ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Shi-Ying Li,Hong Cheng,Wen-Xiu Qiu,Li-Han Liu,Si Chen,Ying Hu,Bo-Ru Xie,Bin Li,Xian-Zheng Zhang
In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT). It was found that after tail vein injection the ACPP-PpIX conjugate could accumulate effectively at the tumor site with the fluorescence enhancement which was beneficial for tumor diagnosis and image-guided PDT. After further administration with irradiation, both the solid tumor size and weight had a significant suppression (reduced by more than 90%) with a low systemic toxicity. This ACPP-PpIX conjugate delivery system activated by MMP-2 would be a promising strategy for tumor-targeted treatment.
研究领域:
癌症研究
·
药学科学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2015
·
IF 12.881
Kai Han,Shi-Bo Wang,Qi Lei,Jing-Yi Zhu,Xian-Zheng Zhang
Photodynamic therapy faces the barrier of choosing the appropriate irradiation region and time. In this paper, a matrix metalloproteinase-2 (MMP-2) responsive ratiometric biosensor was designed and synthesized for aggregation-induced emission (AIE)-guided precise photodynamic therapy. It was found that the biosensor presented the MMP-2 responsive AIE behavior. Most importantly, it could accurately differentiate the tumor cells from the healthy cells by the fluorescence ratio between freed tetraphenylethylene and protoporphyrin IX (PpIX, internal reference). In vivo study demonstrated that the biosensor could preferentially accumulate in the tumor tissue with a relative long blood retention time. Note that the intrinsic fluorescence of PpIX and MMP-2-triggered AIE fluorescence provided a real-time feedback which guided precise photodynamic therapy in vivo efficiently. This strategy demonstrated here opens a window in the precise medicine, especially for phototherapy.
研究领域:
癌症研究
·
治疗诊断学
·
生物医学工程
·
分子影像
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 9
·期 1
·221-237
·
IF 6.183
Zhiqiang Zhang,Anning Li,Xingqi Min,Qunqun Zhang,Jun Yang,Guo Chen,Meijuan Zou,Wei Sun,Gang Cheng
Chemotherapy and surgery are commonly used clinical treatments for breast cancer. However, unsatisfactory therapeutic effects, unavoidable side effects, and the removal of breast tissue during surgery are still major obstacles to be overcome during breast-cancer treatment. To overcome the aforementioned issues, a biomimetic and thermosensitive hydrogel encapsulating reactive oxygen species (ROS)-sensitive tegafur (TF)-protoporphyrin IX (PpIX) heterodimers (TTP) was prepared aimed at the strategy of synergizing chemotherapy and photodynamic therapy. TF was grafted onto the photosensitizer PpIX through ROS-sensitive thioether bonds. Under 630 nm laser irradiation, the ROS concentration in tumors was increased to help drug release. The “on-demand” drug release maximized the therapeutic effects of TF and effectively reduced its toxicity. Particularly, the ROS concentration was increased, and it was expected that the tumor-cell-killing abilities of ROS could be exploited. A hydrogel formed from temperature-sensitive chitosan and silk sericin was selected as a drug carrier, which formed a drug reservoir intratumorally after intratumoral injection. Intratumoral injection gave the drug precise and long-term release behavior, which allowed for the clever avoidance of various physical and biological barriers in vivo. In vivo and in vitro studies prove that the use of this TTP hydrogel provides a new attempt to overcome the many difficulties related to breast-cancer treatment simultaneously, and this study opens up new paths for breast-cancer treatment.
研究领域:
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Small
·
2015
·Vol. 11
·期 47
·6338-6346
·
IF 8.368
Jing Tan,Chuanyu Sun,Ke Xu,Changchun Wang,Jia Guo
5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn II coordination polymers as shells (Fe 3 O 4 @ALA-Zn II ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn II ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe 3 O 4 @ALA-Zn II microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe 3 O 4 @ALA-Zn II shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.
