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ACS Applied Polymer Materials · 2025 · IF 4.7

ICG@ZIF@HA Nanoparticles and GO-Loaded Freeze-Drying Microneedles Mediated PDT/PTT Dual-Modal Phototherapeutic for Efficient Bacterial Biofilm Elimination

Yanyan Zheng,Yueyue Xie,Xu Dong,Shulin Shen,Gensuo Zheng,Jiaqi Weng,Qinying Yan

Biofilms, which are dense bacterial aggregates that form protective adhesion layers on surfaces, are associated with chronic wound infections, severe acne, and various other bacterial infection sites. However, the increasing antibiotic resistance of bacteria within biofilms and the limited penetration capacity of conventional treatments pose significant therapeutic challenges. To address these issues, we engineered a freeze-drying microneedle system integrating indocyanine green-loaded ZIF-8/hyaluronic acid nanoparticles (ICG@ZIF@HA NPs) and graphene oxide (GO) for dual-modal phototherapy. Notably, the microneedles demonstrated robust mechanical strength, enabling penetration through 140 μm-thick Staphylococcus aureus biofilms. Subsequently, the disruption of the biofilm’s structural integrity facilitated the release of ICG@ZIF@HA NPs from the microneedle tips into deeper biofilm regions. Moreover, the nanoparticles exhibited pH-triggered release kinetics, with over 80% of ICG released at pH 5.5 within 2 h, and generated reactive oxygen species (ROS) under 808 nm near-infrared (NIR) irradiation. Meanwhile, the GO in the backing provided localized hyperthermia, reaching 55 °C within 500 s under NIR exposure. By combining ROS generation and bacterial membrane disruption, the microneedle system achieved a synergistic antimicrobial effect, effectively inhibiting bacterial growth and eliminating biofilms under NIR irradiation. Thus, this study establishes a robust foundation for integrating antimicrobial therapy with microneedle technology, offering a safer and more efficient strategy for biofilm eradication.

研究领域: 纳米医学 · 光疗 · 抗菌治疗 · 药物递送系统 · 生物材料 · 生物膜研究 · 生物医学工程
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ACS Applied Bio Materials · 2024 · IF 4.6

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing

Jiawei Bao,Jiayu Mi,Yi Xia,Han Gui,Haixue Jia,Dianyu Wang,Hongjing Luo,Linzhu Su,Jiamin Zhang,Jinjian Liu,Jianfeng Liu

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme–mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

研究领域: 材料科学 · 生物医学工程 · 药学 · 伤口愈合 · 传染病学
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 7 ·1846-1857 · IF 6.331

A Gd-doped polydopamine (PDA)-based theranostic nanoplatform as a strong MR/PA dual-modal imaging agent for PTT/PDT synergistic therapy

Yiyao Pu,Yuda Zhu,Zi Qiao,Nini Xin,Suping Chen,Jing Sun,Rongrong Jin,Yu Nie,Hongsong Fan

Based on widely used photoacoustic imaging (PAI) and photothermal properties of polydopamine (PDA), a multifunctional Gd–PDA-Ce6@Gd-MOF (GPCG) nanosystem with a core–shell structure and strong imaging ability was constructed. Benefitting from the metal–organic framework (MOF) structure, GPCG nanoparticles (NPs) showed enhanced magnetic resonance imaging (MRI) ability with high relaxation rates (r1 = 13.72 mM−1 s−1 and r2 = 216.14 mM−1 s−1). The MRI effect of Gd ions combined with the PAI effect of PDA, giving GPCG NPs a dual-modal imaging ability. The core, mainly composed of PDA and photodynamic photosensitizer chlorin e6 (Ce6), achieved photothermal/photodynamic therapy (PTT/PDT) synergistic performance. Besides, to overcome the unexpected release of Ce6, the MOF shell realized pH-sensitive release and a high local concentration. Through in vivo studies, we concluded that GPCG NPs show a good inhibitory effect on tumor growth. In conclusion, we successfully obtained a GPCG theranostic nanoplatform and paved the way for subsequent design of imaging guided therapeutic nanostructures based on metal-doped PDA.

