Research
·
2022
·
IF 11.036
Qingfei Zhang,Xiaocheng Wang,Gaizhen Kuang,Yunru Yu,Yuanjin Zhao
Biomedical scaffolds have shown great success in postsurgical tumor treatment; their current efforts are focusing on eradicating residual tumor cells and circulating tumor cells and simultaneously repairing postoperative tissue defects. Herein, we report a novel photopolymerized 3D scaffold with Pt(IV) prodrug initiator to achieve the desired features for tumor comprehensive therapy. The Pt-GelMA scaffold was fabricated from the microfluidic 3D printing of methacrylate gelatin (GelMA) bioinks through a Pt(IV)-induced photocrosslinked process without any other additional photoinitiator and chemotherapeutic drug. Thus, the resultant scaffold displayed efficient cell killing ability against breast cancer cells in vitro and significantly inhibited the local tumor growth and distant metastases on an orthotopic postoperative breast cancer model in vivo. Besides, benefiting from their ordered porous structures and favorable biocompatibility, the scaffolds supported the cell attachment, spreading, and proliferation of normal cells in vitro; could facilitate the nutrient transportation; and induced new tissue ingrowth for repairing tissue defects caused by surgery. These properties indicate that such 3D printing scaffold is a promising candidate for efficient postoperative tumor treatment in the practical application.
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Xiaoran Deng,Yunlu Dai,Jianhua Liu,Ying Zhou,Ping'an Ma,Ziyong Cheng,Yinyin Chen,Kerong Deng,Xuejiao Li,Zhiyao Hou,Chunxia Li,Jun Lin
Combining the multi-modal medical imaging with cancer therapy in one single system has attracted the great interests for theranostic purpose. In this paper, CaF 2 :Yb 3+ /Er 3+ /Mn 2+ -poly(2-Aminoethyl methacrylate) (UCHNs-PAMA) hybrid microspheres were successfully fabricated. The synthetic route to the nanocomposite based on a facile hydrothermal method for fabrication of hollow upconversion (UC) nanospheres at first and then post-filling the PAMA interiorly through photo-initiated polymerization. The UCHNs showed orange fluorescence under 980 nm near infrared (NIR) laser excitation , which provided the upconverting luminescence (UCL) imaging modality . Meanwhile, the presence of functional Mn 2+ and Yb 3+ offered the enhanced T 1 -weighted magnetic resonance (MR) and computed tomography (CT) imaging, respectively. Thanks to introducing amine groups-containing PAMA inside the hollow nanospheres, the Pt(IV) pro-drug, c,c,t-Pt(NH 3 ) 2 Cl 2 (OOCCH 2 CH 2 COOH) 2 (DSP), can be conveniently bonded on the polymer network to construct a nanoscale anti-cancer drug carrier. The UCHNs-PAMA-Pt(IV) nanocomposite shows effective inhibition for Hela cell line via MTT assay . In contrast, Pt(IV) pro-drug and UCHNs-PAMA microspheres behave little cytotoxicity to Hela cells. This should be attributed the fact that the anti-cancer ability can be recovered only when Pt(IV) pro-drug was reduced to Pt(II)-drug in cellular environment. Furthermore, the in vivo experiments on small mice also confirm that the hybrid microspheres have relatively low toxic side effects and high tumor inhibition rate. These findings show that the multifunctional hybrid microspheres have potential to be used as UCL/MR/CT tri-modal imaging contrast agent and anti-cancer drug carriers.
研究领域:
纳米医学
·
生物材料
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癌症治疗
·
医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Qingfei Zhang,Xiaocheng Wang,Gaizhen Kuang,Yuanjin Zhao
Multimodal treatment modalities hold great potential for cancer therapy, thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms. Herein, we present a novel trans, trans,trans -[Pt(N 3 ) 2 (OH) 2 (py) 2 ] (Pt(IV)) prodrug-initiated hydrogel microparticles (M ICG-Pt ) with indocyanine green (ICG) encapsulation by microfluidics for efficiently synergistic chemo-, photothermal (PTT) and photodynamic therapy (PDT). The employed Pt(IV) could not only serves as an initiator to generate azidyl radical (N 3 • ) for photo-polymerization of methacrylate gelatin (GelMA) matrix, but also be reduced to high cytotoxic platinum(II) (Pt(II)) species for tumor chemotherapy. The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species (ROS) productivity endows the M ICG-Pt with effective PTT/PDT performances upon near-infrared (NIR) light irradiation. In addition, benefiting from the production of oxygen during the photo-activation process of Pt(IV), the PDT efficacy of ICG-laden M ICG-Pt could be further enhanced. Based on these advantages, we have demonstrated that the M ICG-Pt could significantly eliminate cancer cells in vitro , and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy, PTT, and PDT. These results indicate that such Pt(IV)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms, holding great prospects for cancer therapy.