研究领域:
材料科学
·
纳米技术
·
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2018
·Vol. 95
·期 4
·1045-1051
·
IF 2.214
Xian Zhang,Longfei Chen,Lvfen Gao,Xuesong Gao,Nan Li,Yuwei Song,Xinke Huang,Shaoqiang Lin,Xiaoyu Wang
Comparison of the fluorescence intensity caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after low-dose 5-Aminolevulinic acid (ALA) injection combined with siRNA transfection was mediated by ultrasound microbubbles and polyethyleneimine (PEI) to explore the feasibility of the ultrasound microbubble technique as transfection agents. Knockdown of ferrochelatase (FECH) in human endometrial cancer xenografts in nude mice was performed by transfection with FECH-siRNA mediated by PEI and ultrasound microbubbles alone or in combination; then, low-dose ALA was injected. Subsequently, an in vivo animal imaging system was employed to detect the fluorescence intensity in xenografts. Red fluorescence was observed in xenografts given more than 6.25 mg kg −1 of ALA. When the dose of ALA was greater than 50 mg kg −1 , there was a significant difference in the fluorescence between tumor and other tissues. After the nude mice were transfected with siRNA and treated with low-dose ALA (1.0 mg kg −1 ), apparent PpIX fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles > PEI > ultrasound microbubbles. Ultrasound microbubbles in combination with PEI could generate a higher fluorescence intensity of PpIX than that obtained with ultrasound microbubbles or PEI alone, and ultrasound microbubbles could wholly or partially replace PEI under certain conditions.
研究领域:
肿瘤学
·
分子生物学
·
基因治疗
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Ping Tang,Meishuang Xing,Xinyue Xing,Qiao Tao,Wendai Cheng,Shengde Liu,Xiaoxu Lu,Liyun Zhong
Phototherapy, especially the photothermal therapy (PTT) and the photodynamic therapy (PDT), have become very promising in cancer treatment due to its low invasiveness and high efficacy. Both PTT and PDT involve the utilization of light energy, and their synergistic treatment should be a good solution for cancer treatment by ingenious design. The therapeutic effect of phototherapy is closely associated with the amount and location of anticancer-nanodrugs accumulated in tumor cells, and the receptor-mediated endocytosis should be an excellent candidate for enhancing anticancer-nanodrugs internalization. Surface enhanced Raman spectroscopy (SERS) imaging is suitable for tracing nanodrugs due to its high selectivity, sensitivity and reliability. In this paper, we hope to construct a receptor-mediated PTT/PDT synergistic anticancer nanodrugs and evaluate the corresponding efficacy through SERS tracing function. Here, the receptor-mediated PTT/PDT synergistic anticancer nanodrugs are prepared by the chemical modification of gold nanorods (GNRs), involving protoporphyrin IX (PpIX), 4-mecaptobenzoic acid (MBA), and folic acid (FA). The achieved results show that the receptor-mediated endocytosis can greatly facilitate the internalized amount and intracellular distribution of the nanodrugs, thus lead to the anti-cancer efficacy improvement. Importantly, this receptor-mediated PTT/PDT synergistic treatment with SERS tracing function will provide a simple and effective strategy for the design and application of anticancer phototherapy nanodrugs.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
光学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 26
·5255-5263
·
IF 6.331
Jiansheng Liu,Xueqin Qing,Qin Zhang,Ningyue Yu,Mengbin Ding,Zhaohui Li,Zhen Zhao,Zhiling Zhou,Jingchao Li
Photodynamic therapy (PDT) has provided a promising approach for the treatment of solid tumors, while the therapeutic efficacy is often limited due to the hypoxic tumor microenvironment, resulting in tumor metastasis. Herein, we report an oxygen-producing proenzyme hydrogel (OPeH) with photoactivatable enzymatic activity for PDT enabled metastasis-inhibiting combinational therapy of breast cancer. This OPeH based on alginate is composed of protoporphyrin IX (PpIX) conjugated manganese oxide (MnO2) nanoparticles, which act as both the photosensitizer and oxygen-producing agent, and singlet oxygen (1O2)-responsive proenzyme nanoparticles. In the hypoxic and acidic tumor microenvironment, MnO2 can generate 1O2 to promote PpIX-mediated PDT with an amplified 1O2 generation efficiency, which also triggers the cleavage of 1O2-responsive linkers and cascade activation of proenzymes for cancer cell death. This combinational therapy upon photoactivation not only greatly inhibited the tumor growth, but also suppressed lung metastasis in a mouse xenograft breast tumor model, which is impossible in the case of PDT alone. This study thus provides a proenzyme hydrogel platform with photoactivatable activity for metastasis-inhibiting cancer therapy with high efficacy and safety.
