Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 44
·6924-6933
·
IF 5.047
Pei Liu,Weitao Yang,Lei Shi,Haiyan Zhang,Yan Xu,Peiru Wang,Guolong Zhang,Wei R. Chen,Bingbo Zhang,Xiuli Wang
Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy, and low side effects. Nevertheless, single modality therapy, either PTT or PDT, has limited clinical effectiveness in treating skin cancers. Thus, combined applications of PTT and PDT have been frequently reported; however, PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of biocompatible gold nanoclusters Au25(Capt)18 for the concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen, and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression of cSCC XL50 cells in vitro and the inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under 808 nm light irradiation, the tumor-cell-killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using an ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicated low adverse effects of the Au25(Capt)18 nanoclusters. Through this study, we report the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our study could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for the treatment of cancers.
研究领域:
肿瘤学
·
纳米技术
·
光疗
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Wei Li,Xiaomeng Guo,Fenfen Kong,Hanbo Zhang,Lihua Luo,Qingpo Li,Chunqi Zhu,Jie Yang,Yongzhong Du,Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2 , NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Yi Li,Zhiming Liu,Yuqing Hou,Guangcun Yang,Xixi Fei,Henan Zhao,Yanxian Guo,Chengkang Su,Zhen Wang,Huiqing Zhong,Zhengfei Zhuang,Zhouyi Guo
A multifunctional nanoplatform based on black phosphorus quantum dots (BPQDs) was developed for cancer bioimaging and combined photothermal therapy (PTT) and photodynamic therapy (PDT). BPQDs were functionalized with PEG chains to achieve improved biocompatibility and physiological stability. The as-prepared nanoparticles exhibite prominent near-infrared (NIR) photothermal and red-light-triggered photodynamic properties. The combined therapeutic application of PEGylated BPQDs were then performed in vitro and in vivo. The results demonstrate that the combined phototherapy significantly promote the therapeutic efficacy of cancer treatment in comparison with PTT or PDT alone. BPQDs could also serve as the loading platform for fluorescent molecules, allowing reliable imaging of cancer cells. In addition, the low cytotoxicity and negligible side effects to main organs were observed in toxicity experiments. The theranostic characteristics of PEGylated BPQDs provide an uplifting potential for the future clinical applications.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Junyi Zeng,Xinbo Huang,Yajie Yang,Jieyi Wang,Yuanchao Shi,Hui Li,Ning Hu,Bo Yu,Jing Mu
Controlling CRISPR/Cas9 gene editing at the spatiotemporal resolution level, especially for in vivo applications, remains a great challenge. Here, we developed a near-infrared (NIR) light-activated nanophotonic system (UCPP) for controlled CRISPR-Cas9 gene editing and synergistic photodynamic therapy (PDT). Lanthanide-doped upconversion nanoparticles are not only employed as carriers for intracellular plasmid delivery but also serve as the nanotransducers to convert NIR light (980 nm) into visible light with emission at 460 and 650 nm, which could result in simultaneous activation of gene editing and PDT processes, respectively. Such unique design not only achieves light-controlled precise gene editing of hypoxia-inducible factor 1α with minimal off-target effect, which effectively ameliorates the hypoxic state at tumor sites, but also facilitates the deep-seated PDT process with synergistic antitumor effect. This optogenetically activatable CRISPR-Cas9 nanosystem holds great potential for spatially controlled in vivo gene editing and targeted cancer therapy.
研究领域:
生物医学工程
·
分子生物学
·
基因治疗
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2024
·
IF 10.4
Yang Shuguang,Hu Lijun,Xiao Hong,Xiao Zecong,Shuai Xintao
Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTP-ICG, for photodynamic therapy (PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase (MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and MPO. Meanwhile, PDT efficiently incites immunogenic cell death (ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells (DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils (TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels, potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
研究领域:
癌症治疗
·
免疫学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xingchen Li,Ming Hao,Annan Liu,Lei Li,Maja D. Nešić,Bai Yang,Weiwei Liu,Quan Lin
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region, and its treatment is limited by hypoxia and inadequate oxygen supply. Continuous oxygen delivery combined with photodynamic therapy (PDT) is the key to addressing this issue. Here, a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform was designed to serve as an "oxygen pump" to alleviate tumor hypoxia for synergistic photodynamic/photothermal therapy (PTT). In this design, the photosensitizer chlorin e6 (Ce6) is covalently linked to the Au@Pt nanozyme for PDT treatment. The Au@Pt nanozyme exhibits catalase-like activity, continuously decomposing H 2 O 2 in the tumor microenvironment to enhance O 2 levels, thereby achieving efficient PDT. Furthermore, Au@Pt can perform PTT and increase oxygen levels under NIR-II light to further promote PDT. The Au@Pt nanozyme also exhibits peroxidase-like activity, generating ·OH for chemodynamic therapy (CDT). Additionally, HN-1 guides the direction of "sniping" OSCC, and its high specificity benefits Au@Pt-Ce6-HN-1 at the tumor site. Au@Pt-Ce6-HN-1 exhibits bright fluorescence (FL), strong CT signal, and photothermal imaging capabilities, laying the foundation for subsequent guided PDT/PTT. This nanoplatform, which combines advantages such as continuous oxygen production, tumor targeting, and multimodal imaging, is expected to provide valuable insights into the treatment of OSCC. Statement of Significance Accurate clinical diagnosis and treatment of OSCC are challenging. We report a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform, serving as an "oxygen pump" to guide photodynamic therapy (PDT) and photothermal therapy (PTT) for OSCC. This nanoplatform targets OSCC for preoperative CT diagnosis and offers fluorescence visualization for surgical navigation, demonstrating potential in clinical cancer detection and surgery guidance. This innovative approach addresses OSCC hypoxia and enhances treatment efficacy through continuous oxygen production, tumor targeting, and multimodal imaging, significantly improving patient outcomes in OSCC treatment.
