Theranostics
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2026
·Vol. 16
·期 10
·5278
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IF 14.9
Ziyao Wang,Yongchao Yao,Ziyan Feng,Yulong Liao,Liyun Wang,Xueyang Xiao,Wenchuang Hu,Zhiyong Qian,Li Qiu
Rationale Sonodynamic therapy (SDT) has emerged as a promising strategy for melanoma treatment because of its noninvasive nature, deep penetration and potential to activate antitumor immunity. However, the uncontrollable delivery and limited tumor accumulation of sonosensitizers often restrict SDT efficacy. And tumor cells tend to activate cytoprotective autophagy under SDT-induced oxidative stress, which may further compromise treatment outcomes. Developing an image-guided drug delivery system with the function of enhancing SDT efficacy offers a promising strategy for melanoma management. Methods We developed a new ultrasound (US)-responsive lipoic acid-based nanodroplets loaded with perfluoropentane (PFP) and sonosensitizer Chlorin e6 (LA@P-Ce6 NDs). The physicochemical properties, acoustic droplet vaporization (ADV) behavior, and biosafety of LA@P-Ce6 NDs were systematically evaluated. Contrast-enhanced ultrasound (CEUS) and photoacoustic (PA) imaging were conducted both in vitro and in vivo to evaluate multimodal imaging ability. Antitumor effects and mechanisms of LA@P-Ce6 NDs under US irradiation were investigated both in vitro and in vivo , as well as their ability to activate antitumor immunity. Results LA@P-Ce6 NDs exhibited excellent stability under physiological conditions and underwent effective ADV, enabling CEUS and PA imaging both in vitro and in vivo . Under therapeutic US, Ce6 induced strong ROS production and LA modulated autophagic flux, synergistically achieving enhanced oxidative damage at the irradiated site and promoting ICD. Our treatment showed significant antitumor ability and induced strong antitumor immune effect, which was able to suppress pulmonary metastasis. Conclusions This study presented a multifunctional LA@P-Ce6 NDs system that enabled autophagy-modulated, CEUS/PA image-guided SDT. The integration of multimodal imaging and synergistic antitumor therapy offers a promising melanoma management method.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Yuanyuan Liu,Yuanyao Lin,Xuemei He
An ultrasound-responsive PLGA nanosystem co-encapsulating CXB, CAT, and PFP was developed. • Ultrasound triggered PFP phase transition and promoted on-demand CXB release from nanoparticles. • CAT retained catalytic activity and enabled oxygen generation, helping alleviate tumor hypoxia. • The nanosystem potentiated the antitumor activity of imatinib against GIST in vitro and in vivo. • Combined treatment increased apoptosis and suppressed migration and tumor growth in GIST. The therapeutic efficacy of imatinib (IM) in gastrointestinal stromal tumors (GISTs) is often limited by inadequate intratumoral drug accumulation and an abnormal tumor microenvironment. In this study, an ultrasound-responsive poly(lactic-co-glycolic acid) (PLGA) nanoparticle system, designated CXB/CAT@PFP-PLGA NPs, was developed for the co-delivery of celecoxib (CXB) and catalase (CAT) to enhance the antitumor efficacy of IM. The nanoparticles were characterized in terms of their physicochemical properties, ultrasound responsiveness, and oxygen-generating capability. Their ability to potentiate IM therapy was evaluated both in vitro and in vivo, while biodistribution and biosafety were assessed in vivo. The results showed that CXB/CAT@PFP-PLGA NPs exhibited a relatively uniform size distribution and successfully co-encapsulated CXB and CAT. Upon ultrasound irradiation, the nanoparticles underwent phase transition, thereby triggering drug release. In vitro, CXB/CAT@PFP-PLGA NPs enhanced the inhibitory effect of IM by reducing cell viability, promoting apoptosis, and inhibiting cell migration. In vivo, the nanosystem improved the antitumor efficacy of IM, accumulated at the tumor site, suppressed tumor growth, and showed no evident systemic toxicity. Collectively, these findings suggest that CXB/CAT@PFP-PLGA NPs may represent a promising strategy for enhancing IM therapy in GIST. Download: Download high-res image (89KB) Download: Download full-size image
