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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2022 · IF 3.682

Preparation, stimuli-response performance of HPC-PMAA/PpIX nanogels and their application in photodynamic therapy

Chengyan Zhao,Qiusheng Song,Lin Zhu,Haihong Ma

In the present study, a novel nanogel of HPC-PMAA/PpIX with thermo- and pH sensitive performance and its application in cancer photodynamic therapy is reported. HPC-PMAA/PpIX nanogels were prepared by free radical polymerization method with HPC as template, hydroxypropyl cellulose (HPC), methyl acrylic acid (MAA), protoporphyrin IX (PpIX) and N,N′-methylene bisacrylamide (BIS) as raw materials. The as-prepared nanogels were characterized by Fourier transform infrared (FTIR), photoluminescence (PL) and UV–visible spectrophotometer (UV–vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). PL and UV–vis spectra demonstrate that PpIX is incorporated into HPC-PMAA by covalent bonds, and its aggregation is prevented. Moreover, the as-prepared nanogels can be dispersed in water over 1 week, significant singlet oxygen can be produced under irradiation of laser. With tumor cell of HepG2 as model cell, the nanogels are biocompatible with cell viability of >85% even at high concentrations of the PpIX in vitro. In addition, the HPC-PMAA/PpIX nanogels show photo-dependent toxicity in the concentration range of 10 µg/mL of PpIX, suggesting that HPC-PMAA/PpIX nanogels have potential for the treatment of photodynamic therapy (PDT).

研究领域: 生物医学工程 · 癌症治疗 · 材料科学
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ACS Omega · 2024 · IF 3.7

Preparation of MPN@Zein-PpIX Membrane and Its Antibacterial Properties

Wenhong Zhou,Zhonghao Jiang,Xiao Lin,Yanan Chen,Quanxin Wu,Jia Chen,Feng Zhang,Guolie Xie,Yang Zhang,Jiantao Lin,Ning Guo

For antibacterial purposes, a photothermal and photodynamic antibacterial membrane was prepared through electrospinning. We used zein as the substrate and introduced Protoporphyrin IX (PpIX) into the protein structure. Then, we used electrospinning technology to weave the modified zein into a fiber structure. We finally introduced a metallic polyphenol network (MPN) coating on the fiber surface to form the final membrane: MPN@Zein-PpIX. Then, we investigated the photothermal and photodynamic properties of the membrane and assessed its antibacterial activity with in vitro agar plate counting methods. The MPN@Zein-PpIX membrane exhibited good singlet oxygen generation and excellent photothermal conversion. Additionally, it showed good antibacterial capacity in vitro, owing to the combination of photothermal and photodynamic properties. Our research provides a simple approach to prepare a multifunctional membrane with excellent antibacterial ability. We used the electrospinning technique to anchor PpIX onto zein to produce a fiber membrane (Zein-PpIX) that can be adhered in situ to improve the biocompatibility of PpIX, and the MPN makes the membrane surface more hydrophilic and more accessible to adhere to biological tissues. The MPN@Zein-PpIX membrane provided new ideas for combining PDT and PTT, and it had great potential for use in the antibacterial application field.

研究领域: 材料科学 · 生物医学工程 · 纳米技术 · 抗菌技术
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2023 · IF 5

Phenylboronic acid-functionalized BSA@CuS@PpIX nanoparticles for enhanced antibacterial photodynamic/photothermal therapy

Yun Liu,Qian Lan,Jinxiu Liu,Yaxin Shi,Quanxin Wu,Qian Wang,Shuang Yang,Fan Cheng

To avoid the occurrence of antibiotic resistance and improve bactericidal effect, a multifunctional antibacterial nanoagent BCPP was successfully constructed for targeted photodynamic/photothermal combination therapy (PDT/PTT). The prepared BCPP consists of protoporphyrin (PpIX) as the photosensitizer , CuS nanoparticles as the photothermal agent, phenylboric acid (PBA) as the bacteria-targeting segment and bovine serum albumin (BSA) as the colloid stabilizer. Afterwards, its photodynamic/photothermal capacities, bacteria-targeting effect and bactericidal efficiency were intensively investigated. Experimental results confirmed its good singlet oxygen generation ability and high photothermal conversion efficiency. In addition, BCPP displayed good bacteria-targeting properties for both S. aureus and E. coli . Moreover, in vitro antibacterial assays proved its enhanced therapeutic efficiency through combined antibacterial PDT/PTT owing to PBA-mediated bacteria-targeting function. Finally, in vitro assays revealed its good hemocompatibility and low cytotoxicity. To sum up, our study offered a convenient method to build non-antibiotic antibacterial nanoagents for targeted PDT/PTT, and the prepared bactericidal is a promising drug candidate suitable for clinical trials in the future.

