JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Hao Tian,Zihan Huang,Xiangding Liu,Quan Zuo,Jiang Wu,Xueyao Chen,Xin Gao,Dengfu Wu,Xingkai Wang,Hongyi Huang,Shuo Jiang,Yuxin Song,Siqi Zhang,Feng Wang,Peng Liu,Rui Wang,Kuan Hu
Prostate cancer (PCa) remains highly prevalent and deadly, and its progression to castration resistance is still difficult to treat despite recent therapeutic advances. Peptide-drug conjugates (PDCs) have emerged as promising targeted therapeutics for cancer, yet their clinical translation is hindered by unsatisfactory in vivo performance and limited ability for reliable tracking. Here, we present PXC-4, a Gastrin Releasing Peptide Receptor (GRPR)-targeting multifunctional PDC based on GRPR antagonist JMV-594 and the cytotoxic payload monomethyl auristatin E (MMAE), for precise PCa therapy. PXC-4, by leveraging indocyanine green (ICG), acquired multifunctionality and optimized antitumor activity. Installing of ICG substantially increased cell penetration (6.25-fold at 4 h) and tumor accumulation (3.82-fold at 4 h) of PXC-4, resulting in 89% inhibition of prostate tumor growth via lysosome-mediated toxin release with markedly improved safety. Upon 808 nm laser irradiation, PXC-4 further achieved 99% tumor suppression through photodynamic therapy coupled with its cytotoxic payload. In addition, incorporation of DOTA enabled precise in vivo tracking via 64 Cu-PET imaging and facilitated multimodal synergistic tumor inhibition via 177 Lu-radionuclide therapy. Collectively, our findings suggest that rational ICG installation markedly elevates the functional competence of GRPR-targeting PDC, giving rise to an enhanced multifunctional therapeutic entity capable of diagnosis, image-guided surgery, and targeted treatment for PCa.
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Biomaterials Science
·
2023
·Vol. 11
·期 7
·2359-2371
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IF 6.6
Alimina Awen,Dehong Hu,Duyang Gao,Zihang Wang,Yayun Wu,Hairong Zheng,Lina Guan,Yuming Mu,Zonghai Sheng
Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine–arginine–glutamate–lysine–alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.
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Regenerative Biomaterials
·
2022
·
IF 5.763
Xu Pei-Yao,Kankala Ranjith Kumar,Li Yue-Wei,Wang Shi-Bin,Chen Ai-Zheng
Despite the success, it is highly challenging to battle against pathogenic biofilms-based chronic bacterial infections by conventional antibiotic therapy. Herein, we report a near-infrared (NIR)/acid-induced nanoplatform based on chitosan (CS)-coated indocyanine green (ICG, photosensitizer)/luteolin (LUT, a natural quorum sensing inhibitor) nanocomposites (ICG/LUT-CS) as antibacterial and antibiofilm agents for skin wound healing. Initially, the ICG/LUT nanoplatforms are prepared by the supercritical antisolvent technology and coated with the CS layer. The obtained ICG/LUT-CS with ultra-high encapsulation efficiency exhibited more favorable photothermal conversion effects and improved NIR laser/acid dual-induced drug release behavior than individual modalities, achieving exceptional bacteria-killing and biofilm elimination effects. Moreover, the ICG/LUT-CS realized the synergetic effects of chemotherapy and photothermal therapy outcomes for wound healing. Together, our findings provided an appealing strategy for the rapid preparation and future translational application of ICG/LUT-CS as an ideal agent for fighting against biofilm infections.
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Frontiers in Oncology
·
2022
·
IF 5.738
Zhang Xuemei,Yan Ziyu,Meng Zhaowei,Li Ning,Jia Qiang,Shen Yiming,Ji Yanhui
Objectives: Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC.Methods: 131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels.Results: The synthesized nanoparticles had a suitable size (25–45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4–6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser.Conclusions: In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Tongtong Hou,Xu Shao,Minling Ding,Kun Mei,Xin Wang,Ping Guan,Xiaoling Hu
Photoinduced modulation of A β 42 aggregation has emerged as a therapeutic option for treating Alzheimer's disease (AD) due to its high spatiotemporal controllability, noninvasive nature, and low systemic toxicity. However, existing photo-oxidants have the poor affinity for A β 42 , low depolymerization efficiency, and difficulty in crossing the blood-brain barrier (BBB), hindering their application in the treatment of AD. Here, through hydrophobic interactions and hydrogen bonding, we integrated the near-infrared (NIR) photosensitizer indocyanine green with transferrin (denoted as TF-ICG), a protein with a high affinity for A β 42 , and demonstrated its anti-amyloid activity in vitro. TF-ICG was shown to bind to A β 42 residues via hydrophobic interaction, impeding π-π stacking of A β 42 peptide monomers and disassembling mature A β 42 protofibrils in a concentration-dependent manner. More importantly, under NIR (808 nm, 0.6w/cm 2 ) irradiation, TF-ICG completely inhibited the fibrillation process of A β 42 to generate amorphous aggregates, with an inhibition rate of 96 % at only 65 nM. Meanwhile, TF-ICG could photo-oxidize rigid A β 42 aggregates and break them down into small amorphous structures. Tyrosine fluorescence assay further demonstrated the intrinsic affinity and targeting of TF-ICG to A β 42 fibrils. In vitro studies validated the anti-amyloid activity of TF-ICG, which provided a theoretical basis for further in vivo application as a BBB-penetrating nanotherapeutic platform.