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Binrui Shi,Mingjie Li,Renjie Feng,Guihua Wang,Liyong Deng,Yueyong Li,Kezhen Wang,Meng Du,Zhiyi Chen
Purpose: Melanoma, a highly aggressive superficial malignancy with rising incidence and mortality, faces limited sonodynamic therapy (SDT) efficacy due to poor sonosensitizer accumulation and penetration. To overcome this, we employed chlorin e6 (Ce6), a high-ROS-yield sonosensitizer, and enhanced its tumor delivery using a synergistic microneedle (MN) and ultrasound (US) strategy.Methods: Using melanoma as an application scenario, a “stepwise drug delivery” system was developed. It consisted of dissolving MN encapsulating US-responsive nanoparticles (Ce6-PFP@PLGA, CPP) and termed CPP@MN. CPP@MN breaks through the stratum corneum to deliver CPP to tumors, followed by US-triggered cavitation that mediates perfluoropentane (PFP) phase transition to enhance the tumor-penetrating capability of chlorin e6 (Ce6). Delivery efficacy was validated using three experimental models: an in vitro agarose skin phantom, ex vivo pig skin, and in vivo tumors. Furthermore, the anti-tumor efficacy of US-combined CPP@MN was evaluated at the cellular level and in tumor-bearing mice.Results: According to the results, CPP@MN showed excellent transdermal performance, including rapid dissolution of sonosensitizer and sufficient mechanical strength. MN combined with US increased the tumor penetration depth of loading drug by 2.5– 4 times across all experimental models. Ultrasonic cavitation promotes nanoparticle-derived Ce6 release and deeper tumor diffusion, resulting in specific anti-tumor efficacy.Conclusion: This innovative “stepwise drug delivery” system addresses persistent challenges in superficial tumor SDT, including inadequate sonosensitizer aggregation and poor tissue penetration, while establishing a multifunctional platform for spatiotemporally controlled drug release that sequentially overcomes the skin biological barriers.
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Zhezhu Nan,Linrong Shi,Hengyu Liu,Xinyue Han,Junjie Chen,Daocheng Wu,Mingxi Wan,Yi Feng
High-intensity focused ultrasound (HIFU) has been employed in clinical practice for tumor treatment via thermal ablation. However, the high energy requirements of HIFU raise safety concerns, and insufficient therapeutic efficacy can lead to potential tumor recurrence. To address these issues, we developed multifunctional theranostic nanoparticles (PFP@POMP@MnO2–Ce6 NPs) and utilized dual-frequency HIFU technology to enhance therapeutic efficiency at lower energy levels. This approach achieved efficient and rapid thermal/cavitation/sonodynamic synergistic therapy, leveraging long-term therapy through immune responses and precise monitoring via US/MRI dual-modal imaging. The NPs are composed of polymer micelles that encapsulate perfluoropentane (PFP), with their surface modified by MnO2 and sonosensitizer Chlorin e6 (Ce6). The results indicated that dual-frequency HIFU irradiation triggered the vaporization of PFP within the NPs, enhancing both the thermal and cavitation effects of HIFU, which led to an increase in the area of thermal damage in the phantoms. In vitro and in vivo experiments demonstrated that the NPs, when combined with dual-frequency HIFU, could achieve synergistic antitumor effects, inducing 94.1 ± 1.5% (p < 0.01) tumor cell death in vitro and ablation of directly treated tumors without recurrence in vivo. Most interestingly, the synergistic therapy suppressed the growth of distal tumors (93.4 ± 1.1% growth inhibition), indicating enhanced immune responses, which was further supported by immunohistochemical (IHC) results of a 69.3 ± 1.5% increase in CD8+ T cell infiltration and a 61.2 ± 1.5% increase in F4/80+ macrophage infiltration. It ensured the longevity of the treatment effects and reduced the likelihood of tumor recurrence. Moreover, the NPs’ dual-modal imaging (US/MRI) capabilities provided real-time guidance and improved tumor visualization, confirming their utility as potent theranostic agents. This therapeutic approach, facilitated by multifunctional nanoparticles and in synergy with dual-frequency HIFU, provided precise imaging guidance, enhanced therapeutic efficacy, and elicited an immune response, thereby effectively addressing the limitations inherent to traditional HIFU therapy.