研究领域: 纳米技术 · 生物医学工程 · 诊疗学 · 影像与治疗
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BIOMACROMOLECULES · 2021 · IF 6.988

Hypoxia-Sensitive Zwitterionic Vehicle for Tumor-Specific Drug Delivery through Antifouling-Based Stable Biotransport Alongside PDT-Sensitized Controlled Release

Tingjie Yin,Xuxin Chu,Jiejie Cheng,Jinlai Liang,Jianping Zhou,Meirong Huo

A hypoxia-sensitive zwitterionic vehicle, DHigh-PEI-(A+P), with the ability for antifouling-mediated, stable biotransport and a photodynamic therapy (PDT)-sensitized hypoxic response for spatiotemporal controlled drug release, was developed for the tumor-specific delivery of chemotherapeutics and biomacromolecules. The amphiphilic DHigh-PEI-(A+P) was constructed from a betaine monomer (DMAAPS), a photosensitizer (PpIX), and an azobenzene-4,4′-dicarboxylic acid-modified polyethylenimine. Herein paclitaxel (PTX) was selected as a common model drug to verify the functions of the designed polymer. First, DHigh-PEI-(A+P) was demonstrated to spontaneously coassemble with PTX in aqueous solution with high drug loading (>35%). The desirable antifouling ability of DHigh-PEI-(A+P) was independently verified by efficient 4T1 endocytosis in serum alongside systemic tumor targeting. Furthermore, PpIX-mediated PDT was verified to aggravate and homogenize a hypoxic microenvironment at the cell and tissue levels for a sharp responsive disassembly of DHigh-PEI-(A+P) and thus a robust drug release in a well-controlled manner. As a result, DHigh-PEI-(A+P) amplified the therapeutic outcome of PTX on orthotopic 4T1 mouse models with minimal collateral damage. We proposed that DHigh-PEI-(A+P) may serve as a tailor-designed universal vehicle for the tumor-specific delivery of drugs with distinct physicochemical properties.

研究领域: 癌症治疗 · 药物递送系统 · 生物医学工程 · 纳米技术 · 药学科学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Copper-Nitrogen-Coordinated Carbon Dots: Transformable Phototheranostics from Precise PTT/PDT to Post-Treatment Imaging-Guided PDT for Residual Tumor Cells

Lizhen Zhang,Aijia Yang,Changping Ruan,Bang-Ping Jiang,Xiaolu Guo,Hong Liang,Wen-Shuo Kuo,Xing-Can Shen

Phototheranostics has attracted considerable attention in the fields of cancer diagnosis and treatment. However, the complete eradication of solid tumors using traditional phototheranostics is difficult because of the limited depth and range of laser irradiation. New phototheranostics enabling precise phototherapy and post-treatment imaging-guided programmed therapy for residual tumors is urgently required. Accordingly, this study developed a novel transformable phototheranostics by assembling hyaluronic acid (HA) with copper-nitrogen-coordinated carbon dots (CDs). In this transformable nanoplatform, named copper-nitrogen-CDs@HA, the HA component enables the specific targeting of cluster determinant (CD) 44-overexpressing tumor cells. In the tumor cells, redox glutathione converts Cu(II) (cupric ions) into Cu(I) (cuprous ions), which confers the novel transformable functionality to phototheranostics. Both in vitro and in vivo results reveal that the near-infrared-light-photoactivated CuII-N-CDs@HA could target CD44-overexpressing tumor cells for precise synergistic photothermal therapy and photodynamic therapy. This study is the first to observe that CuII-N-CDs@HA could escape from lysosomes and be transformed in situ into CuI-N-CDs@HA in tumor cells, with the d9 electronic configuration of Cu(II) changing to the d10 electronic configuration of Cu(I), which turns on their fluorescence and turns off their photothermal properties. This transformable phototheranostics could be used for post-treatment imaging-guided photodynamic therapy on residual tumor cells. Thus, the rationally designed copper-nitrogen-coordinated CDs offer a simple in situ transformation strategy for using multiple-stimulus-responsive precise phototheranostics in post-treatment monitoring of residual tumor cells and imaging-guided programmed therapy.