CAS / MDL: 553-12-8
研究领域: 纳米技术 · 光疗 · 抗菌剂 · 材料科学 · 生物医学工程
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JOURNAL OF PHYSICAL CHEMISTRY B · 2023 · IF 3.3

Experimental Verification of the Accuracy of Oxygen-Varying Correlated Fluorescence for Determining the Quenching Constant KSV

Lu Li,Meng Kou,Yongda Wang,Feng Qin,Hua Zhao,Zhiguo Zhang

The oxygen-varying correlated fluorescence provides an effective strategy to gain the quenching constant KSV for a non-phosphorescent system. Owing to the absence of detectable phosphorescence emission in general optical spectroscopy, the facticity of this method has never been verified. Here, the correct way to determine KSV by oxygen-varying correlated fluorescence was systematically studied in detail. We selected gadolinium protoporphyrin IX (Gd-PpIX) to establish a fluorescence and phosphorescence dual emission system. Then, KSV of Gd-PpIX can be obtained by the change of fluorescence intensity (IF) with oxygen concentration using the method of correlated fluorescence at intense pump power; meanwhile, the value can also be determined from the relationship of the phosphorescence intensity ratio and oxygen content by the Stern–Volmer equation under relatively low power density. It was found that the KSV values obtained by the above two methods were 12.2(1) and 11.9(7) kPa–1, respectively. Our results successfully verified the accuracy of oxygen-varying correlated fluorescence for determining the KSV by the phosphorescence property and fluorescence saturation of Gd-PpIX.

CAS / MDL: 553-12-8
研究领域: 生物化学 · 医学检测
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ACS Omega · 2022 · IF 4.132

PpIX/IR-820 Dual-Modal Therapeutic Agents for Enhanced PDT/PTT Synergistic Therapy in Cervical Cancer

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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Scientific Reports · 2026 · IF 4.9

Standardized acoustic characterization and temperature monitoring reveal platform-dependent outcomes in liposomal PpIX-mediated sonodynamic therapy

Yan Mengqi,Li Chen,Li Cuixian,Zhuang Fan,Zhu Piao,Huang Beijian

To compare sonodynamic therapy (SDT) efficacy mediated by protoporphyrin IX-loaded liposomes (PLP) and heating effects across three non-focused ultrasound (US) platforms under approximately matched geometric-area-normalized intensity ( I MGA ). Three platforms were evaluated using a standardized direct-contact 96-well 4T1-cell model. Acoustic power was measured using a radiation force balance, with I MGA derived from measured power and visible transducer-face area. Cell viability was assessed by CCK-8, intracellular reactive oxygen species (ROS) generation by DCFH-DA-based imaging and flow cytometry, and the heating effect by infrared thermography supplemented with thermocouple measurements. Despite matched I MGA , platforms differed in cytotoxicity and heating. At low I MGA , US-alone cytotoxicity was limited, whereas PLP-dependent viability loss was observed for Platforms A and B. At high I MGA , Platforms A and B showed US-alone cytotoxicity and spatial heterogeneity, whereas Platform C retained PLP-dependent cytotoxicity. PLP + US enhanced intracellular ROS generation across all three platforms. Endpoint temperature was inversely associated with US-alone cell viability at high I MGA for Platforms A and B. At a fixed displayed intensity, measured time-averaged acoustic power scaled approximately with duty cycle. PLP-mediated SDT efficacy remained platform-dependent at approximately matched I MGA . Independent verification of acoustic output and temperature monitoring are essential for reproducible cross-platform interpretation of SDT studies.

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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Ultrasound-Triggered on Demand Lidocaine Release Relieves Postoperative Pain

Chen Xiaohong,Zhang Jianfeng,Yu Yan,Wang Haoran,Ma Genshan,Wang Di,Cao Hanzhong,Yang Jianping

Safe and non-invasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and non-invasive controlled drug release. Here, we created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three-dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). It allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The Lido-PPIX@ER hydrogel under individualized ultrasound triggering released lidocaine and provided effective analgesia for more than 72 h. The withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group. The Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain. This article presents the delivery system for a new effective strategy to reduce pain, remotely control pain, and offer timed and spatiotemporally controlled release of Lido to manage postoperative pain.