研究领域:
癌症治疗
·
纳米技术
·
光疗
·
医学成像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Furong Liu,Tao He,Songlin Gong,Meiling Shen,Shuang Ma,Xianzhou Huang,Lu Li,Li Wang,Qinjie Wu,Changyang Gong
Combining the internal force-driven chemodynamic therapy (CDT) and the external energy-triggered photodynamic therapy (PDT) holds great promise to achieve an advanced anticancer effect based on reactive oxygen species (ROS). However, the insufficient oxy-substrates supply in tumor microenvironment, like hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ), is the Achilles heel that greatly restricts the efficacy of this ROS-based treatment. Herein, the construction of a c opper p e roxide-based tumor pH-re s ponsive a utocatalytic nano r eactor (CESAR), via an albumin-mediated biomimetic mineralization strategy is described. The decoration of human serum albumin endows the nanoreactor good hydrophilicity and biocompatibility, which is highly desired for the metal-based materials. Upon exposure to acidic tumor microenvironment, CESAR presents a pH-triggered disintegration with Cu 2+ , H 2 O 2 and O 2 generated instantly. The generated H 2 O 2 complements the hyperoxide deficiency and initiates a localized Fenton-like reaction with the assistance of Cu 2+ for highly toxic hydroxyl radicals (•OH) production for improving CDT. The evolved O 2 gas enables hypoxia relief for enhanced Ce6-mediated PDT. This H 2 O 2 /O 2 self-supplying strategy significantly amplifies the tumor oxidative damage and gains an optimal treatment outcome, which offers a new paradigm for optimizing the tumor therapeutic options limited by oxide or hyperoxide deficiency, not only for CDT/PDT, but also other oxy-substrates involved strategies. Statement of significance The shortage of oxy-substrates in the tumor microenvironment remains a great challenge for ROS-based cancer therapy. Herein, we introduce human serum albumin as a scaffold to stabilize copper peroxide nanomaterials for constant production of H 2 O 2 and O 2 to enhance chemodynamic/photodynamic therapy. The tumor pH-triggered H 2 O 2 /O 2 production and Cu 2+ release are confirmed, assuring the strategy of a highly precise, effective way to destroy tumor without any side effects. This work lends new and exciting insights into the engineering design of autocatalytic oxy-substrates self-supply nanoreactor for overcoming the bottlenecks, like the oxy-substrates deficiency of CDT/PDT and the poor stability of metal peroxides, to achieve highly effective chemodynamic/photodynamic therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4874-4889
·
IF 6.6
Shanshan Lin,Hui Chen,Rui Wang,Tongmeng Jiang,Rui Wang,Fabiao Yu
Bacterial infection seriously restricts the wound healing process due to severe inflammation and delayed wound healing. Unfortunately, the overuse or improper use of antibiotics leads to the advent of multidrug-resistant strains and intractable biofilms, severely affecting the therapeutic effect. Therefore, there is an urgent need to develop antibiotic-free strategies to accelerate the healing process of wounds with bacterial infection. Considering that single photothermal therapy (PTT) or photodynamic therapy (PDT) cannot fully meet the requirements of clinical sterilization and accelerating wound healing, herein, hollow silver–gold alloy nanoparticles immobilized with the photosensitizer molecule Ce6 (Ag@Au-Ce6 NPs) integrated with PTT and PDT are proposed for killing bacteria and accelerating wound healing. The photothermal conversion properties of Ag@Au-Ce6 NPs are obtained using an infrared thermal imager, and the generation of singlet oxygen (1O2) is verified with an 1O2 fluorescent probe DCFH-DA. Manipulated by near-infrared laser triggered mild hyperthermia and limited ROS amount, Ag@Au-Ce6 NPs could effectively kill bacteria that are free and colonized on the surface of wounded skin, promoting epithelium migration and vascularization, further accelerating wound healing, which showed great promise for biomedical application.
