Journal of Nanobiotechnology最新文献

{"title":"Biomimetic gene delivery system coupled with extracellular vesicle-encapsulated AAV for improving diabetic wound through promoting vascularization and remodeling of inflammatory microenvironment.","authors":"Shan He, Zhenhao Li, Lei Xie, Rongtian Lin, Biying Yan, Bixiang Li, Lingxi Luo, Youshan Xv, Huangding Wen, Yaxuan Liang, Cong Huang, Zhiqing Li","doi":"10.1186/s12951-025-03261-w","DOIUrl":"10.1186/s12951-025-03261-w","url":null,"abstract":"<p><p>Adeno-associated virus (AAV)-mediated gene transfer has demonstrated potential in effectively promoting re-epithelialization and angiogenesis. AAV vector has a safety profile; however, the relatively low delivery efficacy in chronic wound with an inflammatory microenvironment and external exposure has limited its prospective clinical translation. Here, we generated AAV-containing EVs (EV-AAVs) from cultured HEK 293T cells and confirmed that the gene transfer efficiency of VEGF-EV-AAV significantly surpassed that of free AAV. Subsequently, a biomimetic gene delivery system VEGF-EV-AAV/MSC-Exo@FHCCgel developing, and synergistically enhances anti-inflammation and transfection efficiency in the combination of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exo). Upon reaching physiological temperature, this hydrogel system transitions to a gel state, maintaining AAV bioactivity and facilitating a sustained release of the encapsulated vesicles. The encapsulation strategy enables the vesicles to rapidly fuse with endothelial cell membranes, ensuring controlled expression of endogenous VEGF. Results revealed that VEGF-EV-AAV/MSC-Exo@FHCCgel alleviates mitochondrial function in endotheliocyte under oxidative stress. Furthermore, it eliminates senescent macrophages by inhabitation of cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway to promote efferocytosis. The system increases Treg cells accumulation, leading to a reduction of inflammatory cytokines. Collectively, the biomimetic gene delivery system represents a promising multi-faceted strategy for chronic wound healing.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"242"},"PeriodicalIF":10.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printed shape-memory piezoelectric scaffolds with in-situ self-power properties for bone defect repair.","authors":"Bing Li, Yichao Ma, Kanwal Fatima, Xiaojun Zhou, Xin Gu, Shuo Chen, Chuanglong He","doi":"10.1186/s12951-025-03325-x","DOIUrl":"10.1186/s12951-025-03325-x","url":null,"abstract":"<p><p>Electrical stimulation has been shown to regulate early immunity and late-stage osteogenesis in bone repair. However, achieving in-situ electrical stimulation in the form of self-power in vivo during the initial postoperative stages when the patients have limited mobility remains challenging. In this study, we developed a 3D-printed in-situ self-powered composite scaffold composed of shape memory polyurethane elastomers (SMPU) and polyvinylidene fluoride (PVDF) piezoelectric nanofibers. The composite scaffold demonstrates excellent shape memory performance, allowing for minimally invasive implantation. During the shape memory process, the composite scaffold can provide mechanical force stimulation to PVDF nanofibers to generate charge. Therefore, self-power was achieved through the integration of the shape memory process and piezoelectric effects, and it can be used for in-situ electrical stimulation during the initial postoperative period. Additionally, the composite scaffold can output voltage under continuous mechanical force stimulation, indicating that the patients can apply sustained mechanical force stimulation to the composite scaffold to output voltage through rehabilitation exercises when the patients regain mobility. Both cell experiments and animal studies confirmed that this composite scaffold can effectively regulate the immune microenvironment and enhance osteogenesis. This study successfully achieves in-situ electrical stimulation in the form of self-power by integrating the shape memory process and piezoelectric effects, which is expected to be an effective repair strategy for bone tissue engineering.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"244"},"PeriodicalIF":10.