研究领域: 癌症治疗 · 生物医学工程 · 纳米医学
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BIOMACROMOLECULES · 2024 · IF 5.5

Multifunctional Nanoplatform for Single NIR Laser-Regulated Efficient PDT/PTT/Chemotherapy

Yu Chen,Zhentan Lu,Dong Wang

The combination of phototherapy and chemotherapy with superior advantages is a promising strategy for cancer therapy. However, combination therapy is generally regulated by two different wavelengths of light or other stimuli, which results in complex operations and inevitable systemic side effects, even affecting therapeutic efficacy. Herein, we design a signal NIR light-regulated nanoplatform via the self-assembly process of reactive oxygen species (ROS)-sensitive prodrug (DTD), human serum albumin (HSA), and IR780 for combined photothermal/photodynamic therapy and chemotherapy. Upon 808 nm laser irradiation, IR780 in nanoparticles generates abundant ROS and a significant photothermal effect to achieve photothermal/photodynamic therapy. Meanwhile, the generating ROS further cleans up the thioketal link to release DOX for chemotherapy. Hence, signal NIR light can effectively control the process of combination therapy. In vivo and in vitro experiment results demonstrate that the multifunctional nanoparticles exhibit excellent antitumor efficacy via the combination of phototherapy and chemotherapy controlled by a signal NIR laser. Overall, the signal NIR light-regulated nanoparticles with combination therapy performance provide a versatile platform for enhancing antitumor efficacy.

研究领域: 肿瘤学 · 纳米医学 · 生物材料
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Combinative dual-nanoparticle assembly improves oxygen-autarky PDT efficacy in hypoxic tumors

Shengyu Liu,Yi Wang,Sijia Yao,Qian Li,Chenkai Sun,Yishan Chen,Junqiu Ye,Weisong Li,Dong Wu,Jianping Zhou,Hao Cheng,Yang Ding

O 2 -dependent photodynamic therapy (PDT) represents an efficient strategy for tumor ablation, but its therapeutic efficacy is critically compromised in hypoxic tumors. To tackle unsatisfying O 2 supplying, we design a dual-nanoparticle assembly for O 2 source-carrying photosensitizer delivery to enhance PDT efficiency. Structurally, catalase (CAT) is condensed into nanocapsules for biostability and sustainable O 2 supplying, and indocyanine green (ICG) is dispersed in polymeric nanospheres to prevent photobleaching and self-aggregation. According to O 2 demands, CAT nanocapsules are covalently conjugated with ICG nanospheres in an optimal ratio to facilitate O 2 enrichment around photosensitizer, together with hyaluronic acid (HA) decoration for advanced tumor targeting, thereby achieving O 2 -autarky PDT in hypoxic tumors. In comparison to simply-mixed delivery of CAT nanocapsules and ICG nanospheres, dual-nanoparticle assembly enables co-accumulation of CAT and ICG at the tumor site via HA receptor recognition, followed by CAT-catalyzed O 2 -generation and in situ O 2 -supplying to the surrounded ICG nanospheres, thereby satisfying O 2 demands of hypoxic tumors during PDT. Consequently, the nanoassembly significantly increases the intra-tumoral oxyhemoglobin saturation to 31.68% and yields tumor inhibition of 85.94% in the orthotopic breast cancer models. Collectively, this study provides a dual-nanoparticle assembly design of O 2 source-carrying photosensitizer to achieve O 2 -autarky PDT and establishes a new paradigm for O 2 -dependent PDT in hypoxic tumors.