CAS / MDL: 9001-62-1
研究领域: 药理学 · 生物医学工程 · 材料科学 · 麻醉学
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TALANTA · 2025 · IF 6.1

Colorimetry/fluorescence dual-signal sensing system based on peptide nanotubes activating hemin and PPIX for sensitive detection of tannic acid

Rong Tang,Chenglin Zhang,Baolian Liu,Yujie Kang,Ya Wang,Xiupei Yang

Recently, it has become valuable to develop strategies based on multi-mode sensors to detect analytes related to human health, food safety and environmental pollution. In this study, KL@PPIX-hemin composite prepared by immobilizing hemin and protoporphyrin IX (PPIX) on self-assembled peptide nanotubes (PNTs) through multiple non-covalent interactions were used for colorimetric/fluorescent dual-mode sensing of tannic acid (TA). PNTs as a carrier can provide the hydrophobic microenvironment for hemin and PPIX to protect them from dimerization, thus activating their respective peroxidase-mimicking activity and fluorescence emission. Further experiments show that the composite could catalyze H 2 O 2 to oxidize colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to generate blue ox-TMB, which could exactly quench the emission of PPIX by inner filter effect. The added TA can reduce ox-TMB to TMB and further turn on the fluorescence of system. A colorimetric/fluorescent dual-mode sensing system for TA was thus constructed and a low limit of detection (13.2 nM) was obtained. In addition, the analytical strategy has been successfully applied to accurate TA determination in actual tea samples. The method was also combined with smartphone to achieve visual detection of TA, which provides a broad prospect for portable and rapid tannic acid analysis.

研究领域: 分析化学 · 生物医学工程 · 食品安全检测
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Asian Journal of Pharmaceutical Sciences · 2022 · IF 9.273

pH-activatable oxidative stress amplifying dissolving microneedles for combined chemo-photodynamic therapy of melanoma

Yanjuan Huang,Hualu Lai,Jingwen Jiang,Xiaoyu Xu,Zishan Zeng,Lingling Ren,Qiuxing Liu,Meixu Chen,Tao Zhang,Xin Ding,Chunshun Zhao,Shengmiao Cui

Photodynamic therapy (PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation, but the strong hydrophobicity and poor tumor selectivity of photosensitizers, as well as the oxygen-consuming properties of PDT, leading to unsatisfactory therapeutic outcomes. Herein, a tumor acidic microenvironment activatable dissolving microneedle (DHA@HPFe-MN) was developed to realize controlled drug release and excellent chemo-photodynamic therapy of melanoma via oxidative stress amplification. The versatile DHA@HPFe-MN was fabricated by crosslinking a self-synthesized protoporphyrin (PpIX)-ADH-hyaluronic acid (HA) conjugate HA-ADH-PpIX with “iron reservoir” PA-Fe 3+ complex in the needle tip via acylhydrazone bond formation, and dihydroartemisinin (DHA) was concurrently loaded in the hydrogel network. HA-ADH-PpIX with improved water solubility averted undesired aggregation of PpIX to ensure enhanced PDT effect. DHA@HPFe-MN with sharp needle tip, efficient drug loading and excellent mechanical strength could efficiently inserted into skin and reach the melanoma sites, where the acidic pH triggered the degradation of microneedles, enabling Fe-activated and DHA-mediated oxidation treatment, as evidenced by abundant reactive oxygen species (ROS) generation. Moreover, under light irradiation, a combined chemo-photodynamic therapeutic effect was achieved with amplified ROS generation. Importantly, the Fe-catalyzed ROS production of DHA was oxygen-independent, which work in synergy with the oxygen-dependent PDT to effectively destroy tumor cells. This versatile microneedles with excellent biosafety and biodegradability can be customized as a promising localized drug delivery system for combined chemo-photodynamic therapy of melanoma.

