JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Hui-Zhen Yang,Yue Hu,Jia-Jia Chen,Rui-Mo Zhao,Lin Pu,Xiao-Qi Yu,Ji Zhang
Nitric oxide (NO) combined with photodynamic therapy (PDT) is a promising tumor treatment method. Herein, the cationic lipid DPNO(Zn) was developed as co-delivery carrier of NO and photosensitizer Chlorin e6 (Ce6). The target CNO lipid nanoparticles (LNPs) were obtained by solvent exchange method as a NO/PDT combination therapy platform, and biocompatible polymer γPGA could be easily coated to form PCNO for in vivo applications. Fluorescence spectra and confocal imaging experiments showed that the Ce6-loaded LNPs could release NO rapidly under low power UV irradiation with fluorescence self-reporting ability. On the other hand, under the irradiation of 660 nm laser, the LNPs could effectively produce singlet oxygen ( 1 O 2 ). In vitro and in vivo antitumor assays showed that the combination treatment of NO/PDT was more effective in tumor growth inhibition compared with individual NO or PDT treatment. Mechanism studies of NO/PDT combined therapy revealed that 1 O 2 could increase the level of p53 protein, thus activating the caspase 3 apoptosis pathway. And the rapid release of NO could amplify the effect of this pathway by reducing the level of HIF-1α. The NO and 1 O 2 released under laser irradiation could not only directly damage DNA and mitochondria, resulting in tumor cell dysfunction, but also induce the upregulation of iNOS to further enhance the gas therapy efficiency. This study proved that the light-triggered NO/ 1 O 2 generation system can be used as an effective NO/PDT synergistic therapy platform for cancer treatment.
研究领域:
药学
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生物医学工程
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肿瘤学
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纳米技术
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Qi Liu,Chenxi Tang,Jiafeng Liu,Yuan Gao,Lin Peng
Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis and a dysregulated host response, leading to soft-tissue destruction and alveolar bone loss. Antibacterial photodynamic therapy (aPDT) can rapidly suppress pathogens via light-triggered reactive oxygen species (ROS). Here, we report zirconium-based porphyrinic metal–organic framework (MOF) nanoparticles, PCN-224, as a bifunctional platform that couples early antibacterial aPDT with subsequent immunomodulation within the periodontal microenvironment. PCN-224 demonstrated excellent biocompatibility in vitro and in vivo . Under 660 nm irradiation, PCN-224 effectively generated singlet oxygen ( 1 O 2 ) and reduced Porphyromonas gingivalis burden. After uptake by RAW 264.7 macrophages, PCN-224 attenuated lipopolysaccharide-induced inflammation by lowering intracellular ROS levels, restoring superoxide dismutase activity, decreasing nitric oxide release, suppressing NF-κB signaling, accompanied by reduced IL-6, IL-1β, and iNOS and partial recovery of anti-inflammatory mediators. In a ligature-induced mouse model, local PCN-224 injection combined with 660 nm illumination decreased inflammatory infiltration and alleviated alveolar bone resorption. Collectively, PCN-224 provides a time-sequenced antibacterial-to-anti-inflammatory therapeutic effect and represents a potential MOF-enabled strategy for periodontitis management.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhencheng Sun,Jiaxin Wang,Minghui Xiao,Kaiyu Wu,Cheng Wang,Hao Fu,Shuyi Lv,Linqi Shi,Chunlei Zhu
Type-I photodynamic therapy (PDT), valued for its reduced oxygen requirement, generates highly cytotoxic •OH radicals. However, conventional strategies for developing type-I photosensitizers (PSs) are complex and involve intricate organic synthesis. Herein, we present a novel strategy to alter the generation of reactive oxygen species (ROS) by simply manipulating the twisting degree of donor–acceptor (D−A) type aggregation-induced emission (AIE) PSs. Specifically, natural saturated fatty acids are employed to modulate the twisting state of AIE PSs, with higher doping ratios yielding more twisted structures and increased type-I ROS generation. In contrast, fatty acids with higher crystallinity promote planar structures and type-II ROS generation. Theoretical calculations suggest that AIE PSs with highly twisted structures lead to a prominent reduction in Δ E ST and effective separation of electron−hole pairs, thereby favoring efficient intersystem crossing and charge transfer. The PDT system primarily driven by type-I ROS exhibits efficient bactericidal activity against clinically drug-resistant bacteria, which remarkably accelerates the recovery of bacteria-infected wounds in mice. This study demonstrates the first example of modulating ROS generation type by manipulating the twisting degree of D−A type AIE PSs, eliminating the need for intricate molecular design and organic synthesis. The proposed strategy opens up new avenues for advancing PDT applications.