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Cancer Treatment and Research Communications
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2026
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IF 3.5
Bo Ren,Han-mei Li,Ju-ying Zhang,Jiawei Wang,You Yang,Li-tao Ye,Jinhong Yu,Jian Xu,Gang Quan,Jingdong Li,Wong Charng Choon
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most malignant tumours with limited treatment options and poor prognosis. This study designed a targeting nanoplatform, GCP@NBs, combining paclitaxel (PTX)-mediated chemotherapy and chlorin e6 (Ce6)-assisted sonodynamic therapy (SDT) for PDAC. In vitro targeting ability was validated via glypican-1 antibodies (GPC1-Abs) on the surface. Phase transition of perfluoropentane (PFP) facilitated the ultrasound (US) imaging and the controlled drug release. Live/Dead Cell Dual-fluorescence Staining and flow cytometry were performed to corroborate cell apoptosis. Meanwhile, the generation of reactive oxygen species (ROS) was confirmed by ROS Content Detection Kit. Mitochondrial Membrane Potential (MMP) Assay Kit was leveraged to verify the depolarization of MMP, and western blot was performed to reveal the expression of proteins involved in apoptosis. Additionally, biosafety of GCP@NBs in the absence of US irradiation was validated. Consequently, GCP@NBs exhibited optimal particle size of 378.4 ± 10.54 nm and surface charge of -22.63 ± 0.32 mV, showing excellent stability and drug loading capacity (47.35 ± 0.21% for Ce6 and 64.80 ± 0.19% for PTX). GCP@NBs showed good biosafety and US imaging capability, exhibited specific targeting ability and cellular uptake, demonstrated efficient drug release and US-responsive ROS generation, and achieved excellent anti-cancer effects at low concentration. JC-1 staining showed the obvious MMP depolarization, and Western blot illustrated the increased expression of caspase-3 and Bax/Bcl-2 ratio during the cell apoptosis process. This study highlights the potential of GCP@NBs as novel and highly effective nanoplatforms for treatment of PDAC.
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Acta Biomaterialia
·
2026
·
IF 9.6
Yaqian Du,Zixuan Huang,Xiaodan Xu,Yijie Chen,Jifan Chen,Tao Lin,Lina Tang,Guowei Wang,Pintong Huang
The lack of pain management for advanced pancreatic cancer resulted in severe suffering for patients at the final stage of life. Pain relief can be achieved through local injection of nerve-blocking agents, but the efficiency was attenuated by perineural barriers due to drug could hardly penetrate into peripheral nerves. To address this challenge, we here proposed a strategy of ultrasound-mediated blockade of nociceptive transmission for treating the cancer pain. To demonstrate the feasibility and effectiveness of the method, a kind of transferrin-modified liposome (TLAP) loaded with AZ23 (a TrkA inhibitor) and perfluoropentane was developed and capable of ultrasound imaging guidance and ultrasonic cavitation. After local injection around the pancreatic cancer, TLAP targets the nerves via recognizing transferrin receptor, and transforms from nanosized liposome into microbubble via liquid-to-gas phase transition when exposed to ultrasound irradiation. The following ultrasonic cavitation opens the perineural barriers, and facilitates AZ23 delivery into the nerve interior, which can be visualized under ultrasound imaging, and leads to superior efficacy of pain relief in mouse cancer pain model of pancreatic cancer. In addition, sustained retention at the injection site can be maintained for over two days, and analgesia is further reinforced through repeated ultrasound exposures, enabling effective and intensity-tunable pain control. Meanwhile, no significant systemic or local tissue damage was observed after treatment. This study presents an effective strategy to tackle the perineural barriers and provides an effective nanoplatform for cancer pain management using ultrasound. Statement of Significance Pain relief of pancreatic cancer patients can be achieved through local injection of nerve-blocking agents, but the efficiency is attenuated by perineural barriers due to drug could hardly penetrate into peripheral nerves. This study developed a kind of transferrin-modified liposome (TLAP) loaded with a TrkA inhibitor and perfluoropentane to achieve ultrasonic cavitation-induced perineural barriers destruction, and ultrasound-guided cancer pain management, which led to superior efficacy of pain relief in cancer pain model of pancreatic cancer. This study presents an effective strategy of ultrasound-mediated blockade of nociceptive transmission to tackle the perineural barriers and provides an effective nanoplatform for cancer pain management of pancreatic cancer using ultrasound.
