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Advanced Therapeutics · 2022 ·Vol. 5 ·期 12 ·2200108 · IF 5.003

Oxygen-Generated Hierarchical-Structured AuNRs@MnO2@SiO2 Nanocarrier for Enhanced NIR- and H2O2-Responsive Mild-Hyperthermia Photodynamic/Photothermal Combined Tumor Therapy

Wen-Jie Zheng,Ze-Lei Zhou,Qi-Yan Lv,Xiaojie Song,Wen-Xing Zhang,Hui-Fang Cui

Tumor hypoxia greatly restricts photodynamic therapy (PDT) efficiency. Photothermal therapy (PTT) implemented at high temperatures induces local skin burning and surrounding tissue damage. Herein, an near-infrared (NIR)- and H 2 O 2 -double responsive heat- and O 2 -generating core–shell–shell AuNRs@MnO 2 @SiO 2 nanocarrier with Au nanorods (AuNRs) as core and MnO 2 as sandwiched nanolayer is developed to realize enhanced photodynamic/photothermal combined tumor therapy at mild-hyperthermia temperatures. Coating poly- l -lysine on AuNRs is capable of preventing AuNRs from aggregation and facilitating the on-site growth of MnO 2 . The mesoporous SiO 2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO 2 nanolayer greatly enhances the singlet oxygen ( 1 O 2 ) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O 2 -enhanced PDT endows the AuNRs@MnO 2 @SiO 2 -ICG nanoparticles (NPs) dramatically stronger antitumor effect both in vitro and in vivo. Their tumor growth inhibition ratio (67.6%) is significantly higher than that of AuNRs@SiO 2 -ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO 2 @SiO 2 -ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO 2 @SiO 2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.

CAS / MDL: 57-09-0
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 药学
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ACS Applied Bio Materials · 2023 · IF 4.7

Physical Dissolution Combined with Photodynamic Depletion: A Two-Pronged Nanoapproach for Deoxygenation-Driven and Hypoxia-Activated Prodrug Therapy

Jingsong Lu,Jing Yu,Wensheng Xie,Xiaohan Gao,Zhenhu Guo,Zeping Jin,Ying Li,Abdul Fahad,Neema Ufurahi Pambe,Shenglei Che,Yen Wei,Lingyun Zhao

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
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Small · 2024 · IF 13

NIR-Triggered Multifunctional NO Nanoplatform for Conquering Thermal Resistance in Biofilms

Bingshuai Zhou,Biao Dong,Songtao Hu,Wei Liu,Liheng Sun,Lin Xu,Xue Bai,Lin Wang,Manlin Qi,Hongwei Song

Photothermal treatment (PTT) has emerged as a promising avenue for biofilm elimination, yet its potential drawbacks, such as local hyperpyrexia and bacterial heat resistance, have posed challenges. To address these concerns, an innovative nanoplatform (Au@mSiO 2 -arg/ICG) is devised that integrates phototherapeutic and gas therapeutic functionalities. This multifaceted nanoplatform is composed of mesoporous silica-coated Au nanorods (Au@mSiO 2 ), supplemented with l -arginine ( l -arg) and indocyanine green (ICG), and is engineered for mild temperature PTT aimed at biofilm eradication. Au@mSiO 2 -arg/ICG nanoparticles (NPs) show excellent antibacterial effects through the generation of nitric oxide (NO) gas, heat, and reactive oxygen species (ROS) under 808 nm light irradiation. The ROS generated by ICG initiates a cascade reaction with l -arg, ultimately yielding NO gas molecules. This localized release of NO not only effectively curbs the expression of heat shock proteins 70 mitigating bacterial thermoresistance, but also reduces extracellular polymeric substance allowing better penetration of the therapeutic agents. Furthermore, this nanoplatform achieves an outstanding biofilm elimination rate of over 99% in an abscess model under 808 nm light irradiation (0.8 W·cm −2 ), thereby establishing its potential as a dependable strategy for NO-enhanced mild PTT and antibacterial photodynamic therapy (aPDT) in clinical settings.

CAS / MDL: 5471-63-6 7761-88-8
研究领域: 纳米技术 · 生物医学工程 · 药学 · 微生物学 · 治疗学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

pH-Activated Scallop-Type Nanoenzymes for Oxidative Stress Amplification and Photothermal Enhancement of Antibacterial and Antibiofilm Effect

Yuping Jiang,Jiaman Xu,Quan Lin,Junyao Song,Maokun Sheng,Jintae Lee,Jinsheng Shi,Xiaoying Kong,Yulong Tan