研究领域:
光动力治疗
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材料科学
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生物医学工程
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化学
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细菌学
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DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 22
·4261-4273
·
IF 7.571
Hui Guo,Fangzhe Liu,Enqi Liu,Shanshan Wei,Wenbo Sun,Baoqiang Liu,Guoying Sun,Lehui Lu
Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA–Cys–PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA–Cys–PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM−1 s−1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.
研究领域:
纳米技术
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癌症治疗
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磁共振成像（MRI）
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药物递送系统
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光动力疗法
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Qin Shi,Yuqing Tong,Yuzhao Zheng,Yanqi Liu,Tingjie Yin
The heterogeneity of tumor microenvironment leads to uneven distribution of bio-stimuli. Thus, the multi-site delivery efficiency of responsive drug delivery systems (DDS) inner tumor was always limited. Herein, we proposed a combination strategy of photodynamic therapy (PDT) with ROS-responsive nanosystem which was constructed from dextran-phenylboronic acid pinacol ester conjugates. This combination utilized PDT to amplify and homogenize tissular oxidation level, and achieve effective multi-site response and release of multi-target drugs like gambogic acid (GA). Our research demonstrated the successful preparation of GA and protoporphyrin IX (PpIX) co-loaded nanoparticles, and the PDT-mediated spatiotemporal controlled multi-site drug release in simulated conditions. Furthermore, data from in vitro and in vivo researches on B16F10 cells, HUVEC, and B16F10-bearing C57BL/6 mice potently confirmed the enhanced multi-mechanism regulations of GA mediated by the effective and homogeneous tumoral release. This tactic based on bio-stimuli amplification and homogenization proposes a paradigm to maximize the potency of multi-target drugs.
研究领域:
癌症治疗
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纳米医学
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Bing Cao,Yingfei Ma,Jian Zhang,Yanan Wang,Yating Wen,Yun li,Ruixue Wang,Donghai Cao,Ruiping Zhang
Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H 2 O 2 , while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.
研究领域:
医学
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材料科学
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牙科学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 17
·5824-5840
·
IF 6.843
Mengchao Ding,Kai Shao,Lijuan Wu,Yuping Jiang,Bing Cheng,Lili Wang,Jinsheng Shi,Xiaoying Kong
Nitric oxide (NO) gas treatment offers a promising strategy for tumor therapy; however, its practical application is still limited due to its poor efficacy and biotoxicity which were caused by gas leakage during blood delivery. Herein, a nano-platform (CMH-OBN) composed of chlorin e6-melanin-hyaluronic acid nanoparticles (Ce6-MNP-HA, CMH) and oxidized bletilla striata polysaccharide microcapsules (Oxi-BSP) carrying NO donors was prepared for responsive and cascaded release of NO, reactive oxygen species (ROS) and its secondary metabolite reactive nitrogen species (RNS) in tumor sites. Melanin not only endowed CMH with good photothermal properties, but also helped Ce6 to produce a large number of ROS under near-infrared (NIR) irradiation. OBN microcapsules, which were sensitive to ROS, can release NO donors under the stimulation of ROS released by CMH nanoparticles under NIR irradiation and can further release NO in the tumor microenvironment (TME) with high expression of glutathione (GSH). NO could further up-regulate soluble guanylate cyclase-cyclic guanosine monophosphate (sGC-cGMP) signal pathways to relieve hypoxia, thus further enhancing the photodynamic therapy (PDT). Moreover, the cascaded release of ROS and NO could produce RNS with higher lethality, which could sequentially initiate the cellular apoptotic procedure and promote immunotherapy by activating T cells at the tumor sites. More interestingly, the CMH-OBN nano-platform could supply magnetic resonance imaging (MRI) and infrared photothermal imaging guidance for tumor therapy. In conclusion, the development of a CMH-OBN nano-platform provides a satisfactory demonstration by combining NO therapy with photothermal therapy (PTT), PDT and immunotherapy for the treatment of cancer.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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DOI
PubMed
高影响因子
BIOPHYSICAL CHEMISTRY
·
2025
·
IF 2.2
Changqiu Ma,Anqi Han,Daheng Jiang,Qiuyan Wang,Linghui Zeng,Lixin Zhu,Mingya Yang,Xiaoliang Xu
Photodynamic therapy utilizes photosensitizer to generate reactive oxygen species (ROS) under irradiation of light for anticancer. However, due to the strong absorption of visible light by tissues and organs, photodynamic therapy meets challenges in deep tissues. Herein, we propose an upconversion-driven photodynamic therapy combined with chemodynamic therapy based on UCNP@SiO 2 @Fe 3 O 4 @MC540. Upon the excitation of 980 nm laser, the visible emission of upconversion nanoparticles activates MC540 to produce ROS, which is enhanced by Fe 3 O 4 through magnetic field modulation. Subsequently, Fe 3 O 4 degrades under acidic conditions to produce ·OH via Fenton-reaction for chemodynamic therapy. The in vitro and in vivo experiments indicate that the two-step cooperative strategy exhibits significant anticancer efficacy. Besides, Finite Difference Time Domain (FDTD) simulation reveals that the enhancement stems from surface electric field and light absorption. It offers a deeper understanding of phototherapeutic process.