研究领域:
癌症治疗
·
纳米医学
·
生物医学工程
·
肿瘤微环境研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Yanyan Meng,Shaoqing Chen,Pengyin Li,Cheli Wang,Xinye Ni
Melanoma is a highly invasive and lethal skin cancer with a strong tendency to metastasize and has a poor prognosis. Radiotherapy is one of the important treatments for melanoma. In this study, monoglyceride solid lipid nanoparticles (MG SLNs) were wrapped with the B16-F10 cell membrane (B16 CM) for the fabrication of B16@MG. B16@MG had low toxicity and specifically targeted B16-F10 cells. B16-F10 tumor–bearing mouse model showed that indocyanine green (ICG) -loaded B16@MG achieved long-term accumulation in the tumor and facilitated the localization of the tumor boundary. MG SLNs were encapsulated with methyl 5-aminolevulinate (MLA) and desferrioxamine (DFO), and B16 CM was wrapped around their surfaces to obtain B16@MG–MLA–DFO.MLA was metabolized to protoporphyrin IX (PpIX) in the cells and DFO reduced the content of iron ion in the cells, blocked the biotransformation of PpIX, and promoted the accumulation of PpIX in the cells. The results of mitochondrial reactive oxygen species (ROS) and membrane potential detection showed that PpIX enhanced the generation of ROS, caused DNA and mitochondrial damage, and led to the apoptosis of tumor cells under radiotherapy. In B16-F10 tumor–bearing mice, B16@MG–MLA–DFO can improve the efficacy of radiotherapy and allow the integration of diagnosis and treatment.
研究领域:
肿瘤学
·
纳米技术
·
药理学
·
放射生物学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-14
·
IF 16.6
Fang Fang,Wang Sa,Song Yueyue,Sun Meng,Chen Wen-Cheng,Zhao Dongxu,Zhang Jinfeng
Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.
研究领域:
纳米医学
·
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Huihui Liu,Qing Wang,Jingru Guo,Kai Feng,Yiling Ruan,Zhihao Zhang,Xin Ji,Jigang Wang,Tao Zhang,Xiaolian Sun
Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an 89 Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome ( 89 Zr-ALA-Liposome-ART) for highly selective cancer therapy. 89 Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The 89 Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice via CR-PDT and chemotherapy. Combined with anti-PD-L1, the 89 Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.
研究领域:
药学
·
放射肿瘤学
·
纳米技术
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yanjuan Huang,Tao Zhang,Qin Wei,Zishan Zeng,Yujun Gong,Xiaoyu Xu,Meixu Chen,Chunshun Zhao
Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a “NIR-triggered ROS storage” intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.
研究领域:
眼科学
·
光动力疗法
·
生物医学工程
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuxuan Wei,Zuxiao Chen,Chuyu Huang,Hong Cheng,Xiaofeng Jiang,Shiying Li
Spatiotemporal downregulation of immune checkpoint provides a promising strategy to activate anti-tumor immunity. In this work, a breast cancer targeted photodynamic degrader (designated as EIpro) is constructed to activate immunotherapy through EGFR degradation mediated PD-L1 downregulation. To be specific, we develop a chimeric peptide, comprising the photosensitizer Protoporphyrin IX (PpIX) and EGFR targeting peptide (QRHKPRE), to encapsulate an EGFR inhibitor afatinib (AFA) forming nanomicelle, namely EIpro. EIpro has a favorable stability and uniform nanosize distribution, preferring to accumulate in EGFR overexpressed breast cancer cells to amplify the chemotherapeutic effect and photodynamic elimination behavior. More interestingly, photodynamic therapy (PDT) produced reactive oxygen species (ROS) is able to damage breast cancer cells and induce immunogenic cell death (ICD) to release tumor associated antigens (TAAs), thereby degrading the nearby EGFR to downregulate PD-L1 and activate anti-tumor immunity. Beneficially, the multi-synergistic effects of EIpro show a robust therapeutic efficacy against primary and metastatic breast cancer with negligible systemic toxicity. This work provides a spatiotemporal strategy for protein degradation, which might inspire the development of sophisticated nanomedicine for effective tumor treatment.
研究领域:
肿瘤学
·
免疫治疗
·
纳米医学
·
光动力疗法
·
癌症生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）