Ferric phosphate (FePOs) nanoenzymes can express peroxidase (POD) activity under the dual stimulation of an acidic environment and high H2O2 concentrations. In living organisms, this generates reactive oxygen species (ROS) in sites of lesion infection, and thus FePOs nanoenzymes can act as antimicrobial agents. Here, CeO2 and ZnO2 were immobilized in a scallop-type FePOs nanoenzyme material loaded with a photosensitizer, indocyanine green, to synthesize a multifunctional cascade nanoparticle system (FePOs–CeO2–ZnO2–ICG, FCZI NPs). H2O2 concentrations could be adjusted through the ZnO2 self-activation response to the slightly acidic environment in biofilms, further promoting the release of ROS from the POD-like reaction of FePOs, achieving amplification of oxidative stress, DNA and cell membrane damage, and exploiting the photodynamic/photothermal effects of indocyanine green to enhance the antibiofilm effects. CeO2 can remove redundant ROS by switching from Ce4+ to Ce3+ valence, enhancing its ability to fight chronic inflammation and oxidative stress and thus promoting the regeneration of tissues around infection. By maintaining the redox balance of normal cells, increasing ROS at the infection site, eliminating redundant ROS, and protecting normal tissues from damage, the synthesized system maximizes the elimination of biofilms and treatment at the infection site. Therefore, this work may pave the way for the application of biocompatible nanoenzymes.

CAS / MDL: 557-34-6 5970-45-6
研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 药学 · 微生物学 · 生物化学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Self-enhanced ROS generation by responsive co-delivery of H2O2 and O2 based on a versatile composite biomaterial for hypoxia-irrelevant multimodal antibiofilm therapy

Jiayu Xiao,Luo Hai,Ke Yang,Yuze Luo,Zefeng Wang,Junqin Li,Chunlei Ou,Li Wang,Le Deng,Dinggeng He

Reactive oxygen species (ROS) such as hydroxyl radicals ( OH) and singlet oxygen ( 1 O 2 ) have emerged as promising therapeutic agents for combating biofilm-associated bacterial infections. However, the hypoxic microenvironments in the biofilms severely hinder the ROS production. Herein, we have rationally integrated copper peroxide (CP) and indocyanine green (ICG) into a polydopamine (PDA) nanoparticle to construct a versatile hybrid nanoplatform (PDA/CP/ICG), which can enhance ROS generation for highly efficient biofilm elimination by relieving hypoxic microenvironment. When the PDA/CP/ICG accumulates at the infection site or biofilm, the acidic microenvironment triggers the co-release of Cu 2+ and H 2 O 2 , and the former can catalyze the conversion of self-supplied H 2 O 2 into OH via a Fenton-like reaction and consume the overexpressed antioxidant glutathione (GSH) to further promote the oxidative stress. Moreover, with the help of an 808 nm laser, the hyperpyrexia caused by PDA induces the decomposition of CP into O 2 that is immediately converted by ICG into 1 O 2 . The PDA/CP/ICG shows satisfactory antibacterial and antibiofilm effect due to the self-amplified production of OH and 1 O 2 , and outstanding wound healing with good in vivo biosafety. Overall, this study provides a facile paradigm in ROS-based biofilm elimination, and the proposed hypoxia-irrelevant bactericidal nanoplatform has great potential for future biomedical applications.

研究领域: 生物材料 · 纳米医学 · 抗菌治疗 · 生物膜消除 · 伤口愈合
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Engineered Nanovesicles for the Precise and Noninvasive Treatment of Deep Osteomyelitis Caused by MRSA Infection with Enhanced Immune Response

Xingyue Yang,Ren Fang,Xiaotian Li,Weihao Kong,Yubao Jin,Ruohan Jiao,Zhenggong Liu,Meiqi Zhang,Qixian Peng,Yumiao Zhang,Ningning Song

The clinical treatment of hospital-acquired persistent osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) presents two major challenges: ineffective drug delivery into deep tissues and counteracting the rapid establishment of an immunosuppressive microenvironment. Indeed, MRSA can evade immunosurveillance and undermine both innate and adaptive immune responses. Herein, the engineered nanovesicles, functioning by combining sonodynamic therapy (SDT) with immune modulation, were constructed for the precise and noninvasive removal of MRSA in deep tissue and activation of the antimicrobial immune response using a newly engineered nanovesicle. Macrophage-derived M1 phenotypic microvesicles (M1-MW) internalized vancomycin-cross-linked micelles with the acoustic sensitizer indocyanine green (ICG) (VCG micelles). The vesicles of M1-MW were grafted with PEGylated mannose, allowing for targeted accumulation at the infection site. The VCG micelles were responsive to the highly reducing environment and released ICG to generate ROS after exposure to ultrasounds. This effect was combined with the presence of vancomycin to kill MRSA. In an osteomyelitis infection model, we observed an improved survival rate and reprogramming of macrophages to a pro-inflammatory M1 phenotype. The latter promoted T-cell activation and immune defense against MRSA-camouflaged homologous cell-transferred infections. Thus, our study presents a noninvasive and efficient treatment (VCG@MMW) for deep osteomyelitis with improved bacterial clearance and reduced risk of recurrence with enhanced immune response.