研究领域:
生物医学工程
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Luyao Xu,Jing Feng,Shihao Xu,Mingli Jin,Xianyue Bai,Hui Zhang,Minghui Zhu,Shengmin Lin,Jiaxing Song,Cuixia Lu
Multimodal targeted combination therapy that harnesses synergistic effects has emerged as a transformative paradigm in cancer therapy, progressively replacing traditional monotherapy. Herein, we report a tumor microenvironment (TME)-responsive multifunctional nanoplatform Cu-Ce6@DHA NPs (CCD NPs), which is self-assembled through the coordination of Cu²⁺, the antitumor drug dihydroartemisinin (DHA), and the photosensitizer chlorin e6 (Ce6). This nanoplatform enables the near-infrared-triggered combination of cuproptosis and ferroptosis for tumor treatment. Upon internalization by tumor cells, these nanoparticles undergo glutathione (GSH)-triggered disintegration, releasing their encapsulated payloads within the TME. The released Ce6 mediates potent photodynamic therapy (PDT) under laser irradiation, and DHA undergoes GSH-dependent activation to generate cytotoxic reactive oxygen species (ROS) and suppresses glutathione peroxidase 4 (GPX4), thereby amplifying ferroptotic cell death. Concurrently, the released copper ions deplete intracellular GSH and further inhibit GPX4, which exacerbates lipid peroxidation and promotes ferroptosis. Notably, the intracellular accumulation of copper ions disrupts mitochondrial metabolism by destabilizing iron-sulfur cluster (Fe-S) proteins and inducing oligomerization of lipoylated lipoylated dihydrolipoamide S-acetyltransferase (DLAT), ultimately triggering cuproptosis. Therefore, our findings establish a novel nanoplatform that simultaneously exploits metabolic vulnerabilities (via cuproptosis), redox imbalances (via ferroptosis), and photodynamic effects, providing a promising multimodal therapeutic strategy for cancer treatment.
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DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2024
·
IF 6.1
Xuwen Da,Yunli Xu,Lei Wang,Xiulian Liu,Yatong Peng,Yao Wu,Wanpeng Zhou,Wentao Wang,Xuesong Wang,Qian-Xiong Zhou
Traditional photodynamic therapy (PDT) is almost ineffective against deeply seated tumors due to the limited penetration depth of external light. The development of chemiexcited PDT is promising to address this issue, but it is still challenging to construct simple, efficient and targeted chemiexcited PDT systems. In this work, CPPO (bio(3,5,6-trichloro-2-n-pentyloxycarbonylphenyl) oxalate) and [Ru(phen)2(PIP-OCH3)](PF6)2 (Ru3, where phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4-methoxy phenyl)-1Himidazo[4,5-f][1,10]phenanthroline) with efficient photo-catalytic NADH oxidation were co-encapsulated with DSPE-PEG 2000 to form Ru3/CPPO@PEG nanoparticles (NP3). Once internalized by cancer cells, Ru3 can be excited by the chemical energy produced by the reaction between CPPO and endogenous H2O2. The subsequent oxidation of intracellular NADH and generation of H2O2 in situ by excited Ru3 will further promote the sustained occurrence of chemical reaction, realizing a self-enhanced chemiexcited PDT. NP3 could effectively deplete intracellular NADH, inhibit ATP synthesis, increase H2O2 content, and produce reactive oxygen species (ROS) within cancer cells, thus exhibited efficient chemiexcited PDT activity against various cancer cells. Notably, minimal cytotoxicity was observed towards normal cells. Good therapeutic effects against subcutaneously implanted and lung metastatic tumors were also observed for NP3. The current findings may provide new sights for development of novel chemiexcited PDT.
