Small
·
2021
·Vol. 17
·期 10
·2007953
·
IF 13.281
Cheng Wang,Shaoqing Chen,Fangying Yu,Jianghong Lv,Rui Zhao,Fuqiang Hu,Hong Yuan
A conventional theranostic system usually employs a single fluorescence channel to show the pharmacokinetic events, which usually fails to quantitatively reveal the true cumulative drug release and with low accuracy. Herein, indocyanine green (ICG) and chlorins e6 (Ce6) are selected not only as conventional photothermal/photodynamic agents, but also to offer two independent fluorescence channels to cross validate the authenticity of pharmacokinetic events and to quantitatively reveal cumulative drug release in tumor tissues in a “turn on” manner. Employing the Ca 2+ of amorphous calcium carbonate as a reversible linker, the photosensitivity and fluorescence of Ce6 are physically quenched by ICG during circulation to reduce the side effect of photodynamic therapy (PDT) while being readily restored in tumor tissue to reveal the quantitative drug release. Most importantly, the combination of photothermal therapy (PTT) and PDT allows low-temperature synergistic therapy of cancer through the controlled expression of heat shock protein in cells and mild hyperthermia enhanced reactive oxygen species diffusion/penetration among cells. This work not only develops a facile approach to fabricate a dual-channel theranostic system to precisely indicate the accumulation and quantitative drug release in tumor tissue, but also presents a unique low-temperature synergistic strategy to destroy tumor in an effective and minimally invasive manner.
研究领域:
癌症治疗
·
生物医学工程
·
药学
·
纳米技术
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 9
·2370-2383
·
IF 7.59
Lu Tang,Qiaqia Xiao,Yue Yin,Yijun Mei,Jing Li,Lin Xu,Hongbin Gao,Wei Wang
A combination of photothermal therapy (PTT) and chemotherapy is an emerging therapeutic strategy with promising clinical prospects in cancer treatment. Despite the huge progress achieved in the past years, a number of obstacles still hamper the therapeutic efficacy of this synergistic modality such as uneven heat distribution, lack of targetability of anti-cancer agents and dosage-related side effects. Thus, developing a nanoplatform for targeted drug delivery against cancer is of great necessity. Herein, a lipid–polymer hybrid nanosystem (LP/ID) based on polyethyleneimine (PEI)-lecithin-polyethylene glycol (PEG) was fabricated to co-load indocyanine green (ICG) and dichloroacetate (DCA) for combined photothermal/chemotherapy. DCA and ICG were linked to the PEI backbone to form a dense hydrophobic core through amide bonds and electrostatic interactions, which increased the payload of DCA and ICG as well as achieved enzyme-responsive drug release because of the overexpressed amidase in tumor cells. Lecithin and DSPE-PEG2000 self-assembled around the hydrophobic complexes to obtain prolonged blood circulation and attenuated systemic toxicity of the hybrid nanosystem. The prepared LP/ID exhibited favourable stability in a physiological environment, good tumor imaging properties, and satisfactory photothermal/chemotherapeutic performance. Moreover, LP/ID could also enhance the cellular uptake and tumor retention capacity in comparison with free drug administration. Notably, by co-loading two therapeutic agents with different anti-cancer mechanisms, an obvious inhibitory effect on tumor growth was observed with negligible damage to normal tissues and organs because of the synergistic photothermal/chemotherapy effect, indicating the great potential of LP/ID as a robust nanoplatform for cancer treatment.