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Crystals
·
2023
·Vol. 13
·期 9
·1387
·
IF 2.7
Qifa Song,Zi-You Ding,Chengyu Li,Yiran Fan,Xinli Tang,Yingchao Han
Indocyanine green (ICG) shows promise for diagnosing and treating tumors due to its good photothermal and fluorescent properties. In this study, sodium heparin (SH)-stabilized ICG/nano-hydroxyapatite (SH-ICG/nHAP) suspension was ultrasonically prepared to achieve photothermal and photodynamic collaborative therapy (PTT/PDT) for treating tumors. The nHAP had a short rod-like shape and a drug-loading capacity of 13.3% for ICG, corresponding to a drug-loading efficiency of 88.6%. In addition, the SH-ICG/nHAP suspension showed a very low release of ICG in PBS (7.4) and a slightly improved release in acidic buffers (6.5, 5.5), indicating an excellent binding ability of nHAP for ICG. The resulting SH-ICG/nHAP showed good suspension stability. Under an 808 nm near-infrared (NIR) laser, SH-ICG/nHAP showed good photothermal properties and could produce reactive oxygen species (ROS). Under the irradiation of an 808 nm NIR laser at 0.8 W/cm2for 5 min, SH-ICG/nHAP was found to significantly inhibit HepG2 cells proliferation (78.58%), similar to free ICG.In vivo, SH-ICG/nHAP was found to exert an improved inhibitory effect on tumor growth compared to free ICG. Biocompatible and stable SH-ICG/nHAP suspension like this could be a promising system for the PTT/PDT of tumors.Keywords:ICG;nano-hydroxyapatite;suspension;PTT;PDT
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Acta Biomaterialia
·
2018
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IF 6.383
Peng Xue,Mengmeng Hou,Lihong Sun,Qian Li,Lei Zhang,Zhigang Xu,Yuejun Kang
Indocyanine green (ICG) is an efficient photosensitizer that can facilitate producing cytotoxic reactive oxygen species (ROS). At the same time, ICG also has characteristic absorption of near-infrared light and thus can induce a strong photothermal effect. Both of these important features of ICG may be applied for noninvasive light-induced tumor ablation. On the other hand, ICG is lack of stability in blood circulation and susceptible to aggregation or premature clearance from the body. These issues need to be effectively addressed before antitumor application of ICG becomes possible. Herein, a nanocomposite consisting of calcium carbonate modified magnetic polydopamine (PDA) nanoparticles and loaded with ICG, namely Fe 3 O 4 @PDA@CaCO 3 /ICG (FPCI) NPs, was developed to integrate the photothermal capability of PDA with the photodynamic capability of ICG. Particularly, calcium carbonate not only entrapped ICG in the form of stable aggregate to evade blood clearance , but also facilitated controlled release of ICG in response to acidic tumor microenvironment via self-decomposition. With the aid of magnetic guidance, this multifunctional therapeutic agent makes it possible to achieve the combination of photothermal (PTT) and photodynamic therapies (PDT) against tumors, which was demonstrated by this proof-of-concept study based on in vitro and in vivo tumor models. Statement of Significance Currently, there is an ongoing trend of realizing precise and targeted tumor therapy using functional nanocomplexes. Magnetic particles, which can be manipulated by a magnetic field, have attracted increasing attention for tumor therapy. This submitted work demonstrated that calcium carbonate nanoshell was precipitated onto magnetic nanocores mediated by polydopamine. Moreover, indocyanine green (ICG), as a potent photosensitizer, was embedded in this nanocomplex and protected by the calcium carbonate nanoshell, resulting in high drug loading efficiency and enhanced drug stability on the carrier. This new nanocomposite was demonstrated to achieve controlled and pH-responsive release of ICG in tumor environment. This work explored the relationship between the physiochemical properties of the nanocomplex and their potential biomedical applications, aiming to inspire the development of analogous nanoplatforms featured with calcium carbonate blocks.