研究领域:
癌症治疗
·
药学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Kun Shang,Dongsheng Tang,Minhui Cui,Hongyi Hou,Bing Xiao,Jinjian Liu,Ruoshi Zhang,Rui Kuai,Jianfeng Liu,Haihua Xiao,Fan Huang,Jianliu Wang
Cisplatin is a first-line, broad-spectrum anti-tumor drug used to treat various types of cancer. However, immune-suppressive tumor microenvironments (TME) are often induced by cisplatin. Here, a first synthetic high-density lipoprotein (sHDL) nanodisc, referred as sHDL@Pt, is engineered to load a Pt(IV) prodrug (C2-Pt(IV)-C12), inducing a 2.2-fold increase in dsDNA release compared to cisplatin. This further activates the innate immune system through the cGAS-STING pathway. Using near-infrared II fluorescence imaging and single photon emission computed tomography imaging technology, it is found that sHDL@Pt can be effectively accumulated in tumor sites. The sHDL@Pt can induce severe DNA damage, which subsequently results in a more pronounced activation of the cGAS-STING pathway, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. This work introduces a novel approach for delivering Pt(IV) prodrug that effectively initiates and activates innate immunity through the activation of the cGAS-STING pathway.
研究领域:
纳米医学
·
肿瘤学
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免疫治疗
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药理学
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 27
·5903-5911
·
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.
研究领域:
纳米技术
·
癌症治疗
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药物递送系统
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2020
·Vol. 7
·期 5
·1220-1228
·
IF 5.958
Xiao-Jing Ding,Ran Zhang,Rui-Ping Liu,Xue-Qing Song,Xin Qiao,Cheng-Zhi Xie,Xiu-He Zhao,Jing-Yuan Xu
A series of Pt(IV) compounds comprising a special short-chain fatty acid (a histone deacetylase inhibitor) and 5-FU (a thymidylate synthase inhibitor) were prepared and bio-evaluated for their antiproliferative activity using the MTT assay. The assembled compounds 11–15, as triple-prodrugs, exhibited a potent anti-cancer activity. In particular, compounds 14 and 15 both with valproic acid (VPA) showed higher potent cytotoxicity against the tested cancer cells, whereas lower cytotoxicity toward normal human umbilical vein endothelial cells than the free drugs involved. Compound 14, as a representative for further study, rapidly enhanced the cellular accumulation in a time-dependent manner, significantly induced the DNA-damage, cell cycle blocking at the S phase, and cell apoptosis as well as suppressed migration in HeLa. Most strikingly, compound 14 simultaneously regulated the TS, HDAC and γH2AX factors, suggesting a synergistic action of 5-FU, VPA and CDDP to increase the drug effects.