研究领域: 生物医学工程 · 肿瘤学 · 药剂学
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Penicillin G amidase-activatable near-infrared imaging guiding PDT of bacterial infections

Chao Zhao,Wanlu Sun,Baojin Tan,Dan Su,Yi Liu

The antibiotic therapy usually leads to the bacterial resistance, and the traditional photosensitizer was in “always on” state with damage to normal tissue. Fortunately, the activatable near-infrared photosensitizer has a high depth of tissue penetration, and can be specifically released with low side effect. Therefore, we designed and synthesized a penicillin G acylase (PGA) activable photosensitizer (NFh-PGA), which could be activated to produce NFh-OH. NFh-OH can product singlet oxygen ( 1 O 2 ) under near-infrared light 730 nm excitation, and have an excellent antibacterial effect in vitro and in vivo . The probe accelerates the healing of bacterial infection wounds by near-infrared imaging guiding PDT. This work provides a strategy for the integrated design of diagnosis and treatment of bacterial infection.

研究领域: 医学 · 药学 · 生物技术
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Applied Materials Today · 2021 · IF 10.041

Palliating the escalated post-PDT tumor hypoxia with a dual cascade oxygenation nanocomplex

Ying Li,Chunjiao Wu,Yuewen Zhai,Ran Han,Ruoyu Gu,Yuying Ma,Peng Gao,Zhiyu Qian,Yueqing Gu,Siwen Li

Despite widespread researches engaging in optimizing the efficacy of PDT, the exacerbated hypoxia phenotype in the tumor tissue after PDT has always been neglected. Moreover, the ramifications of aggravated post-PDT hypoxia for tumor microenvironment (TME) have only been poorly investigated. Herein, we report a dual cascade oxygenation strategy with primary oxygenating to promote PDT and re-oxygenation to ameliorate post-PDT hypoxia. In this strategy, nanocomplex [email protected] @Ce6 was synthesized, which consisted of red blood cell-derived vesicles (RDV) as the outer shell and CAT-PCL nano-assembly encapsulating with Ce6 as the inner core. Our results showed that [email protected] @Ce6 amplified the PDT treatment through the first oxygenation and relieved tumor hypoxia by the second reoxygenation following PDT. On the other hand, the dual cascade oxygenation strategy also could effectively unleash the suppression onto the tumor immune microenvironment, which could further constrain tumor development and metastasis. In addition, [email protected] @Ce6 also exhibited excellent biocompatibility and superior stability in vivo. This dual cascade oxygenation strategy may provide a promising and pragmatic platform for clinical applications.

研究领域: 肿瘤学 · 纳米技术 · 生物医学工程 · 免疫治疗
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Fe/MOF based platform for NIR laser induced efficient PDT/PTT of cancer

Liang Zixing,Li Xiaofeng,Chen Xiaofang,Zhou Jiawei,Li Yanan,Peng Jianhui,Lin Zhousheng,Liu Gai,Zeng Xiancheng,Li Cheng,Hang Lifeng,Li Hailiang

Introduction: Photodynamic therapy (PDT) and photothermal therapy (PTT) are widely used in the treatment of tumors. However, their application in the treatment of clinical tumors is limited by the complexity and irreversible hypoxia environment generated by tumor tissues. To overcome this limitation, a nanoparticle composed of indocyanine green (ICG) and Fe-MOF-5 was developed.Methods: We prepared F-I@FM5 and measured its morphology, particle size, and stability. Its enzyme like ability and optical effect was verified. Then we used MTT, staining and flow cytometry to evaluated the anti-tumor effect on EMT-6 cells in vitro. Finally, the anti-tumor effect in vivo has been studied on EMT-6 tumor bearing mice.Results: For the composite nanoparticle, we confirmed that Fe-MOF-5 has the best nanozyme activity. In addition, it has excellent photothermal conversion efficiency and generates reactive oxygen species (ROS) under near-infrared light irradiation (808 nm). The composite nanoparticle showed good tumor inhibition effect in vitro and in vivo, which was superior to the free ICG or Fe-MOF-5 alone. Besides, there was no obvious cytotoxicity in major organs within the effective therapeutic concentration.Discussion: Fe-MOF-5 has the function of simulating catalase, which can promote the decomposition of excessive H2O2 in the tumor microenvironment and produce oxygen to improve the hypoxic environment. The improvement of tumor hypoxia can enhance the efficacy of PDT and PTT. This research not only provides an efficient and stable anti-tumor nano platform, but also has broad application prospects in the field of tumor therapy, and provides a new idea for the application of MOF as an important carrier material in the field of photodynamic therapy.

