JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Jinghao Wang,Wenmin Lin,Yuancai Chen,Yongyou Hu,Qijin Luo
Due to the excellent hydrogen affinity and high conductivity, palladium nanoparticles (Pd NPs) were considered as a potential strategy to regulate bacterial electron transfer and energy metabolism. Herein, Citrobacter freundii JH, capable of in-situ biosynthesizing Pd(0) NPs, was employed to promote Pt(IV) reduction. The results showed that the Pt(IV) reduction to Pt(II) was accomplished mainly via the flavins-mediated extracellular electron transfer (EET) process, while Pt(II) reduction to Pt(0) was limit step, and proceeded via two intracellular respiratory chains, including FDH/Hases-based short chain (S-chain) and typical CoQ-involved long respiratory chain ( L -chain). Noteworthily, the incorporation of Pd(0) NPs mainly diverted the electrons to S-chain (as high as 71.7%−73.4%) by improving the hydrogenases (Hases) activity. Furthermore, Pd(0) NPs could stimulate the secreting of flavins and the combination between flavins and cytochrome c (c-Cyt), which converted electron transfer manner of L -chain. Additionally, Pd(0) NPs might also act as alternative proton channels to improve the energy metabolism. These findings provided significant insights into the promotion by Pd(0) NPs in terms of electron generation, electron consumption and proton translocation.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
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IF 5.268
Xiao Kuang,Dongxu Chi,Jinbo Li,Chunlin Guo,Yinxian Yang,Shuang Zhou,Cong Luo,Hongzhuo Liu,Zhonggui He,Yongjun Wang
The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.
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Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 48
·9546-9557
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IF 4.543
Shao-Lu Li,Yaoyi Wang,Jingfang Zhang,Wei Wei,Hua Lu
We describe here a novel targeting polyion complex (Tg-PIC) system for the delivery and intracellular release of cisplatin. Briefly, a guanidinium-pendant Pt(IV)-backboned poly-prodrug termed P(DSP-Gu) is prepared with excellent aqueous solubility, high drug-loading and high potency. To enable prolonged circulation and selective cellular internalization, P(DSP-Gu) is complexed with anisamide-end-capped poly(ethylene glycol)-block-poly(L-phosphotyrosine)-block-poly(L-leucine) (AA-PEG-PpY-PLeu) to yield Tg-PIC via electrostatic coacervation. Tg-PIC is stabilized by hydrogen bonding between phosphate and guanidinium, the PEG corona, and the helical poly(L-leucine) segment forming the hydrophobic core. The anisamide group, a high affinity ligand recognizing the sigma (σ) receptors that are overexpressed on many human malignancies including prostate cancer, is incorporated at the surface of the Tg-PIC for active targeting and efficient internalization. In vitro, the Tg-PICs show targeted and efficient internalization into sigma receptor-positive PC3 cells, and can release toxic Pt(II) species due to the degradation of P(DSP-Gu) under the intracellular reducing conditions. In vivo, the Tg-PICs exhibit superior antitumor efficacy with reduced toxicity. Thus, the system holds considerable promise towards more effective and safe nanomedicine.