CAS / MDL: 1404-90-6
研究领域: 纳米技术 · 传染病学 · 免疫学 · 药学 · 生物医学工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2024 · IF 9.4

Amino acid-based metallo-supramolecular nanoassemblies capable of regulating cellular redox homeostasis for tumoricidal chemo-/photo-/catalytic combination therapy

Li Tu,Shengqiang Chen,Zhikang Yuan,Yeqi Xiong,Bingkun Luo,Ying Chen,Zhenqing Hou,Sunkui Ke,Naibo Lin,Chao Li,Shefang Ye

Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt 4+ -driven coordination co-assembly of l -cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.

CAS / MDL: 3317-61-1
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学
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Biomaterials Science · 2023 · IF 6.6

A biocompatible nano-barium sulfonate system for quad-modal imaging-guided photothermal radiotherapy of tumors

Yunfei Lian,Fenyan Feng,Xinwang Meng,Yue Hu,Meirong Huo,Guangji Wang,Juan Li

Integration of multi-modal imaging techniques and various cancer treatments based on their respective characteristics would be beneficial for enhancing anticancer efficacy. Exploiting an “all-in-one” nanoparticle with high biocompatibility has attracted widespread attention. Herein, two clinically proven modalities, human serum albumin (HSA) and indocyanine green (ICG), were selected to create HSA-stable barium sulfonate nanoparticles (HSA@ICG–Ba) through the reaction of a sulfonic acid group with barium ions. Our nano-probe showed excellent optical properties and X-ray absorption capacity, which can be applied in tumor theranostics. Utilizing the rich tumor accumulation of HSA@ICG–Ba, this nanoparticle can obtain multifaceted tumor information through fluorescence (FL), computerized tomography (CT), photoacoustic (PA) imaging, and single photon emission computed tomography (SPECT) imaging. Additionally, radiation sensitization therapy and photothermal therapy based on HSA@ICG–Ba were evaluated using both in vitro and in vivo models. The efficacy of tumor radiotherapy can be further improved by mild hyperthermia owing to the relieved tumor hypoxia. Finally, the favorable safety profile of HSA@ICG–Ba is confirmed by blood index analysis and tissue section observation. Therefore, this study explored an “all-in-one” barium sulfonate nanoparticle with high biocompatibility for FL/CT/PA/SPECT imaging-guided synergetic photothermal-radiotherapy of tumors, providing a new approach and potential pathway for tumor theranostics.

CAS / MDL: 10326-27-9
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 医学成像
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Nano Today · 2024 · IF 13.2

T lymphocyte-derived immunogenic hybrid nanovesicles for immunosuppression reversion and boosted photothermal immunotherapy

Jingyi Liu,Qing You,Siyuan Ye,JinJin Wang,Rong Du,Fuming Liang,Zhaohui He,Chen Wang,Ling Zhu,Yanlian Yang

Photothermal therapy (PTT) can mediate the immunogenic cell death (ICD) of tumors through photothermal transformation, thus releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) to stimulate the maturation of dendritic cells (DCs) and elicit the immune response against tumors. However, PTT-mediated upregulation of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) will cause the immune evasion of tumor cells and thus increases the immunosuppression of cytotoxic T lymphocytes (CTLs), resulting in restricted photothermal immune activation. Taking advantage of the high expression of programmed cell death protein 1 (PD-1) in T lymphocytes, we develop an immunogenic photothermal hybrid nanovesicle to reverse immunosuppression and enhance PTT-induced ICD. The hybrid vesicle (TMVL-I) is constructed by phospholipid bilayer fusion of T cell-derived membrane vesicle (TMV) with high PD-1 expression and the indocyanine green (ICG)-loaded thermosensitive liposome (L-I). TMVL-Is bind to the tumor cells with PTT-induced upregulation of PD-L1, effectively blocking the PD-1/PD-L1 pathway between CTLs and tumor cells, thus reversing PD-L1-mediated tumor immunosuppression and intensifying photothermal-induced ICD effects. These processes significantly induce the maturation of DCs and enhance the infiltration of CTLs into both primary and distal tumors and the activation of spleen CTLs, strongly inhibiting the growth of B16 xenograft tumors and greatly improving the survival rate of B16 xenograft mice. This work provides a feasible strategy for immunosuppressive microenvironment reprogramming-based combination therapy.