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Regenerative Biomaterials
·
2025
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IF 8.1
Feng Xinyu,Liu Ruihan,Zhang Cai,Cheng Ran,Fu Dianxun,Sun Shaokai,Wang Junping,Wang Guohe
Bioadhesives are being increasingly used in clinical practice, but pose significant health risks due to their uncontrollable intraoperative leakage. Nevertheless, there is currently a critical lack of effective solutions. Herein, we propose a second near-infrared window (NIR-II) fluorescence-visible indocyanine green (ICG)-BioGlue adhesive for precision surgical adhesion with intraoperative leakage prevention. The fabricated ICG-BioGlue adhesive based on the non-covalent interaction exhibits nearly 100% fluorescence labeling efficiency and maintains long-term stable NIR-II fluorescence for up to 3 months. During surgery, ICG-BioGlue adhesive enables real-time visualization of wound adhesion in various fields such as aortic dissection adhesion and liver or kidney wound hemostasis, preventing leakage into surrounding tissues. Moreover, the stable fluorescence of ICG-BioGlue adhesive allows effective imaging-guided removal of long-term adhesive fragments in the body when they cause compression symptoms after surgery. Considering it consists solely of Food and Drug Administration-approved drugs ICG and BioGlue, with a straightforward synthesis method and versatile applicability, ICG-BioGlue adhesive holds excellent potential for clinical translation. Our study provides a leakage-preventing strategy to enhance biosafety and promote the widespread application of bioadhesives in clinical settings.
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International Journal of Nanomedicine
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2023
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IF 8
Jingmou Yu,Liangliang Wang,Xin Xie,Wenjing Zhu,Zhineng Lei,Linghui Lv,Hongling Yu,Jing Xu,Jin Ren
Background Multifunctional stimuli-responsive nanoparticles with photothermal-chemotherapy provided a powerful tool for improving the accuracy and efficiency in the treatment of malignant tumors.Methods Herein, photosensitizer indocyanine green (ICG)-loaded amorphous calcium-carbonate (ICG@) nanoparticle was prepared by a gas diffusion reaction. Doxorubicin (DOX) and ICG@ were simultaneously encapsulated into poly(lactic-co-glycolic acid)-ss-chondroitin sulfate A (PSC) nanoparticles by a film hydration method. The obtained PSC/ICG@+DOX hybrid nanoparticles were characterized and evaluated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The cellular uptake and cytotoxicity of PSC/ICG@+DOX nanoparticles were analyzed by confocal laser scanning microscopy (CLSM) and MTT assay in 4T1 cells. In vivo antitumor activity of the nanoparticles was evaluated in 4T1-bearing Balb/c mice.Results PSC/ICG@+DOX nanoparticles were nearly spherical in shape by TEM observation, and the diameter was 407 nm determined by DLS. Owing to calcium carbonate and disulfide bond linked copolymer, PSC/ICG@+DOX nanoparticles exhibited pH and reduction-sensitive drug release. Further, PSC/ICG@+DOX nanoparticles showed an effective photothermal effect under near-infrared (NIR) laser irradiation, and improved cellular uptake and cytotoxicity in breast cancer 4T1 cells. Importantly, PSC/ICG@+DOX nanoparticles demonstrated the most effective suppression of tumor growth in orthotopic 4T1-bearing mice among the treatment groups. In contrast with single chemotherapy or photothermal therapy, chemo-photothermal treatment by PSC/ICG@+DOX nanoparticles synergistically inhibited the growth of 4T1 cells.Conclusion This study demonstrated that PSC/ICG@+DOX nanoparticles with active targeting and stimuli-sensitivity would be a promising strategy to enhance chemo-photothermal cancer therapy.