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Polymer Chemistry
·
2017
·Vol. 8
·期 15
·2410-2422
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IF 5.375
Zihao Zhang,Yongjing Li,Jiaxun Wan,Peihua Long,Jia Guo,Guosong Chen,Changchun Wang
Cisplatin is a widely-used chemotherapeutic drug in the clinic against a range of cancers. However, its anti-cancer efficacy and bioavailability are severely affected by systemic toxicity as well as drug resistance, which are mainly due to indiscriminate body distribution, low tumor accumulation and glutathione (GSH)-related drug detoxification. In this study, we prepared for the first time a new kind of Pt(IV)-crosslinked polymer nanoparticle with small, uniform size and high loading of cisplatin (60.8%). Such a kind of polymer nanodrug could keep its structural integrity during blood circulation to afford higher tumor accumulation via the EPR effect and receptor-mediated targeting effect, yet rapidly self-disintegrate to release drugs in response to tumor intracellular bio-reducing molecules, such as glutathione (GSH), resulting in efficient cancer cell inhibition and reduced systemic toxicity in vivo. Meanwhile, some of the cellular GSH molecules are depleted and transformed into an oxidized GSSG form to decrease their chelating interaction with platinum drugs, which attenuate their detoxifying effect on the Pt(II) species and may have an advantage for overcoming the tumor resistance to cisplatin induced by GSH. Moreover, the maximum tolerated dose of drug could be greatly enhanced (>3 fold), which improved the bioavailability of the nanodrug at relatively high doses. The present work provides a novel drug self-crosslinked design tactic and might open a new window for clinical cancer treatment.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Liu Wen,Jia Bin,Yang Feiya,Yin Lu,Tian Ziru,Sheng Guoli,Wang Wenkuan,Gao Yunhao,Zhang Lingpu,Wei Wenqiang,Xiao Haihua,Xing Nianzeng
Intravesical therapy is widely used in the management of bladder cancer. Nevertheless, continuous urinary flow accelerates the elimination of intravesically administered drugs, thereby reducing bladder residence time and therapeutic efficacy. Agents targeting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway have shown promising antitumor activity, yet their clinical translation is hindered by low local bioavailability and insufficient tumor selectivity. Here, a glutathione (GSH)-responsive nanoplatform, NP MP @Pt-MSA, was developed to integrate mucoadhesion with charge-mediated tissue penetration, thereby prolonging bladder retention and enhancing transurothelial delivery during intravesical administration. Upon cellular internalization, NP MP @Pt-MSA releases a Pt(IV) prodrug and the STING agonist MSA. DNA damage induced by the Pt(IV) prodrug promotes cytosolic dsDNA accumulation and activates the cGAS-STING pathway, while MSA further amplifies STING signaling, resulting in enhanced chemo-immunotherapeutic effects. In vivo, intravesical administration of NP MP @Pt-MSA significantly inhibited tumor growth, enhanced antitumor immune responses, and remodeled the immunosuppressive tumor microenvironment. Collectively, these findings establish a multifunctional intravesical delivery strategy that integrates mucoadhesive and tissue-penetrating nanoparticle design with dual chemo-immunomodulation, offering a promising approach to improve local therapy for bladder cancer. Graphical abstract
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Journal of Materials Chemistry B
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2020
·Vol. 8
·期 27
·5903-5911
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IF 5.344
Qingfei Zhang,Gaizhen Kuang,Dongfang Zhou,Yanxin Qi,Mingzhe Wang,Xiaoyuan Li,Yubin Huang
Endo/lysosomal escape and the subsequent controllable/precise release of drugs and genes are key challenges for efficient synergistic cancer therapy. Herein, we report a photoactivated polyprodrug nanoparticle system (PPNPsiRNA) centered on effective light-controlled codelivery of Pt(IV) prodrug and siRNA for synergistic cancer therapy. Under green-light irradiation, PPNPsiRNA can sustainedly generate oxygen-independent azidyl radicals to facilitate endo/lysosomal escape through the photochemical internalization (PCI) mechanism. Besides, concurrent Pt(II) release and siRNA unpacking could occur in a controllable manner after the decomposition of Pt(IV), main chain shattering of photoactivated polyprodrug and the PPNPsiRNA disassociation. Based on these innovative features, excellent synergistic therapeutic efficacy of chemo- and RNAi therapies of PPNPsiBcl-2 could be achieved on ovarian cancer cells under light irradiation. The facile synthesized and prepared photoactivatable polyprodrug nanoparticle system provides a new strategy for effective gene/drug codelivery, where controllable endo/lysosomal escape and the subsequent drug/gene release/unpacking play vital roles, which could be adopted as a versatile codelivery nanoplatform for the treatment of various cancers.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-20