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ACS Applied Nano Materials
·
2026
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IF 5.8
Yanping Chen,Baoru Fang,Ke Wang,Siqi Geng,Fang Wang,Lin Xu,Zhiqiu Ye,Fei Xu,Zhangsen Yu
Radiofrequency ablation (RFA), a widely used minimally invasive therapy for primary liver cancer, induces tumor cell necrosis and immunogenic cell death, thereby activating antitumor immunity. However, its efficacy is often compromised by incomplete ablation of marginal regions and insufficiently robust immune activation, leading to a high risk of post-treatment recurrence and metastasis. Currently, integrating RFA with multifunctional nanomedicines is a promising strategy to overcome these limitations. Herein, we developed a multifunctional, targeted thermosensitive ultrasound contrast agent, termed TUCA(R837)-SP94, for synergistic RFA/immunotherapy against hepatocellular carcinoma (HCC). TUCA(R837)-SP94 integrates three major innovations: (1) tumor-targeting via the SP94 peptide enables enrichment at tumor sites; (2) under the thermal effects of RFA, the loaded perfluoropentane (PFP) undergoes a liquid–gas phase transition, enhancing the ultrasound contrast imaging effect; (3) RFA thermal effects trigger liposome release of imiquimod (R837). This study prepared TUCA(R837)-SP94 via the thin-film hydration method and characterized it, evaluated its ultrasound imaging performance and in vitro immune responses, and systematically investigated the synergistic therapeutic effects and immunomodulatory mechanisms of TUCA(R837)-SP94 combined with RFA through the establishment of mouse models of in situ and metastatic hepatocellular carcinoma. Results indicate that TUCA(R837)-SP94 combined with RFA significantly inhibits tumor growth both in situ and distally. This approach promotes DC maturation, increases the ratio of cytotoxic T cells to helper T cells in the tumor region, and reduces the proportion of regulatory T cells, while demonstrating excellent biosafety. Collectively, TUCA(R837)-SP94-based RFA/immunotherapy synergistic treatment represents a safe and effective theranostic platform for hepatocellular carcinoma, demonstrating promising potential for clinical translation and application.
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International Journal of Nanomedicine
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2024
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IF 6.6
Xiaoyi Tang,Yijia Liu,Mengxin Zhao,Lei He,Jiahao Guo,Tian Wang,Wei Li,Jiaqi Zhao
Purpose This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention.Methods We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery.Results The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA’s potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure’s efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation.Conclusion The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.
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JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Min Liao,Qi Zhang,Jianbo Huang,Xiaotong Huang,Chong Cheng,Juan Tu,Dong Zhang,Qiang Lu,Lang Ma
Owing to the dense extracellular matrix and high interstitial fluid pressure in the tumor microenvironment, methods which enhance the permeation and retention of nano drugs into liver tumors remain unsatisfactory for successful tumor treatment. We designed a near-infrared (NIR)- and ultrasound (US)-triggered Pt/Pd-engineered “cluster bomb” (Pt/Pd-CB) which actively penetrates liver cancer cell membranes and achieves photothermal and sonodynamic therapy (SDT). The physical forces generated by the fast expansion and collapse of perfluoropentane nanodroplets eject “sub bombs” (Pt/Pd nanoalloys) into liver cancer cells upon activation by NIR and US. Pt/Pd nanoalloys can then convert H 2 O 2 into O 2 to alleviate hypoxia and boost SDT efficiency while exhibiting a highly efficient photothermal response under NIR irradiation. Our findings might especially be promising for the treatment of solid tumors.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Lihui Yuwen,Yuan Liu,Qi Zhang,Xiaoxiao Xu,Liang Lu,Yirui Qiusong,Wen Li,Dongliang Yang,Lianhui Wang
Bacteria colonizing medical implants usually lead to biofilm formation and result in persistent infections. Conventional antibiotics often fail to effectively accumulate and penetrate the extracellular polymeric barriers of bacterial biofilms. Thus, there is an urgent need to develop effective antibiotic delivery systems capable of biofilm targeting and disruption. Herein, mesoporous Fe 3 O 4 nanoparticles (mFe NPs) were used to co-load perfluoropentane (PFP) and ciprofloxacin (Cip), constructing magnetic field (MF)/ultrasound (US) dual-responsive mFeP-Cip NPs for eradicating Pseudomonas aeruginosa (PAO1) biofilms on catheter implants. Under magnetic guidance, mFeP-Cip NPs can precisely target PAO1 biofilms. Subsequent US exposure triggers PFP phase transition and vaporization, which disrupts biofilm structure via cavitation effects, thereby enhancing Cip penetration. In a 96-well plate PAO1 biofilm model, the combination of mFeP-Cip NPs with MF/US reduced biofilm biomass and viable bacterial counts by 59 % and 99.9992 %, respectively, while demonstrating efficient biofilm elimination on medical catheters. In a catheter PAO1 infection model in mice, mFeP-Cip NPs achieved a 99.994 % antibacterial efficiency under MF/US stimulation. Additionally, mFeP-Cip NPs exhibited excellent biocompatibility. This work presents an MF/US dual-responsive antibiotic delivery system that synergizes magnetic targeting with US-enhanced antibiotic permeation, offering a promising nanotherapeutic platform for precise and efficient treatment of biofilm-associated infections.