CAS / MDL: 178119-00-1
研究领域: 癌症治疗 · 纳米技术 · 免疫学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2019 · IF 8.355

A synergistic cancer immunotherapy nano-system for preventing tumor growth

Yingying Zhang,Hongbin Chen,Hanjie Wang,Tiange Wang,Huizhuo Pan,Wanying Ji,Jin Chang

Immunotherapy has become a promising therapy in cancer treatment. Both photothermal therapy (PTT) and genotoxic chemotherapy can trigger immune responses. On this subject, a synergistic cancer immunotherapy nano-system was developed for treating primary and distant tumors. This long-time, synergistic therapeutic system consisted of two parts: one was indocyanine green (ICG) and sepantronium bromide (YM155) co-loaded mesoporous silica nanoparticles (MSNs) for PTT and genotoxic chemotherapy, which could effectively destroy primary tumors and thus cause exposure of tumor antigens for cancer immunotherapy. The other was silica nanoparticles (nSiO 2 ) coated with magnetic nanoparticles (MNP) and conjugated with anti-CD47 antibody (anti-CD47), which demonstrated a strong antitumor immune effect of distant tumors after PTT and genotoxic chemotherapy. In vitro and vivo results proved that this synergistic system could efficiently inhibit primary and distant tumor growth. We expected that this paper may develop a promising strategy to prevent tumor growth for basic and clinical research.

CAS / MDL: 111-42-2 78-10-4
研究领域: 癌症治疗 · 纳米技术 · 免疫学 · 药理学
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Science Advances · 2020 ·Vol. 6 ·期 36 · IF 13.117

A tumor-to-lymph procedure navigated versatile gel system for combinatorial therapy against tumor recurrence and metastasis

Lin Qin,Jun Cao,Kun Shao,Fan Tong,Zhihang Yang,Ting Lei,Yazhen Wang,Chuan Hu,Channakeshava Sokke Umeshappa,Huile Gao,Nicholas A. Peppas

Application of cancer vaccines is limited due to their systemic immunotoxicity and inability to satisfy all the steps, including loading of tumor antigens, draining of antigens to lymph nodes (LNs), internalization of antigens by dendritic cells (DCs), DC maturation, and cross-presentation of antigens for T cell activation. Here, we present a combinatorial therapy, based on a α-cyclodextrin (CD)–based gel system, DOX/ICG/CpG-P-ss-M/CD, fabricated by encapsulating doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon irradiation, the gel system exhibited heat-responsive release of DOX and vaccine-like nanoparticles, CpG-P-ss-M, along with chemotherapy- and phototherapy-generated abundant tumor-specific antigen storage in situ. The released CpG-P-ss-M acted as a carrier adsorbed and delivered antigens to LNs, promoting the uptake of antigens by DCs and DC maturation. Notably, combined with PD-L1 blocking, the therapy effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis.

研究领域: 肿瘤学 · 免疫治疗 · 药学 · 生物医学工程
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JOURNAL OF RARE EARTHS · 2025 · IF 7.2

Dye-sensitized rare-earth-doped nanoparticles and MOF heterostructures for enhanced NIR-II fluorescence imaging and synergistic photothermal and photodynamic therapy

Ming Qian,Jiarui Du,Qichuan Jiang,Wei Tao,Jiayi Zhang,Liang Gong

Early diagnosis and treatment of cancer are key problems for effective cancer therapy. Therefore, the development of multifunctional materials that can integrate imaging and therapeutic functions is of great importance. Lanthanide-doped nanoparticles@metal-organic frameworks (Ln-NPs@MOFs) offer an unprecedented opportunity to address this challenge, by combining the imaging capabilities of rare earth-doped nanoparticles with the photosensitizing properties of MOFs for photodynamic therapy (PDT). Here, we report a near-infrared (NIR) light-responsive nanoparticle based on a zirconium-porphyrin metal-organic framework (PCN-224) for synergistic photothermal and photodynamic therapy. Tetra(4-carboxyphenyl)porphyrin (TCPP) that constitutes the MOF framework serves as a natural photosensitizer, enabling efficient photodynamic therapy through Förster resonance energy transfer (FRET). The dye indocyanine green (ICG) was loaded into the MOF pores to sensitize the Ln nanoparticles, enhancing the upconversion fluorescence by 41 times and the downconversion fluorescence by 5 times, which is beneficial to the biological efficacy for imaging diagnosis. Meanwhile, ICG, a traditional photothermal agent, also imparts photothermal therapy capabilities to the system. Furthermore, the encapsulation of cancer cell membranes not only enhances biocompatibility but also improves the material's targeting towards cancer cells, thereby greatly enhancing the therapeutic effect. This dual-functional material provides a promising platform for the integration of cancer diagnosis and therapy.

研究领域: 生物医学工程 · 纳米医学 · 癌症诊疗一体化 · 光学成像 · 光疗
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