ACS Nano
·
2024
·
IF 15.8
Yang Li,Qianqian Zhang,Zhen Sun,Mingjie Rong,Chunhuan Jiang,Lehui Lu
The utilization of alkyl radicals (•R) for hypoxic tumor therapy has great prospects due to its O2-independence and high reactivity. However, correlational initiators for in vivo activation remain scarce. Here, we report that ultrasound excitation of oleic acid-capped BaTiO3 (OA@BaTiO3) can result in an •R cascade and hence a means to conquer hypoxic tumors. Mechanistic studies find that the •R signal disappears when OA@BaTiO3 undergoes acid washing post-treatment, which is a common procedure for removing the unwanted byproduct BaCO3. Combined with the infrared spectrum analysis, acid treatment was proven to weaken the peaks at 2840–2970 cm–1 characteristic of -CH2- and terminal -CH3 stretching vibration of OA. There is compelling evidence that high temperature thermal oxidation of OA involves the generation of •R. Thus, acid washing is considered to remove the loosely bound yet catalytically active OA. And piezoelectric BaTiO3, a potential electron–hole redox catalyst, can sensitize these OA molecules and disintegrate them to •R. This unexpected discovery provides us with a distinctive mentality to seek diverse •R initiators for tumor ablation, as well as an additional perspective on the postprocessing of synthetic materials.
研究领域:
材料科学
·
肿瘤学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Li Yang,Gu Xinquan,Yu Fan
Hypoxia in the tumor microenvironment induces radioresistance in cancer cells, which reduces the treatment efficiency of radiotherapy. Therefore, it is critical to produce sufficient oxygen to alleviate hypoxia to enhance the effect of ionizing radiation. Here, we constructed nanorod-shaped PdTe nanoenzymes to overcome hypoxia and promote the effects of thermoradiotherapy. Both palladium and tellurium are high-Z elements, which interacted with X-rays to generate more DNA radicals in the tumor regions. Moreover, PdTe nanoenzyme could catalyze the conversion of intratumoral overexpressed H2O2 to oxygen, alleviating hypoxia in the tumor regions. Photothermal therapy mediated by PdTe nanoenzymes not only ablated tumors but also accelerated the blood flow, in turn, modulating hypoxia. With good biocompatibility, PdTe nanoenzyme exhibited remarkable oxygen generation ability both in vitro and in vivo, indicating potential ability for radiosensitization. Further investigation using MBT-2 cells and MBT-2 tumor-bearing mice demonstrated that PdTe nanoenzyme could effectively enhance the treatment efficiency of radiotherapy. Thus, our work presented a novel nanoenzyme to overcome hypoxia in tumors for effective thermoradiotherapy.
研究领域:
肿瘤学
·
生物医学工程
·
放射医学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Ying Xu,Peng Chen,Lei Tang,Xiaojun Zhang,Feng Shi,Xuyang Ning,Jingli Bi,Yang Qu,Hongfei Liu
Most chemotherapy agents have serious side effects due to lack of tumor targeting, which affects their clinical application. In addition, as an essential characteristic of malignant tumor, hypoxia is attracting exclusive research focus regarding its non-invasive real-time tracing in novel targeting delivery system. Herein, we designed a mixed micelle with tumor targeting and hypoxia responsiveness for tumor therapy and imaging. In particular, the dual-modified mix micelles were self-assembled by folic acid (FA) and 2-(2-nitroimidazole) ethylamine (NI) conjugated polymers , in which paclitaxel (PTX) and quantum dots (QDs) were co-loaded into the hydrophobic core. The drug loaded micelles showed satisfactory drug encapsulation, good storage stability, and sustained release properties. In vitro cell experiments showed that the mixed micelles exhibited enhanced cytotoxic effect and improved the cellular uptake, especially under hypoxic conditions, which was due to the FA mediated active targeting effect and NI induced hypoxic responsive release. In vivo experiments further proved that the mixed micelles possessed outstanding tumor targeting and hypoxia responsive properties. Furthermore, the drug loaded micelles showed excellent anti-tumor effect and can realize real-time in vivo imaging. This work demonstrates that the dual-modified mixed micelles co-loading with PTX and QDs might provide a novel approach for tumor therapy and imaging.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 3
·e0121293
·
IF 3.234
Yun Zeng,Yang Liu,Jin Shang,Jingwen Ma,Rong Wang,Lei Deng,Youmin Guo,Fan Zhong,Mingfeng Bai,Shaojuan Zhang,Daocheng Wu
Objectives
To utilize phosphorescence to monitor hypoxic microenvironment in solid-tumors and investigate cancer chemotherapeutic effects in vivo .