研究领域:
药理学
·
肿瘤学
·
化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yupeng Wang,Yuwei Cong,Manying Cai,Xiaoling Liang,Lina Wang,Dongfang Zhou
Polyprodrug nanomedicines hold great potential for combating tumors. However, the functionalization of polyprodrug nanomedicines to improve therapeutic efficacy is restricted by conventional polymerization methods. Herein, we fabricated a charge-conversional click polyprodrug nanomedicine system by metal-free azide-alkyne cycloaddition click polymerization (AACCP) for targeted and synergistic cancer therapy. Specifically, Pt(IV) prodrug-backboned diazide monomer , DMC prodrug-pendent diazide monomer, dialkyne-terminated PEG monomer and azide-modified folate were click polymerized to obtain the target polyprodrug (P1). P1 could self-assemble into nano-micelles (1-NM), where PEG was the hydrophilic shell with folate on the surface, Pt(IV) and DMC prodrugs as the hydrophobic core. Taking advantage of PEGylation and folate-mediated tumor cell targeting, 1-NM achieved prolonged blood circulation time and high tumor accumulation efficiency. Tumor acidic microenvironment-responsive cleavage and cascade activation of pendant DMC prodrug induced surface charge conversion of 1-NM from negative to positive, which promoted tumor penetration and cellular internalization of the remaining 1-NM. After internalization into tumor cells, the reduction-responsive activation of Pt(IV) prodrug to Pt(II) further showed synergetic effect with DMC for enhanced apoptosis . This first designed charge-conversional click polyprodrug nanomedicine exhibited targeted and synergistic efficacy to suppress tumor proliferation in living mice bearing human ovarian tumor model.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Zhe Li,Xiao-Meng Liu,Fei Tan,Jia-Qian Wang,Xin Qiao,Yu-Kuan Feng,Jing-Yuan Xu,Ji-Hui Hao
Convincing evidence revealed that some platinum-based drugs could stimulate immunological recognition, thereby inducing immunogenic cell death (ICD). Indoleamine-2,3-dioxygenase (IDO) is overexpressed in tumors, which caused exhaustion of tryptophan (T-cell energy) and constructed an immunosuppressive tumor microenvironment. Herein, considering IDO inhibition to improve chemotherapy, a series of IDOi-Pt(IV) prodrugs were designed to not only target DNA and IDO but also facilitate tumor-antigen exposure and immunomodulation. The optimal IDOi-Pt(IV) prodrugs (named compound 10) significantly enhanced intracellular accumulation 22.4-fold and cytotoxicity 61.75-fold superior to cisplatin in HeLa cells. Moreover, immunofluorescence and enzyme-linked immunosorbent assays revealed that 10 induced reactive oxygen species-mediated endoplasmic reticulum stress and secretion of damage-associated molecular patterns, thereby presenting ICD effects. Molecular docking, enzyme inhibition, and Western blot assays demonstrated that 10 could effectively inhibit IDO1 and reverse immunosuppression, as further verified by mixed leukocyte reactions. In vivo tests showed that 10 exhibited high-efficiency and low-toxicity antitumor effects compared to cisplatin, presenting successful chemoimmunotherapy.
研究领域:
肿瘤学
·
免疫学
·
药理学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2022
·Vol. 9
·期 14
·3470-3483
·
IF 7.779
Xiao-Meng Liu,Zhe Li,Xin-Rui He,Rui-Ping Liu,Zhong-Ying Ma,Xin Qiao,Shu-Qing Wang,Jing-Yuan Xu
The combination of endocrine therapy and chemotherapy is an attractive approach for treating breast cancers. Aromatase inhibitors (AIs) are the first-line drugs for postmenopausal ER-positive breast cancer and adjuvant therapy drugs for early stages of breast cancer. In this paper, we employed the FDA-approved aromatase inhibitor aminoglutethimide (AG) to design and prepare a new class of multi-targeting Pt(IV) prodrugs (aminoplatins 1–3) by utilizing the targeting, estrogen-manipulating, and chemo-sensitizing effects of the aromatase inhibitor. Aminoplatin 3, as a representative, exhibited an enhanced anticancer activity up to 190-fold greater than the parent Pt(II) drug cisplatin, and 3 had less toxicity to normal cells, displaying higher anticancer efficacy and a superior therapeutic index compared to those of cisplatin. Moreover, aminoplatin 3 could enhance intracellular accumulation, induce remarkable DNA damage, inhibit migration and metastasis, and result in S phase cell cycle arrest and apoptosis in ER-positive MCF-7 cells. Besides, molecular docking results showed that 3 simultaneously occupies the heme iron-binding domain and the ASD-binding site of aromatase by a highly efficient dual-binding pattern to aromatase, which further displayed a striking anti-estrogenic effect by significant downregulation of CPY19A1 and ERα in ER-positive MCF-7 cells. Most strikingly, our in vivo anticancer evaluation data also provided evidence that 3 effectively inhibited tumor growth and attenuated kidney toxicity compared to cisplatin in MCF-7 xenografted BALB/c nude mice. Our results suggest that the anticancer activity of aminoplatins is mechanistically distinct from that of the conventional platinum drugs, and modifying platinum drugs with aromatase inhibitors may represent an improved modality for the treatment of advanced postmenopausal breast cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
高影响因子
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