研究领域:
纳米技术
·
生物医学工程
·
光疗
·
伤口愈合
·
抗菌治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Yang Zhou,Fan Tong,Weilong Gu,Siqin He,Xiaotong Yang,Jiamei Li,Yue-Dong Gao,Huile Gao
Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1 α (HIF-1 α ) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo .
研究领域:
癌症治疗
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 13
·期 1
·273-281
·
IF 8.183
Zhang Tao,Jiang Zhenqi,Chen Libin,Pan Chunshu,Sun Shan,Liu Chuang,Li Zihou,Ren Wenzhi,Wu Aiguo,Huang Pintong
As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H 2 O 2 in the tumor site to O 2 , thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T 1 -MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.
研究领域:
肿瘤学
·
放射学
·
纳米医学
·
治疗诊断学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 33
·13617-13627
·
IF 6.7
Lei Li,Guoqing Zhu,Wencheng Xu,Man Wang,Yulin Xie,Zixian Bao,Manlin Qi,Minghong Gao,Chunxia Li
The emergence of multidrug-resistant (MDR) bacterial infections calls for novel strategies for effective bacterial inhibition and wound healing. Phototherapeutic approaches are promising in treating bacterial infection because of their high efficiency, noninvasiveness, and few side effects; however, their antibacterial effect is limited by the formation of biofilms in wounds. Herein, we report novel composite nanoparticles (mPt/ICG-αA NPs) combining mesoporous platinum (mPt) nanoparticles, indocyanine green (ICG) and α-amylase (αA) for combating MDR bacteria and treating wound infection, which integrates a triple bacterial inhibition mechanism arising from the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and α-amylase enzymatic activities. The combination of mPt and ICG significantly enhances the effect of PTT and the temperature can be increased up to 80.8 °C to induce efficacious bacterial degeneration. Meanwhile, mPt/ICG-αA (mPIA) NPs with a low concentration of 25 μg mL−1 exhibited a remarkable catalase activity (CAT) and could continuously decompose endogenous H2O2 into O2 in a hypoxic microenvironment, thereby enhancing the PDT effect to achieve broad-spectrum bactericidal activity. mPIA NPs showed excellent MDR antibacterial efficiency against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and the bactericidal rate reached up to 99.0% and 97.2% with single 808 nm near-infrared light irradiation, respectively. mPIA NPs also exhibited an excellent ability to destroy biofilms and biocompatibility. Animal experiments further suggested that mPIA NPs could achieve the successful repairment of wounds infected with S. aureus in living systems, while this platform demonstrated negligible toxicity towards mice. Considering the superior performances of mPIA NPs, the synergistic αA-CAT-PDT-PTT boosted therapeutic activity presented in the current work provides a promising method to effectively fight against biofilm-related infectious diseases and wound healing.
研究领域:
纳米技术
·
光疗
·
抗菌治疗
·
伤口愈合
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200237
·
IF 4.6
Yan-Mei Li,Xiang Zhou,Xin-Yu Li,Jia-Qi Huang,Zi-Wen Qiu,Ren-Jiang Kong,Ni Yan,Shi-Ying Li,Hong Cheng
Oxygen-dependent photodynamic therapy (PDT) holds unique advantages on tumor treatment by inducing cell apoptosis, but it is often limited owing to the unfavorable tumor microenvironments. In this study, a self-delivery O 2 -ecomonizer (designated as CeTam) is prepared to relieve hypoxia and reverse antiapoptotic pathway for enhanced photodynamic tumor therapy. Based on Chlorin e6 (Ce6) and Tamoxifen (Tam), CeTam is assembled through intermolecular hydrophobic interaction without any vehicles. Nanosized CeTam has an enhanced stability and improved drug delivery efficiency, which prefers to accumulate at tumor tissue for effective cellular uptake. More importantly, CeTam can effectively inhibit mitochondrial respiration to relieve hypoxia and reduce Bcl-2 expression to reverse antiapoptotic pathway. As a result, this self-delivery O 2 -ecomonizer successfully regulates the unfavorable tumor microenvironments to enhance the PDT efficacy on tumor elimination. Taken together, this work reports a multifunctional nanoplatform by a simple self-assembly strategy to remedy the deficiencies of PDT on hypoxic tumor treatment, which can advance the development of individualized biomedicine for precise tumor therapy.
研究领域:
癌症治疗
·
药理学
·
纳米技术
·
分子生物学
✓ 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）