研究领域:
癌症治疗
·
纳米医学
·
材料科学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Junqin Li,Mengya Sun,Xiaoxian Tang,Yuqian Liu,Chunlei Ou,Yuze Luo,Li Wang,Luo Hai,Le Deng,Dinggeng He
Reactive oxygen species (ROS) are widely considered to the effective therapeutics for fighting bacterial infections especially those associated with biofilm. However, biofilm microenvironments including hypoxia, limited H 2 O 2 , and high glutathione (GSH) level seriously limit the therapeutic efficacy of ROS-based strategies. Herein, we have developed an acidic biofilm microenvironment-responsive antibacterial nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The three-in-one nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in a slightly acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into hydroxyl radical (•OH) and consumes the highly expressed GSH to disrupt the redox homeostasis. With the assistance of an 808 nm laser, the loaded ICG not only triggers the production of singlet oxygen ( 1 O 2 ) by a photodynamic process, but also provides photonic hyperpyrexia that further promotes the Fenton-like reaction for enhancing •OH production and induces thermal decomposition of CuO 2 for the O 2 -self-supplying 1 O 2 generation. The CuO 2 /ICG@CBSA with laser irradiation demonstrates photothermal-augmented multi-mode synergistic bactericidal effect and is capable of inhibiting biofilm formation and eradicating the biofilm bacteria. Further in vivo experiments suggest that the CuO 2 /ICG@CBSA can effectively eliminate wound infections and accelerate wound healing. The proposed three-in-one nanotherapeutics with O 2 /H 2 O 2 -self-supplied ROS generating capability show great potential in treating biofilm-associated bacterial infections. Statement of Significance Here, we have developed an acidic biofilm microenvironment-responsive nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in an acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into •OH and consumes the overexpressed GSH to improve oxidative stress. With the aid of an 808 nm laser, ICG provides photonic hyperpyrexia for enhancing •OH production, and triggers O 2 -self-supplying 1 O 2 generation. CuO 2 /ICG@CBSA with laser irradiation displays photothermal-augmented multi-mode antibacterial and antibiofilm effect. Further in vivo experiments prove that CuO 2 /ICG@CBSA effectively eliminates wound infection and accelerates wound healing. The proposed three-in-one nanotherapeutics show great potential in treating biofilm-associated bacterial infections.
研究领域:
纳米技术
·
生物材料
·
生物医学工程
·
微生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 15
·1900192
·
IF 6.27
Tianliang Li,Jia Zhou,Lirui Wang,Hanfu Zhang,Cunfeng Song,Jesús M. de la Fuente,Yunxiang Pan,Jie Song,Chunlei Zhang,Daxiang Cui
Emerging Fenton-like activity of copper ions has inspired great exploration for tumor microenvironment-activated tumor therapy due to the toxic ·OH production for chemodynamic therapy and extra oxygen generation for photodynamic therapy (PDT). Still, the ·OH produced by copper ions is not satisfied even when copper ions are placed in a low pH environment (pH ≈ 5.0). To amplify its Fenton-like activity, in this work, one kind of Cu 2+ –protein self-assemblies (C-m-ABs) loaded with photosensitizer indocyanine green (ICG) is constructed, which can catalyze H 2 O 2 generating more amounts of ·OH under light irradiation once Cu 2+ is reduced to Cu + by glutathione. Such fantastic phenomena confirms that C-m-ABs can act as a photo-Fenton-like agent. Furthermore, C-m-ABs can dramatically accelerate O 2 generation (catalase activity) to enhance the PDT of ICG. After loading with the anticancer drug doxorubicin, C-m-ABs are further self-assembled into novel nanobelts, which simultaneously exhibit superior photo-heat conversion effects, enhanced r1 relaxation (21.416 s −1 m m −1 ) and stimuli-responsive drug release behaviors. High cytotoxicity in vitro, effective tumor accumulation capacity observed by fluorescence/photoacoustic/magnetic resonance imaging, and enhanced chemo-/photodynamic/photothermal therapeutic performance are achieved. Based on these results, a photo-Fenton-like metal–protein self-assemblies demonstrate great potential for tumor theranostics.
研究领域:
癌症治疗
·
纳米医学
·
生物医学工程
·
材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yufei Liu,Yao Qi,Chen Chen,Yincheng Jin,Shi Du,Jianan Qiao,Jing Yao
Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus ( S. aureus ) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.