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Biomaterials Science
·
2025
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IF 5.7
Yan Long,Shigen Zhong,Fang Li,Wei Zhang,Yaqin Hu,Mingyuan Dai,Min Zheng,Long Cheng,Haitao Ran
Early non-invasive diagnosis of liver fibrosis remains a significant clinical challenge. This study aimed to develop type IV collagen-targeted phase-change nanoparticles (AC-IV-PFP@NPs) for ultrasound molecular imaging (UMI), allowing accurate staging of early-stage liver fibrosis. AC-IV-PFP@NPs were prepared by conjugating anti-collagen IV antibody (AC-IV) to perfluoropentane-encapsulated liposomes via carbodiimide coupling. Physicochemical properties were characterized using transmission electron microscopy, dynamic light scattering, and confocal microscopy. In CCl4-induced fibrotic rats representing METAVIR stages S0–S4, the targeted nanoparticles were administered intravenously. The nanoparticles displayed spherical morphology with a mean diameter of 307.92 ± 4.16 nm, high AC-IV conjugation efficiency (78.94 ± 2.83%), and a favorable biosafety profile (cell viability >87% at 6 mg mL−1). Targeting specificity was validated both in vitro and in vivo, with fluorescence imaging showing a 3.8-fold increase in binding to fibrotic collagen IV relative to non-targeted controls (P < 0.001). CEUS signal intensity peaked at 30 min post-injection and showed a strong positive correlation with the fibrosis stage (r = 0.725, P < 0.001). ROC analysis demonstrated high diagnostic accuracy for early fibrosis: an area under the curve (AUC) of 0.949 for distinguishing S0 from S1–S4 (sensitivity 85.5%, specificity 91.7%) and an AUC of 0.923 for separating S0–S1 from S2–S4 (sensitivity 90.7%, specificity 79.2%). To date, AC-IV-PFP@NPs represent the first type IV collagen-targeted UMI platform for liver fibrosis staging in rats, offering non-invasive, real-time assessment with high sensitivity for early-stage disease (S1–S2). This approach addresses the limitations of biopsy and conventional imaging and offers a promising and transformative approach for clinical fibrosis management.
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Drug Delivery and Translational Research
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2025
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IF 5.5
Peng Wangrui,Goh MeeiChyn,Lan Jie,Du Meng,Chen Zhiyi
Dissolving microneedles (DMNs) are an emerging transdermal drug delivery system that has gained increasing attention as an alternative to traditional oral and injectable methods for treating rheumatoid arthritis (RA). However, these DMNs encounter challenges related to insufficient drug diffusion through passive mechanisms. To address this issue, we developed biocompatible DMNs fabricated from hyaluronic acid (HA) loaded with ultrasound-responsive nanoparticles, aiming at enhancing drug permeation and diffusion through ultrasound (US) assistance. Methotrexate (MTX), a first-line treatment for RA, was encapsulated in poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles containing perfluoro-n-pentane (PFP), referred to as MTX-PFP-NPs. These nanoparticles were then incorporated into DMNs, designated as MTX-PFP-NPs@DMNs. Under the cavitation effect of ultrasound, PFP undergoes a phase transition that facilitates drug release and diffusion. The synergistic effect of the DMNs system and US were demonstrated in both an ex-vivo rat skin model and a collagen-induced arthritis (CIA) mouse model. The MTX-PFP-NPs@DMNs exhibited sufficient mechanical strength to penetrate the stratum corneum and dissolve completely within 20 min, enabling effective drug delivery. The synergistic effect of the DMNs system and US was evidenced by enhanced FITC penetration and diffusion in the ex-vivo rat skin model. Additionally, in vivo studied showed improved therapeutic efficacy in reducing joint swelling, bone erosion, cartilage damage, and pro-inflammatory cytokines level compared to only MTX-PFP-NPs@DMNs. This research underscores the promising integration of DMNs technology and US, offering a high-compliance approach to transdermal drug delivery that could significantly improve treatment outcomes for chronic conditions like RA. Graphical
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