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BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Yun Lu,Lan Chen,Zhouxue Wu,Ping Zhou,Jie Dai,Jianmei Li,Qian Wen,Yu Fan,Fancai Zeng,Yue Chen,Shaozhi Fu
Breast cancer is characterized by insidious onset, rapid progression, easy recurrence, and metastasis. Conventional monotherapies are usually ineffective due to insufficient drug delivery. Therefore, the combination of multimodal therapy with tumor microenvironment (TME)-responsive nanoplatforms is increasingly being considered for the targeted treatment of breast cancer. We synthesized bioactive hybrid nanoparticles for synergistic chemotherapy and photothermal therapy. Briefly, doxorubicin (DOX) and indocyanine green (ICG)-loaded nanoparticles (DI) of average particle size 113.58 ± 2.14 nm were synthesized, and their surface were modified with polydopamine (PDA) and attached to the anaerobic probiotic Bifidobacterium infantis (Bif). The bioactive Bif@DIP hybrid showed good photothermal conversion efficiency of about 38.04%. In addition, the self-driving ability of Bif allowed targeted delivery of the PDA-coated DI nanoparticles (DIP) to the hypoxic regions of the tumor. The low pH and high GSH levels in the TME stimulated the controlled release of DOX and ICG from the Bif@DIP hybrid, which then triggered apoptosis of tumor cells and induced immunogenic cell death (ICD), resulting in effective and sustained anti-tumor effect with minimum systemic toxicity. Thus, the self-driven Bif@DIP hybrid is a promising nanodrug for the targeted chemotherapy and photothermal therapy against solid cancers.
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Materials Today Communications
·
2020
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IF 2.678
Renlu Han,Sheng Wu,Yuyan Yan,Wei Chen,Keqi Tang
Near-infrared (NIR) light responsive multifunctional nanoparticles were constructed by ferrocene modified, indocyanine green (ICG) loaded and β-cyclodextrin (β-CD) capped mesoporous silica (MSN) for collaborative chemodynamic/ photothermal/photodynamic (CDT/PTT/PDT) therapy in vitro. In the multifunctional nanoparticles , the covalently conjugated ferrocene was acted as a catalyst for converting the high level of intracellular hydrogen peroxide (H 2 O 2 ) into high-toxic hydroxyl radical ( OH), the encapsulated ICG was served as both photothermal agent and photosensitizer to generate hyperpyrexia and singlet oxygen ( 1 O 2 ) respectively by absorbing NIR light, and the outmost β-CD was worked as a shielding layer to prevent ICG from leakage and improve the dispersity of as-prepared nanoparticles . After the nanoparticles were endocytosed by cancer cells, the hyperpyrexia generated by ICG upon NIR light irradiation not only is able to directly kill cancer cells for photothermal therapy (PTT), but also enables to dissociate the capped β-CD and thus expose the inner ferrocene. On this basis, the exposed ferrocene could convert the intracellular H 2 O 2 into toxic OH via ferrocene-mediated Fenton reaction for efficiently killing cancer cells (chemodynamic therapy, CDT). Moreover, the generated 1 O 2 by ICG could further kill the cancer cells for photodynamic therapy (PDT) in a collaborative way. The results of in vitro experiments suggest that the collaborative CDT/PTT/PDT shows significantly amplified inhibition rate of HeLa cells compared to single CDT or dual PTT/PDT, endowing the multifunctional nanoparticles with great potential in cancer synergistic treatments.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2019
·
IF 3.532
Meng Wang,Yi Xiao,Ying Li,Jiahe Wu,Fangyuan Li,Daishun Ling,Jianqing Gao
The nucleus is in charge of the metabolism and heredity of the cell, and genetic mutations are closely related with tumour multidrug resistance (MDR). Indocyanine green (ICG), the FDA-approved photosensitizer , is widely used for tumour photodynamic therapy (PDT) and photothermal therapy (PTT). Few studies have clarified the cellular distribution of ICG in MDR tumour cells. In the study, ICG distribution was detected in the whole tumour cells of MCF-7 and MCF-7/ADR, especially in the nucleus, which led us to question whether increasing cellular accumulation and nuclear distribution of ICG could be a potential method to overcome MDR. Therefore, a reactive oxygen species (ROS) and near-infrared (NIR) light dual-responsive nanohybrid was constructed with diselenide cross-linked polyamidoamine-Poloxamer 188 and graphene oxide with ICG as payloads (ICG/GPP). The nanohybrid enhanced the stability of ICG and showed an ROS-sensitive release behaviour. More ICG was delivered by ICG/GPP to the MCF-7/ADR cells. After escaping from the lysosome, nuclear accumulation of ICG was increased. Under NIR laser irradiation, ICG/GPP showed increased cytotoxicity for the combined PTT and PDT in MCF-7/ADR cells. Moreover, the expression of P-glycoprotein (P-gp) was suppressed to overcome tumour MDR. The ROS- and NIR- responsive GPP shows potential for the nuclear delivery of drugs to combat tumour MDR.
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