研究领域:
光动力疗法
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癌症研究
·
纳米技术
·
生物化学
·
药学
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产品关联
DOI
高影响因子
ACS Omega
·
2022
·
IF 4.132
Ting Yan,Gulinigaer Alimu,Lijun Zhu,Huimin Fan,Linxue Zhang,Zhong Du,Rong Ma,Shuang Chen,Nuernisha Alifu,Xueliang Zhang
High treatment accuracy is the key to efficient cancer treatment. Photodynamic therapy (PDT) and photothermal therapy (PTT) are two kinds of popular, precise treatment methods. The combination of photodynamic and photothermal therapy (PDT/PTT) can greatly enhance the precise therapeutic efficacy. In this work, protoporphyrin IX (PpIX) was selected as the PDT agent (photosensitizer), and new indocyanine green (IR-820) was selected as the PTT agent. Further, the two kinds of theranostic agents were encapsulated by biological-membrane-compatible liposomes to form PpIX-IR-820@Lipo nanoparticles (NPs), a new kind of PDT/PTT agent. The PpIX-IR-820@Lipo NPs exhibited good water solubility, a spherical shape, and high fluorescence peak emission in the near-infrared spectral region (700–900 nm, NIR). The cellular toxicity of PpIX-IR-820@Lipo NPs for human cervical cancer cells (HeLa) and human cervical epithelial cells (H8) was detected by the CCK-8 method, and low cytotoxicity was observed for the PpIX-IR-820@Lipo NPs. Then, the excellent cellular uptake of PpIX-IR-820@Lipo NPs was confirmed by laser scanning confocal microscopy. Moreover, the PDT/PTT property of PpIX-IR-820@Lipo NPs was illustrated via 2′,7′-dichlorofluorescin diacetate (DCFH-DA) and annexin V-fluorescein isothiocyanate (annexin V-FITC), as indicator probes. The PDT/PTT synergistic efficiency of PpIX-IR-820@Lipo NPs on HeLa cells was verified, exhibiting a high efficiency of 70.5%. Thus, the novel theranostic PpIX-IR-820@Lipo NPs can be used as a promising PDT/PTT synergistic theranostic nanoplatform in future cervical cancer treatment.
研究领域:
癌症研究
·
纳米技术
·
光疗
·
生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Yan Shi,Jinrui Li,Jiaxuan Zhao,Lu Liu,Ruimin Zhan,Dandan Jing,Xiaoya Wang,Dongwei Ma,Junmin Lee,Zhiguo Wang,Ming Kong
Pathological scars are fibrotic disorders arising from aberrant wound healing. PDT is effective but limited by a dense matrix, hypoxia, and post-PDT excessive ROS-induced secondary inflammation. To address this, a NIR-switchable ROS-regulatory liposome (ICC@Lip) with CaO2 NPs (oxygenation to strengthen PDT) and Cu5.4O nanozymes (ROS scavenging) was developed. In addition, inspired by Cyperaceae stems and triangular arrows, a highly penetrable biomimetic microneedle platform loaded with ICC@Lip and collagenase I (ICC@Lip/HPMN) was constructed to realize efficient transdermal cargo delivery and diffusion into a rigid pathological scar matrix. The puncture resistance of ICC@Lip/HPMN was only 56.4% that of conventional rectangular pyramid microneedles, with an effective puncture rate of 96% in mouse skin. In vitro, under NIR irradiation-mediated PDT/PTT, ICC@Lip significantly alleviated intracellular hypoxia and related fibrotic indicators, achieving a cytotoxicity rate of 93.71% against myofibroblasts─1.49-fold higher than that of the IR808 alone group (62.74%)─while reducing M2 macrophage polarization and TGF-β secretion. Notably, timely post-PDT ROS clearance decreased M1 polarization of macrophages and reduced the release of over 50% of inflammatory cytokines. In rabbit ear, a hypertrophic scar model exhibited that ICC@Lip/HPMN reduced the scar elevation index from 3 to 1.7, significantly alleviating collagen deposition and inflammation. The antifibrotic efficacies were majorly exerted through cross-downregulation of TGF-β, IL-4, and toll-like receptor signaling pathways. This study provided a promising adaptive therapeutic strategy of self-strengthened PDT coupling ROS precise regulation for pathological scars.
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DOI
高影响因子
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