Methods
A hypoxia-sensitive probe named BTP was used to monitor hypoxic microenvironment in solid-tumors. The low-dose metronomic treatment with cisplatin was used in anti-angiogenetic chemotherapeutic programs. The phosphorescence properties of BTP were detected by a spectrofluorometer. BTP cytotoxicity utilized cell necrosis and apoptosis, which were evaluated by trypan blue dye exclusion and Hoechst33342 plus propidium iodide assays. Tumor-bearing mouse models of colon adenocarcinoma were used for tumor imaging in vivo . Monitoring of the hypoxic microenvironment in tumors was performed with a Maestro 2 fluorescence imaging system. Tumor tissues in each group were harvested regularly and treated with pathological hematoxylin and eosin and immunohistochemical staining to confirm imaging results.
Results
BTP did not feature obvious cytotoxicity for cells, and tumor growth in low-dose metronomic cisplatin treated mice was significantly inhibited by chemotherapy. Hypoxic levels significantly increased due to cisplatin, as proven by the expression level of related proteins. Phosphorescence intensity in the tumors of mice in the cisplatin group was stronger and showed higher contrast than that in tumors of saline treated mice.
We develop a useful phosphorescence method to evaluate the chemotherapeutic effects of cisplatin. The proposed method shows potential as a phosphorescence imaging approach for evaluating chemotherapeutic effects in vivo , especially anti-angiogenesis.
研究领域:
肿瘤学
·
医学影像学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 13
·4727-4740
·
IF 6.6
Pengchao Ji,Jinghua Chen,Hao Wang,Linfei Shi,Xudong Tang,Yanhong Duo
Many approaches have been employed to relieve hypoxia in solid tumors to enhance sensitivity to radiotherapy (RT), including O2 delivery or hydrogen peroxide (H2O2) decomposition strategies. To date, however, these modalities have been restricted by poor O2 loading, rapid O2 leakage, and limited endogenous H2O2 levels. To overcome these limitations, we therefore sought to develop an effective approach for the oxygen-independent treatment of hypoxic tumors. In this study, we designed a novel black phosphorus quantum dot (BPQD)/Escherichia coli (E. coli) hybrid system (BE) capable of facilitating the photothermal therapy (PTT) of hypoxic tumors. A simple electrostatic adsorption approach was used to conjugate BPQDs to E. coli. BE is capable of reliably targeting hypoxic tumors and mediating PTT. BPQDs in BE can directly facilitate X-ray-mediated radiosensitization of tumors, thereby achieving significant RT efficacy in response to lower doses of radiation, effectively and specifically damaging hypoxic tumor tissues to suppress the growth of tumors. Our results highlight this BE system as a novel approach to tumor radiosensitization with great potential for clinical application.
研究领域:
肿瘤学
·
生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2016
·Vol. 27
·期 4
·1604258
·
IF 11.382
Zhifang Ma,Xiaodan Jia,Jing Bai,Yudi Ruan,Chao Wang,Jianming Li,Mengchao Zhang,Xiue Jiang
Premature leakage of photosensitizer (PS) from nanocarriers significantly reduces the accumulation of PS within a tumor, thereby enhancing nonspecific accumulation in normal tissues, which inevitably leads to a limited efficacy for photodynamic therapy (PDT) and the enhanced systematic phototoxicity. Moreover, local hypoxia of the tumor tissue also seriously hinders the PDT. To overcome these limitations, an acidic H 2 O 2 -responsive and O 2 -evolving core–shell PDT nanoplatform is developed by using MnO 2 shell as a switchable shield to prevent the premature release of loaded PS in core and elevate the O 2 concentration within tumor tissue. The inner core SiO 2 -methylene blue obtained by co-condensation has a high PS payload and the outer MnO 2 shell shields PS from leaking into blood after intravenous injection until reaching tumor tissue. Moreover, the shell MnO 2 simultaneously endows the theranostic nanocomposite with redox activity toward H 2 O 2 in the acidic microenvironment of tumor tissue to generate O 2 and thus overcomes the hypoxia of cancer cells. More importantly, the Mn(ΙΙ) ion reduced from Mn(ΙV) is capable of in vivo magnetic resonance imaging selectively in response to overexpressed acidic H 2 O 2 . The facile incorporation of the switchable MnO 2 shell into one multifunctional diagnostic and therapeutic nanoplatform has great potential for future clinical application.