研究领域: 肿瘤学 · 药剂学 · 生物医学工程
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ANALYTICAL CHEMISTRY · 2016 · IF 5.886

Functional Nucleic Acid Probe for Parallel Monitoring K+ and Protoporphyrin IX in Living Organisms

Hanjun Cheng,Xuefeng Qiu,Xiaozhi Zhao,Wei Meng,Da Huo,Hui Wei

Parallel monitoring of K+ and protoporphyrin IX (PPIX) is of vital importance because they are not only involved in a variety of biological processes but also closely linked to each other in numerous cellular pathways. However, there are currently no existing methods that can meet the requirements for parallel and in vivo detection of K+ and PPIX in living organisms. Herein, we demonstrated a functional nucleic acid (FNA)-based technique for parallel monitoring of K+ and PPIX in living animals. Specifically, the selected G-rich FNA probe was selectively induced to form a parallel G-quadruplex by K+. The parallel G-quadruplex then remarkably enhanced the fluorescence of PPIX. Thus, by modulating the fluorescence “turn on” with the G-quadruplex and K+/PPIX, both K+ and PPIX could be detected. After validating the developed method for selective and sensitive detection of K+ and PPIX in vitro, their dynamic changes in living organisms (i.e., living brains and tumors) following various physiological and pathological processes were simultaneously monitored. The current study not only provides a general method for the detection of metal ions and bioactive molecules but also presents a way to investigate their synergistic functions in the regulation of various biological processes. It may also be helpful for improving the imaging and therapeutic efficacy of PPIX and 5-ALA.

CAS / MDL: 5451-09-2
研究领域: 生物化学 · 分子生物学 · 生物医学工程 · 分析化学
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Frontiers in Chemistry · 2019 · IF 3.782

A Theranostic Nanoprobe for Hypoxia Imaging and Photodynamic Tumor Therapy

Fan Jing Hao,Fan Gui Ling,Yuan Ping,Deng Fu An,Liu Ling Shan,Zhou Xiang,Yu Xi Yong,Cheng Hong,Li Shi Ying

Hypoxia is a common feature for most malignant tumors, which was also closely related to the oxygen-dependent photodynamic therapy. Based on Förster resonance energy transfer (FRET), a smart nanoprobe (designated as H-Probe) was designed in this paper for hypoxia imaging and photodynamic tumor therapy. Due to the FRET process, H-Probe could respond to hypoxia with a significant fluorescence recovery. Moreover, abundant in vitro investigations demonstrated that the photosensitizer of PpIX in H-Probe could generate large amounts of singlet oxygen to kill cancer cells in the presence of oxygen and light with appropriate wavelength. Also, intravenously injected H-Probe with light irradiation achieved an effective tumor inhibition in vivo with a reduced side effect. This original strategy of integrating hypoxia imaging and tumor therapy in one nanoplatform would promote the development of theranostic nanoplatform for tumor precision therapy.

研究领域: 癌症研究 · 诊疗学 · 分子影像 · 纳米医学
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Journal of Materials Chemistry B · 2019 ·Vol. 7 ·期 7 ·1087-1095 · IF 5.047

A versatile bacterial membrane-binding chimeric peptide with enhanced photodynamic antimicrobial activity

Ai-Nv Zhang,Wei Wu,Chi Zhang,Qiu-Yang Wang,Ze-Nan Zhuang,Han Cheng,Xian-Zheng Zhang

Photodynamic therapy (PDT) has become an effective antibiosis method for overcoming antibiotic resistance. In this study, we developed a versatile bacterial membrane-binding chimeric peptide PpIX-[PEG8-(KLAKLAK)2]2 (denoted as PPK) by conjugating a photosensitizer protoporphyrin IX (PpIX) with an antimicrobial peptide (KLAKLAK)2 (KLA) for effective photodynamic inactivation of bacteria. The chimeric peptide PPK with positively charged properties and an α-helical conformation could rapidly bind to microbial cells through electrostatic interactions and membrane insertion. Moreover, PPK could disrupt the bacterial membrane and further elicit lipid bilayer leakage to kill bacteria by toxic reactive oxygen species (ROS) generated by PpIX under 660 nm light. In vitro experiments demonstrated that cationic PPK possessed excellent antimicrobial activity against both Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). Afterward, PPK also exhibited perfect therapeutic effects on S. aureus-infected mice without any systemic side effects. This chimeric peptide PPK will show great potential for photodynamic antibiosis.

研究领域: 微生物学 · 药剂学 · 分子生物学
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