研究领域:
癌症生物学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Ming Qian,Lei Song,Zefan Huang,Xiucheng Hu,Yunpeng Bai,Yukun Chen,Na An,Haipeng Sun
Bacterial antibiotic resistance poses a global threat to public health, highlighting the urgent need for innovative antimicrobial strategies. Zinc-based nanomaterials have shown promise in antibacterial treatments but are often limited by their low antimicrobial efficiency and poor biocompatibility. In this study, we propose a synergistic antibacterial approach that utilizes the Trojan horse effect through nanocomposites. By exploiting bacterial dependence on Fe3+, we introduce Ga3+ as a substitute, disrupting bacterial growth from within. Utilizing a ZIF-L carrier to load indocyanine green (ICG), we achieve targeted delivery of ICG, which generates ROS under light irradiation, effectively eradicating methicillin-resistant Staphylococcus aureus biofilms. In addition, the combined application of Zn2+ and Ga3+ effectively inhibits the growth of Porphyromonas gingivalis, providing complementary synergistic damage to bacteria from the inside out. This combined approach, integrating Zn2+, the Trojan horse mechanism, and photodynamic therapy, offers a promising therapeutic strategy against bacterial antibiotic resistance.
研究领域:
纳米技术
·
抗菌治疗
·
光动力疗法
·
材料科学
·
生物医学工程
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Xin Wan,Ying Zhang,Yiqun Wan,Mengmeng Xiong,Anqi Xie,Yongye Liang,Hao Wan
The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3–ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3–ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL’s direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe3O4@PDA@CaCO3–ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3–ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Xiudan Wang,Yuling Mao,Changshan Sun,Qinfu Zhao,Yikun Gao,Siling Wang
Excellent efficiency of combinational therapy of chemotherapy and photodynamic therapy (PDT) highly depends on the amounts of drug and oxygen in tumor tissue. However, how to cleverly promote drug release accompanied with improving oxygen concentration remains a challenge. Herein, we proposed a gas-generator that realized a high drug loading and integrated facilitation of drug release with oxygen replenishment into a single and simple system, utilizing huge cavities and mesoporous channels of hollow mesoporous silica nanoparticles (HMSNs) for encapsulating oxygen (O 2 ) saturated perfluoropentane (PFP) droplets, indocyanine green (ICG) and doxorubicin (DOX), biocompatible polydopamine (PDA) as the gatekeepers. Under irradiation of 808 nm laser , the thermal effect of PDA caused PFP droplets occur liquid-gas phase transition that triggered the burst release of DOX and O 2 , finally amplifying the synergetic effects of PDT and chemotherapy both in vitro and in vivo. The influence of PFP, GSH and laser on drug release kinetic was explored through mathematical models. Notably, the mechanism of gas-generator on accelerating drug release under irradiation based on doing volume work and enhancing diffusion coefficient was clarified by researching the relation between DOX release, PFP release and temperature change. Additionally, the way of replenishing O 2 did not rely on intracellular components but timely offered abundant “fuels” for producing reactive oxygen species (ROS) when compared with traditional manners. This work provides a new research strategy for boosting drug release and opens an avenue for constructing multifunctional controlled delivery systems.
研究领域:
癌症治疗
·
纳米医学
·
药物递送系统
·
光动力疗法
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Qi Sun,Zhenzhen Yang,Meng Lin,Yiwei Peng,Rudong Wang,Yitian Du,Yu Zhou,Jiajia Li,Xianrong Qi
Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment . Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem , [email protected] , is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles . The [email protected] exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3 + regulatory T cells (4.3-fold) and increase of CD4 + effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of [email protected] is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2016
·Vol. 12
·期 31
·4286-4298
·
IF 8.315
Qi Lei,Wen-Xiu Qiu,Jing-Jing Hu,Peng-Xi Cao,Cheng-Hui Zhu,Han Cheng,Xian-Zheng Zhang
In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2022
·Vol. 5
·期 12
·2200108
·
IF 5.003
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.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 13
·2937-2945
·
IF 7
Lanfang Zhang,Hui Lu,Yu Tang,Xiaojie Lu,Zhendong Zhang,Yan Zhang,Ying Liu,Chenhui Wang
Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子