研究领域:
生物医学工程
·
肿瘤治疗学
·
纳米医学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Dapeng Chen,Yunyun Tang,Jiawei Zhu,Jiaojiao Zhang,Xuejiao Song,Wenjun Wang,Jinjun Shao,Wei Huang,Peng Chen,Xiaochen Dong
Highly specific and effective cancer phototherapy remains as a great challenge. Herein, a smart nanoplatform (TENAB NP) sequentially responsive to light, low pH and hypoxia is demonstrated for multi-mode imaging guided synergistic cancer therapy with negligible skin phototoxicity . Upon 808-nm laser irradiation , TENAB NPs can generate hyperthermia to melt the phase change material (PCM-LASA) coat and thereafter release chemo-drug tirapazamine (TPZ). Meanwhile, under acidic pH, photosensitizer ENAB would turn “off” its charge-transfer state, generating prominent 1 O 2 for photodynamic therapy (PDT) and heat for photothermal therapy (PTT), respectively. Accompanied with PDT-induced hypoxia, the released TPZ can be activated into its cytotoxic form for tumor cells killing. Notably, owing to phase change material LASA coat and ENAB's pH sensitivity, TENAB NPs show negligible photosensitization to skin and normal tissues. As the multi-stimuli responsive mechanism, TENAB NPs demonstrate a promising future in cancer photo-chemo theranostics with excellent skin protection.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Lili Qian,Qian Li,Zhenshan Ding,Kejun Luo,Jiamin Su,Jiawei Chen,Guangying Zhu,Zhihua Gan,Qingsong Yu
Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.
研究领域:
肿瘤学
·
放射生物学
·
药学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Tingyu Sun,Jingnan Li,Yinglin Zhou,Chao Zeng,Chengyan Luo,Xirui Luo,Huanan Li
High intensity focused ultrasound (HIFU) has attracted considerable attention as a noninvasive, efficient, and economic therapeutic modality for solid tumors. However, HIFU surgery has its intrinsic limitation in completely ablating tumors, leading to residual tumor tissue. Furthermore, the severely hypoxic environment ensuring after surgery can exacerbate the unrestricted proliferation and metabolism of residual tumor cells, leading to tumor recurrence and metastasis. To address these limitations, a versatile HIFU-specific metal-organic framework nanosystem (called ADMOFs) is developed by coordinating hypoxia-activated prodrug AQ4N, Mn 2+ , and DOX based on the postoperative response to changes in the tumor microenvironment. ADMOFs loaded with AQ4N/Mn 2+ exhibited remarkable tumor-targeting behavior in vivo and enhanced photoacoustic/magnetic resonance imaging effects, enabling more accurate guidance for HIFU surgery. After surgery, the ADMOFs exploited the severely hypoxic tumor environment induced by HIFU, overcoming hypoxia-associated drug resistance, and inducing immunogenic cell death. Finally, it effectively inhibited tumor growth and eliminated lung metastasis. Transcriptome studies revealed that this strategy significantly up-regulated genes involved in apoptosis, cell cycle, and HIF-1 signaling pathway while downregulating genes related to tumor proliferation and metastasis. These findings suggest that combining hypoxia-activated chemo-immunotherapy with HIFU is a promising strategy for enhancing cancer theranostics.
