapy will be evaluated.

关键词： bioorthogonal reaction     cancer therapy     metabolic glycoengineering     bioorthogonal catalytic patch    

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Effect of the new maternity insurance scheme on medical expenditures for caesarean delivery in Wuxi,

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 473-480 doi: 10.1007/s11684-016-0479-

摘要：

Aiming to control rising medical expenditures and help improve China’s healthcare systems, this study examined whether a cap-based medical insurance scheme with shared financial interest between the insurance and healthcare providers is effective in containing hospitals’ C-section medical expenditures. We used 6547 caesarean delivery case records from a teaching tertiary-level general public hospital located in Wuxi, China (2004–2013), and used the Chow test to investigate the possibility of significant variation in mean medical expenditures for caesarean deliveries pre- and post-reform. We also used paired sample t-tests and linear regression models to compare the mean medical expenditures between insured and uninsured women undergoing caesarean delivery during the post-reform period. After the scheme’s implementation, medical expenditures for caesarean deliveries declined and the medical expenditures of women covered by the scheme were significantly lower than those of uninsured patients. These findings indicated the scheme’s effectiveness in minimizing caesarean delivery expenditures. The cap-based medical insurance scheme with shared financial interest between insurance and healthcare providers would likely steer healthcare providers’ behaviors in a more cost-effective direction.

关键词： maternity insurance scheme     financial incentive     caesarean delivery     medical expenditure     China    

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polycarbonateurethane surface with poly(ethylene glycol) monoacrylate and phosphorylcholine glyceraldehyde for anti-platelet

Jing YANG,Juan LV,Bin GAO,Li ZHANG,Dazhi YANG,Changcan SHI,Jintang GUO,Wenzhong LI,Yakai FENG

《化学科学与工程前沿（英文）》 2014年 第8卷 第2期   页码 188-196 doi: 10.1007/s11705-014-1414-1

摘要： Poly(ethylene glycol) monoacrylate (PEGMA) is grafted onto polycarbonateurethane (PCU) surface via ultraviolet initiated photopolymerization. The hydroxyl groups of poly(PEGMA) on the surface react with one NCO group of isophorone diisocyanate (IPDI) and another NCO group of IPDI is then hydrolyzed to form amino terminal group, which is further grafted with phosphorylcholine glyceraldehyde to establish a biocompatible hydrophilic structure on the surface. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirm the successful grafting of both PEG and phosphorylcholine functional groups on the surface. The decrease of the water contact angle for the modified film is caused by synergic effect of PEG and phosphorylcholine, which both have the high hydrophilicity. Furthermore, the number of platelets adhered is relative low on the synergetically modified PCU film compared with the PCU film modified only by poly(PEGMA). Our synergic modification method using both PEG and phosphorylcholine may be applied in surface modification of blood-contacting biomaterials and some relevant devices.

关键词： poly(ethylene glycol) monoacrylate     phosphorylcholine     polycarbonateurethane     surface modification     anti-platelet adhesion     biomaterials    

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标题 作者 时间 类型 操作

Engineering platelet-mimicking drug delivery vehicles

Quanyin Hu, Hunter N. Bomba, Zhen Gu

期刊论文

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

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

期刊论文

Controlled drug delivery systems: the next 30 years

Yeonhee YUN,Byung Kook LEE,Kinam PARK

期刊论文

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

期刊论文

Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

期刊论文

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis

期刊论文

Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions

null

期刊论文

The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

期刊论文

Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via two

null

期刊论文

Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

期刊论文

Gene delivery into isolated

Nan Zheng, Ziyuan Song, Yang Liu, Lichen Yin, Jianjun Cheng

期刊论文

Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug DeliverySystems

Zhijian CHEN, Wei LI,

期刊论文

Bioorthogonal chemistry based on-demand drug delivery system in cancer therapy

期刊论文

Effect of the new maternity insurance scheme on medical expenditures for caesarean delivery in Wuxi,

null

期刊论文

polycarbonateurethane surface with poly(ethylene glycol) monoacrylate and phosphorylcholine glyceraldehyde for anti-platelet

Jing YANG,Juan LV,Bin GAO,Li ZHANG,Dazhi YANG,Changcan SHI,Jintang GUO,Wenzhong LI,Yakai FENG

期刊论文