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IF 12.6
Fang Man,Cao Lei,Zhang Zhao,Yu Zhen,Shen Yue,Chen Jieqi,Chen Juan,Li Yue-Qin,Liu Zhaoqian,Meng Yingcai,Xiao Haihua,Qu Qiang,Yin Ji-Ye,Li Xiang-Ping
Non-small cell lung cancer (NSCLC) represents the most prevalent form of lung cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is the standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted significant interest. While numerous studies concentrate on their functional modifications and targeted delivery, tumor-induced platinum resistance is frequently overlooked. Previous tetravalent platinum compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting resistance to cisplatin. In order to enhance the efficacy and potential applications of tetravalent platinum in NSCLC, a glutathione (GSH)-responsive albumin nanoquadrivalent platinum (HSA@Pt) have been constructed. In light of previous research into drug conjugation, this study was to develop a combined chemo-immunotherapy approach. The HSA@Pt demonstrated high efficacy and low toxicity, with targeted tumor accumulation. Furthermore, Ammonium Tetrathiomolybdate (TM) has been demonstrated to exert a synergistic inhibitory effect on ATPase Copper Transporting Beta (ATP7B) and Programmed Death Ligand 1 (PD-L1), impede platinum efflux, induce cellular stress, and activate antitumor immunity. The findings suggest HSA@Pt’s potential for clinical use and a novel chemo-immunotherapy strategy for NSCLC, enhancing the utility of established drugs through synergistic sensitization.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Lin An,Yuxi Jia,Jinran Li,Chunsheng Xiao
Melanoma, the deadliest skin cancer with high metastasis potential, has posed a great threat to human health. Accordingly, early efficient blocking of melanoma progression is vital in antitumor treatment. Herein, a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) was synthesized and used for doxorubicin (DOX) delivery to combat melanoma synergistically. First, PDPN was prepared by one-pot chemical coupling of carboxylated methoxy poly(ethylene glycol) (mPEG), dextran (Dex), and the crosslinking agent cisPt (IV)-COOH. PDPN had a spherical structure ( R h = 34 ± 11.3 nm). Then, DOX was encapsulated into the PDPN core to form DOX-loaded PDPN (PDPN-DOX). The obtained PDPN-DOX displayed reduction-responsive release of DOX and Pt, thus showing a synergistic anticancer effect in B16F10 cells (combination index, 0.46). Furthermore, in vivo experiments demonstrated that PDPN-DOX was effective for the synergistic treatment of subcutaneous melanoma. Collectively, the as-prepared PDPN could serve as a promising and versatile nano-prodrug carrier for the co-delivery of chemotherapeutics in tumor combination therapy.
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Analytical Methods
·
2022
·Vol. 14
·期 25
·2541-2548
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IF 3.532
Lixia Su,Yonghuan Su,Bingqian Liu
A new ratiometric electrochemical strategy for immobilization-free detection of Escherichia coli (E. coli) was constructed by using a capture DNA-polyaniline/copper ferrite nanoparticles/graphene oxide (cDNA-PANI/CuFe2O4/GO) composite as capture probes, which has a high specific surface area and good magnetic properties. Then trigger DNA/Au nanoparticles (tDNA/Au NPs) were used as signal amplification labels, and Pt (IV) and Fe (III) were chosen as the signal probes. In the presence of targets, the sandwich format among cDNA-PANI/CuFe2O4/GO, E. coli and auxiliary DNA (aDNA) was realized by using the aptamer recognition system. Then, the tDNA/Au binding could be anchored on the sandwich format due to the principle of base complementation between unpaired aDNA and tDNA. And the unbounded tDNA of tDNA/Au NPs could bind an amount of Pt (IV). After separation using a magnet, a handful of unbound Pt (IV) which remained in the supernatant reacted with a large number of Fe (III) ions, leading to a markedly increased IFe(III)/IPt(IV) value. Oppositely, the sandwich format could not appear in the absence of targets, and even the tDNA/Au could not be immobilized on it. So, the redox reaction between a large amount of Pt (IV) residue in the supernatant and Fe (III) was significantly successful, causing a low IFe(III)/IPt(IV) value. Under optimal conditions, we found that IFe(III)/IPt(IV) was linearly related to the logarithmic E. coli concentration with a low limit of detection (1.862 × 103 cfu mL−1). This devised ratiometric electrochemical method may develop into a powerful and effective means for the detection of E. coli in real samples, which may also be developed as a universal tool for another microorganism.