研究领域:
肿瘤学
·
医学影像学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Meng Lyu,Mingzhu Chen,Lujie Liu,Daoming Zhu,Xianjia Wu,Yang Li,Lang Rao,Zhirong Bao
Rational: Interstitial brachytherapy (BT) is a promising radiation therapy for cancer; however, the efficacy of BT is limited by tumor radioresistance. Recent advances in materials science and nanotechnology have offered many new opportunities for BT. Methods: In this work, we developed a biomimetic nanotheranostic platform for enhanced BT. Core-shell Au@AuPd nanospheres (CANS) were synthesized and then encapsulated in platelet (PLT)-derived plasma membranes. Results: The resulting PLT/CANS nanoparticles efficiently evaded immune clearance and specifically accumulated in tumor tissues due to the targeting capabilities of the PLT membrane coating. Under endoscopic guidance, a BT needle was manipulated to deliver appropriate radiation doses to orthotopic colon tumors while sparing surrounding organs. Accumulated PLT/CANS enhanced the irradiation dose deposition in tumor tissue while alleviating tumor hypoxia by catalyzing endogenous H 2 O 2 to produce O 2 . After treatment with PLT/CANS and BT, 100% of mice survived for 30 days. Conclusions: Our work presents a safe, robust, and efficient strategy for enhancing BT outcomes when adapted to treatment of intracavitary and unresectable tumors.
研究领域:
肿瘤学
·
纳米医学
·
放射治疗学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Shuaijie Ding,Zeming Liu,Chunyu Huang,Ning Zeng,Wei Jiang,Qing Li
Intratumoral hypoxia significantly constrains the susceptibility of solid tumors to oxygen-dependent photodynamic therapy (PDT), and effort to reverse such hypoxia has achieved limited success to date. Herein, we developed a novel engineered bacterial system capable of targeting hypoxic tumor tissues and efficiently mediating the photodynamic treatment of these tumors. For this system, we genetically engineered Escherichia coli to express catalase, after which we explored an electrostatic adsorption approach to link black phosphorus quantum dots (BPQDs) to the surface of these bacteria, thereby generating an engineered E. coli/BPQDs (EB) system. Following intravenous injection, EB was able to target hypoxic tumor tissues. Subsequent 660 nm laser irradiation drove EB to generate reactive oxygen species (ROS) and destroy the membranes of these bacteria, leading to the release of catalase that subsequently degrades hydrogen peroxide to yield oxygen. Increased oxygen levels alleviate intratumoral hypoxia, thereby enhancing BPQD-mediated photodynamic therapy. This system was able to efficiently kill tumor cells in vivo, exhibiting good therapeutic efficacy. In summary, this study is the first to report the utilization of engineered bacteria to facilitate PDT, and our results highlight new avenues for BPQD-mediated cancer treatment.
研究领域:
癌症治疗
·
纳米医学
·
基因工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Xiaoyu Huang,Wei Zhang,Yaowei Peng,Lu Gao,Fu Wang,Lan Wang,Xunbin Wei
Oxygen consumption but hypoxic tumor environment has been considered as the major obstacle in photodynamic therapy. Although oxygen-supplied strategies have been reported extensively, they still suffer from the complicated system and unsatisfied PDT efficiency. Herein, one-component layered nickel silicate nanoplatforms (LNS NPs) are successfully synthesized using natural vermiculite as the silica source, which can simultaneously supply oxygen (O2) and generate superoxide radicals (O2–•) under near-infrared irradiation. The appropriate electron band structure endows LNS NPs with attractive optical properties, where the bandgap edges determine the performance of redox activity and spectral response characteristic. Evidenced by both in vitro and in vivo investigations, LNS NPs can generate sufficient superoxide radicals under 660 nm laser irradiation to induce tumor cell apoptosis even in a severe hypoxic environment, which benefits from self-supplied oxygen. Besides, the photoacoustic oxy-hem imaging and histologic assay further demonstrated that the generated oxygen can relieve the inherent intratumoral hypoxia. Therefore, LNS NPs not only serve as superoxide radical generator but also produce oxygen to modulate hypoxia, suggesting that it can be used for superoxide radical-mediated photodynamic therapy with enhanced antitumor effect.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）