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Featured researches published by Haihua Xiao.


Biomaterials | 2011

Biodegradable polymer - cisplatin(IV) conjugate as a pro-drug of cisplatin(II)

Haihua Xiao; Ruogu Qi; Shi Liu; Xiuli Hu; Taicheng Duan; Yonghui Zheng; Yubin Huang; Xiabin Jing

A Pt(IV) complex was covalently conjugated to a new biodegradable amphiphilic tri-block copolymer, MPEG-b-PCL-b-PLL, which contains pendant amino groups, to form a polymeric pro-drug of cisplatin(II), MPEG-b-PCL-b-PLL/Pt(IV). The conjugate was assembled into nano-micelles. The Pt(IV) complex, the polymer carrier and the conjugate were characterized systematically. In vitro release experiments showed that drug release from the polymer-Pt(IV) micelles follows an acid responsive and oxidation-reduction sensitive kinetics. HPLC-ICP-MS analysis revealed that cisplatin(II) can be released from the conjugate under an acidic plus a reductive condition which is available inside a cancerous cell. In vitro MTT assay demonstrated that the polymer-Pt(IV) micelles display higher cytotoxicity against SKOV-3 tumor cells than both cisplatin(II) and Pt(IV) complex. This enhanced cytotoxicity is attributed to effective internalization of the micelles by the cells via endocytosis mechanism, which was observed by fluorescence imaging and by direct determination of the platinum uptake by the cells. This polymer-Pt(IV) conjugate is a promising polymeric pro-drug of cisplatin in micellar form. It can protect the Pt(IV) complex against blood clearance. It can enter cancerous cells via endocytosis mechanism and then cisplatin(II) can be released. Therefore, this polymeric pro-drug of cisplatin is expected to find clinical applications in the future.


Biomaterials | 2012

A prodrug strategy to deliver cisplatin(IV) and paclitaxel in nanomicelles to improve efficacy and tolerance

Haihua Xiao; Haiqin Song; Qiang Yang; Haidong Cai; Ruogu Qi; Lesan Yan; Shi Liu; Yonghui Zheng; Yubin Huang; Tongjun Liu; Xiabin Jing

A strategy of preparing composite micelles containing both cisplatin(IV) prodrug and paclitaxel was developed, i.e., synthesizing a cisplatin(IV) conjugate and a paclitaxel conjugate starting with the same biodegradable and amphiphilic block copolymer, and co-assembling the two conjugates. The composite micelles could release effective anticancer drug cisplatin(II) upon cellular reduction and PTX via acid hydrolysis once they came into the cancerous cells. Moreover, the composite micelles displayed synergistic effect in vitro and the combination therapy in micellar dosage-form led to reduced systematic toxicity and enhanced antitumor efficacy in vivo.


Journal of Controlled Release | 2012

Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy

Haihua Xiao; Wenliang Li; Ruogu Qi; Lesan Yan; Rui Wang; Shi Liu; Yonghui Zheng; Zhigang Xie; Yubin Huang; Xiabin Jing

An oxaliplatin pro-drug (Oxa(IV)-COOH) with an axial carboxyl group was synthesized and conjugated to biodegradable polymers with pendant hydroxyl groups to prepare polymer-Oxa(IV) conjugates. A hydrophobic anthracycline-based drug, daunorubicin (DRB) was conjugated to similar biodegradable polymers with carboxyl groups to synthesize polymer-DRB conjugates. The two drug conjugates have the similar polymer backbone and are amphiphilic; thus, they can co-assemble into composite micelles. In the composite micelles, the polymer-Oxa(IV) conjugates can release clinically widely used water soluble anticancer drug oxaliplatin (Oxa(II)) upon reduction, while polymer-DRB conjugate is thought to release DRB via acid hydrolysis in the cancer cells. In this way, combination of the hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB can be realized by delivering them in one platform. Moreover, the composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of the two anticancer drugs both in vitro and in vivo; thus, this polymer based combination therapy can be useful in future clinic application.


Biomaterials | 2012

The use of polymeric platinum(IV) prodrugs to deliver multinuclear platinum(II) drugs with reduced systemic toxicity and enhanced antitumor efficacy

Haihua Xiao; Haiqin Song; Yu Zhang; Ruogu Qi; Rui Wang; Zhigang Xie; Yubin Huang; Yuxin Li; Yin Wu; Xiabin Jing

Two dinuclear platinum(IV) prodrugs were prepared from cisplatin and oxaliplatin, and tethered to amphiphilic biodegradable block copolymers. The polymeric dinuclear platinum(IV) prodrugs were allowed to self-assemble into nanomicelles, which showed reduced systemic toxicity, relatively long blood circulation, and enhanced antitumor efficacy. In this way, the bottleneck of present multinuclear platinum drugs, especially their severe systemic toxicity, might be overcome.


Colloids and Surfaces B: Biointerfaces | 2014

Synthesis of mesoporous silica nanoparticle–oxaliplatin conjugates for improved anticancer drug delivery

Hongyan He; Haihua Xiao; Huihui Kuang; Zhigang Xie; Xuesi Chen; Xiabin Jing; Yubin Huang

Mesoporous silica nanoparticles (MSN) with 1,2-bidentate carboxyl groups on the surface reacted with 1,2-diaminecyclohexano platinum(II) dinitrate (DACH-Pt-(NO3)2) which is an active anticancer species of clinic relevant oxaliplatin to form MSN-Pt. The modification of the parent particles was monitored by (13)C, (29)Si solid-state NMR, X-ray measurements (XRD) and Fourier transform infrared spectroscopy (FT-IR). After loading with platinum drugs, MSN-Pt exhibited two strong Pt4f signals as indicated by X-ray photoelectron spectroscopy (XPS). The platinum content in the conjugates was calculated to be 9.7% according to ICP-MS measurements. Confocal laser scanning microscopy (CLSM) displayed that MSN-Pt were uptaken fast by HepG-2 cells and concentrated within endosomes and lysosomes. In vitro MTT assay of MSN-Pt demonstrated an improved cytotoxicity against HepG-2 cells than that of free oxaliplatin. This is due to the fact that MSN-Pt expressed higher platinum intracellular uptake and more DNA binding (Pt-DNA adducts) than free oxaliplatin. Hence this work highlighted that the platinum loaded MSN nanoparticles could be a promising future intelligent drug delivery system.