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CHEMICAL ENGINEERING JOURNAL
·
2019
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IF 8.355
Yuqi Geng,Jiaqi Li,Wenjuan Lu,Ning Wang,Zeyang Xiang,Yanzhao Yang
In this paper, superparamagnetic Fe 3 O 4 @SiO 2 -NH 2 nanoparticles were applied to adsorb Au(III)/Pd(II)/Pt(IV) in HCl medium. The successful synthesis of Fe 3 O 4 @SiO 2 -NH 2 was characterized through TEM, SEM and FT-IR. Electrostatic interaction between magnetic NPs and metal anions was proposed as the main adsorption mechanism by zeta potential analysis. Maximum adsorption capacities and adsorption behaviors under metal anions concentrations, acidity, NaCl, kinetic and isotherm models were investigated. Notably, the Fe 3 O 4 @SiO 2 -NH 2 shows the excellent acidity and salinity resistance on Au(III), Pd(II) adsorption. The separation routine among Au(III), Pd(II) and Pt(IV) was proposed. As investigated, Pt(IV) could be isolated due to the less adsorption amount onto Fe 3 O 4 @SiO 2 -NH 2 (≤1%). Then, the adsorbed Au(III) was eluted selectively by HCl + N-hexanol alcohol + ethanol + H 2 O 2 mixing solution. Then, the adsorbed Pd(II) was completely eluted by thiourea solution. The recovery efficiencies of Au(III), Pd(II) and Pt(IV) were kept over 92%, 97% and 94% respectively, during 5 turns of cycling separation experiments. Total loss amount of Fe is around 7%. Hence that, the particle demonstrates the good stability and high adsorption capacity, which possess great potential for practical Au(III), Pd(II) and Pt(IV) separation.
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Biomaterials Science
·
2017
·Vol. 5
·期 8
·1558-1566
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IF 4.21
Shao-Lu Li,Yingqin Hou,Yali Hu,Jin Yu,Wei Wei,Hua Lu
We describe here the synthesis and cell-selective delivery of a cationic Pt(IV)-backboned prodrug-like polymer P(DSP-DAEP). P(DSP-DAEP) features excellent aqueous solubility, unusually high (44.5%) drug loading, can be rapidly reduced to release the active cisplatin, and is more potent than its small molecular Pt(IV) precursor DSP. P(DSP-DAEP) can be formulated with an oppositely charged methoxyl poly(ethylene glycol)-block-poly(L-phosphotyrosine) (mPEG-b-PpY) to afford a polyion micelle (Pt-PIC) by taking advantage of polyelectrolyte coacervation. Preliminary in vitro cellular uptake and cytotoxicity assays indicate that Pt-PIC exhibits receptor (surface alkaline phosphatase)-dependent uptake and cytotoxicity. Overall, our results suggest a new approach to the improved therapeutic index of platinum-based anticancer drugs via cell-selective delivery.
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JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Dali Chen,Yunai Du,Xitong Wang,Huihong Li,Xinjiao Wu,Xiaoqin Kuang,Chunjiayu Li,Jianing Zhao,Yerong Xiong,Minjie Sun,Jiasheng Tu,Siyan Liu,Chunmeng Sun
Active-targeting nanomedicines have been widely employed in cancer treatment for increasing therapeutic index. However, the limited permeability caused by the binding site barrier (BSB) and size hindrances compromises their clinical antitumor efficacy in patients. Herein, learning from the liquid-liquid phase separation (LLPS) of bio-macromolecules, we report phase-separating glycopeptides (HEP) from polyhistidine (PHis) grafted hyaluronic acid (HA), which can sense the tumor extracellular pH and concomitantly overcome size and BSB dilemmas for enhanced tumor penetration. HEP aggregates into nanodroplets in solution at neutral pH. Upon reaching the acidic extracellular environment of tumors, the pH-responsive PHis triggers a phase separation, converting the coacervate nanodroplets into monomeric glycopeptides. This enables HEP conjugated with the platinum prodrug (HEPPt) to deeply penetrate into tumors by overcoming the BSB effect arising from the interaction between nanodroplets and cluster of differentiation 44 (CD44), as well as resolving the size challenges. Moreover, HEPPt in monomeric states exhibits promoted cellular uptake after pH-triggered phase separation, attributed to the transmembrane effect of exposed PHis. Subsequently, the rapid release of Pt(II), triggered by tumor intracellular reducing environment, exerts excellent antitumor activity. The phase-separating glycopeptides represent a promising platform for improving tumor penetration and intracellular delivery of therapeutic agents.
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