研究领域: 癌症治疗 · 纳米技术 · 光动力疗法 · 光热疗法 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

A hierarchical supramolecular nanozyme platform for programming tumor-specific PDT and catalytic therapy

Baoxuan Huang,Jia Tian,Zepeng Cui,Sihao Weng,Weitao Wang,Xiaoze Jiang,Weian Zhang

Supramolecular chemistry as a promising tool bridges the gap between conveniently synthetic processes and multifunction through reversible noncovalent interactions. Herein, a supramolecular nanoplatform, AuP-PS , is built by flexible and reversible supramolecular interactions between pillar[5]arene-capped gold nanoparticles ( AuP s) and porphyrin-containing “V” shape block copolymers ( PS ). The biosafety of AuP-PS was greatly improved by the formation of supramolecular complexes. Taking advantage of gradient pH changes in the tumor microenvironment (TME), AuP-PS can first disassemble into single AuP-PS nanoparticles due to the pH-sensitive DPA units of PS under pH = 6.5 and enter into the in-depth tumor sites. Whereafter, single AuP-PS nanoparticles completely dissociate, release PS and expose AuP s due to the reversible host-guest interaction at pH = 5.4, where photodynamic therapy and catalytic therapy were sufficiently activated to combat against the in-depth tumor. In vitro results indicate that the singlet oxygen yield of supramolecular AuP-PS nanoplatform was amplified 5.6 times under pH = 5.4 than that under pH = 7.4, and the nanozyme activity of AuP-PS nanoplatform was dramatically boosted 6.7 times than that of the control sample without reversible linkers under pH = 5.4. In vivo data further reveal that the supramolecular AuP-PS nanoplatform displayed superb therapeutic efficacy. Hence, this supramolecular AuP-PS nanoplatform may provide a programmed and complementary synergistic therapy strategy for in-depth and efficient treatment for solid tumors.

研究领域: 生物化学 · 纳米医学 · 肿瘤学
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RSC Advances · 2022 ·Vol. 12 ·期 54 ·34815-34821 · IF 4.036

Facile synthesis of phycocyanin/polydopamine hierarchical nanocomposites for synergizing PTT/PDT against cancer

Huazhen Liang,Yaling Sun,Chaoming Li,Huaming Lin,Qiwen Huang,Changguo Li

The exceptional biocompatibility and biosafety of natural proteins have made them a popular choice for tumor therapy in recent years, but their therapeutic effectiveness is severely constrained by factors including physiological instability, insufficient delivery, limited accumulation in tumor cells, etc. Here, a novel Mn-doped phycocyanin (Pc)/polydopamine (PDA) hierarchical nanostructure (MnPc@P) with excellent optical absorption, photothermal conversion, and photodynamic performances, is first designed and fabricated by a simply one-pot reaction, which not only successfully encapsulates natural protein Pc with intact activity in the nanostructure of MnPc@P but also gives them better biocompatibility. Upon laser irradiation, PDA-mediated hyperthermia and Pc-induced ROS elevation in tumor cells have been demonstrated, leading to drastic tumor cell death via combined PTT/PDT effect, greater than single PTT or PDT. In general, the expert fusion of Pc and PDA into a single nanomedicine opens fascinating perspectives in the delivery of natural proteins and tumor therapy.

研究领域: 生物材料 · 纳米医学 · 癌症研究
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