Nano Letters | 2017

Enhanced Cisplatin Chemotherapy by Iron Oxide Nanocarrier-Mediated Generation of Highly Toxic Reactive Oxygen Species

Ping’an Ma; Haihua Xiao; Chang Yu; Jianhua Liu; Ziyong Cheng; Haiqin Song; Xinyang Zhang; Chunxia Li; Jinqiang Wang; Zhen Gu; Jun Lin

Reactive oxygen species (ROS) plays a key role in therapeutic effects as well as side effects of platinum drugs. Cisplatin mediates activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which triggers oxygen (O2) to superoxide radical (O2•-) and its downstream H2O2. Through the Fentons reaction, H2O2 could be catalyzed by Fe2+/Fe3+ to the toxic hydroxyl radicals (•OH), which cause oxidative damages to lipids, proteins, and DNA. By taking the full advantage of Fentons chemistry, we herein demonstrated tumor site-specific conversion of ROS generation induced by released cisplatin and Fe2+/Fe3+ from iron-oxide nanocarriers with cisplatin(IV) prodrugs for enhanced anticancer activity but minimized systemic toxicity.


Advanced Healthcare Materials | 2013

A Polymer-(Tandem Drugs) Conjugate for Enhanced Cancer Treatment

Dongfang Zhou; Haihua Xiao; Fanbo Meng; Xiaoyuan Li; Yuxin Li; Xiabin Jing; Yubin Huang

A novel strategy for combination chemotherapy (platinum and demethylcantharidin) via a polymer-(tandem drugs) conjugate for enhanced cancer treatment is demonstrated. Cisplatin can be released inside cell by reduction to attack DNA, while DMC will be hydrolyzed subsequently to block DNA-damage-induced defense mechanisms by serine/threonine phosphatase PP2A inhibition. Synergistic effect of the polymer-(tandem drugs) conjugate causes complete suppression of H22 liver tumor xenografts without recurrence.


Acta Biomaterialia | 2012

A complex of cyclohexane-1,2-diaminoplatinum with an amphiphilic biodegradable polymer with pendant carboxyl groups

Haihua Xiao; Dongfang Zhou; Shi Liu; Yonghui Zheng; Yubin Huang; Xiabin Jing

A biodegradable and amphiphilic copolymer, MPEG-b-P(LA-co-MCC), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (DACH-Pt) of oxaliplatin to form an MPEG-b-P(LA-co-MCC/Pt) complex. It was able to self-assemble into micelles with a mean diameter of 30-40 nm, and a surface potential near -10 mV. The typical platinum content was 10 wt.%. The micelles showed acid-responsive drug release kinetics, which is beneficial for drug release in the intracellular environment. The Pt(II) species were released mainly in the form of DACH-Pt-Cl(2) in 150 mM NaCl solution and DACH-Pt(2+)-(H(2)O)(2) in pure water according to the results obtained by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. In vitro evaluation showed that the micelles displayed the same or higher cytotoxicities against SKOV-3, HeLa, and EC-109 cancer cells compared with oxaliplatin. The enhanced cytotoxicity against SKOV-3 cells is attributed to effective internalization of the micelles by the cells via endocytosis and the sensitivity of SKOV-3 cells to platinum drugs. This novel biodegradable and amphiphilic copolymer-based platinum drug will have great potential application in clinical use.


Journal of Materials Chemistry B | 2013

Multifunctional Pt(IV) pro-drug and its micellar platform: to kill two birds with one stone

Haiqin Song; Haihua Xiao; Yu Zhang; Haidong Cai; Rui Wang; Yonghui Zheng; Yubin Huang; Yuxin Li; Zhigang Xie; Tongjun Liu; Xiabin Jing

A multifunctional hybrid platinum(iv) drug which has both DCA and Pt in one molecule was synthesized and tethered to polymers to further self-assemble into micelles. This micelle-mediated delivery of platinum(iv) prodrug aims to target both nuclear DNA and mitochondria.


RSC Advances | 2013

Iodo-BODIPY: a visible-light-driven, highly efficient and photostable metal-free organic photocatalyst

Wenliang Li; Leijiao Li; Haihua Xiao; Ruogu Qi; Yubin Huang; Zhigang Xie; Xiabin Jing; Hong-Xing Zhang

Boron-dipyrromethene (BODIPY) compounds have been used extensively. However, their application in photocatalysis has not been well-studied. In this report, iodo-BODIPYs were utilized as visible-light-driven photocatalysts. They demonstrated very high catalytic efficiencies and reaction rates for the photocatalyzed oxidation of thioanisole under visible light.

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Xiabin Jing

Chinese Academy of Sciences

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Yubin Huang

Chinese Academy of Sciences

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Ruogu Qi

Chinese Academy of Sciences

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Zhigang Xie

Chinese Academy of Sciences

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Lesan Yan

Chinese Academy of Sciences

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Rui Wang

Chinese Academy of Sciences

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Shi Liu

Chinese Academy of Sciences

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Dongfang Zhou

Chinese Academy of Sciences

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Wenliang Li

Northeast Normal University

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Xiuli Hu

Chinese Academy of Sciences

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