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant human collagen hydrogels with different stem cell-derived exosomes encapsulation for wound treatment.","authors":"Xiaoman Zeng, Jingjing Gan, Danqing Huang, Yuanjin Zhao, Lingyun Sun","doi":"10.1186/s12951-025-03319-9","DOIUrl":"10.1186/s12951-025-03319-9","url":null,"abstract":"<p><p>Exosomes-loaded hydrogels have potential value in wound treatment. Current studies focus on improving hydrogels' biocompatibility and optimizing different stem cell-derived exosomes for better therapeutic effect. Herein, we present a novel biocompatible recombinant human collagen (RHC) hydrogel loading with different MSCs-derived exosomes for promoting wound healing. We modify the RHC with methacrylate anhydride (MA) at optimal concentration, generating collagen hydrogel (RHCMA) with ideal physiochemical properties for exosome delivery (MSC-exos@RHCMA). Exosomes derived from human adipose-derived MSCs (ADSC-exos), bone marrow-derived MSCs (BMSC-exos) and umbilical cord MSCs (ucMSC-exos) are harvested from the culture supernatants and are loaded into RHCMA, respectively. These three hydrogel systems exhibit desired sustained release features, and can significantly improve cell proliferation and migration. In addition, these MSC-exos@RHCMAs show excellent therapeutic performance in treating the wounds of rats. Notably, we have demonstrated that the healing effect occurs best under the treatment of ucMSC-exos@RHCMA, following inflammatory resolution, angiogenesis, and collagen formation. These results would supply important value for the clinical application of MSC-exos in wound treatment in the future.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"241"},"PeriodicalIF":10.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-atom Zr doped heterojunction enhanced piezocatalysis for implant infection therapy through synergistic metal immunotherapy with sonodynamic and physical puncture.","authors":"Xing Zhou, Jingbo Xie, Xingchen Zhou, Tianyou Ma, Yichen Lu, Yiwen Yang, Zhefei Xie, Houfu Ling, Rui Xu, Mo Wu, Jinglei Wang, Weixiang Wang, Derong Kong, Pengchao Xu, Xuan Wan, Hongbo Wu, Peijian Tong, Hanting Xia","doi":"10.1186/s12951-025-03309-x","DOIUrl":"10.1186/s12951-025-03309-x","url":null,"abstract":"<p><p>Recent common clinical treatments for implant bacterial infections involve replacing inert implants and using antibiotics. However, these methods remain limited in their effectiveness for pathogen clearance, immune regulation, and osteogenesis. In this study, we developed a Zr-doped heterointerface of SrTiO₃ and Hap (SrTiZrO₃/Hap) heterojunction coating with single-atom Zr doping and heterogeneous interfaces designed for ultrasound-responsive antimicrobial activity and bone formation. Under ultrasound, the mechanical force exerted by SrTiZrO₃/Hap enhances its physical puncture and sonodynamic activity, synergizing with the metalloimmunotherapy effect of Zr⁴⁺ for efficient antimicrobial activity. The primary mechanism enhancing sonodynamic activity involves local interfacial polarization from single-atom Zr doping, achieving piezoelectric catalysis in conjunction with electronic polarization from the built-in electric field. SrTiZrO₃/Hap achieved a 99.3% antibacterial rate against S. aureus and 99.7% against E. coli under ultrasound. Additionally, SrTiZrO₃/Hap promoted osteogenic differentiation after ultrasound irradiation by activating the PI3K/Akt pathway via its piezoelectric, needle-like topological surface and the release of functional ions, thus accelerating bone repair.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"243"},"PeriodicalIF":10.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocomposite-based PCR reactors to enhance thermal rate and fluorescence intensity in hand-held qPCR device.","authors":"Jiyeon Han, Tiara A M, Seongryeong Kim, Gabriela Morales Florez, Kiran Shrestha, Dang Du Nguyen, Inki Kim, Jinkee Lee, Gyoujin Cho","doi":"10.1186/s12951-025-03287-0","DOIUrl":"10.1186/s12951-025-03287-0","url":null,"abstract":"<p><p>A photonic quantitative polymerase chain reaction (qPCR) has usually implemented a polydimethylsiloxane (PDMS) based disposable inexpensive PCR reactor, worked as the photothermal cycler, to show potential as a point-of-care test (PoCT) for detection nucleic acids. However, the PoCT type photonic qPCR has to overcome the prolonged time for the fabrication of PDMS-based PCR reactors and enable a rapid thermal cycler to shorten diagnosis time with a strong fluorescence intensity. Here, we developed a room-temperature curable titanium dioxide (TiO₂) nanoparticle dispersed PDMS (TiO₂-PDMS) nanocomposite to reduce the fabrication time of the PCR reactor which enhanced the speed of photothermal cycles and fluorescence signal intensity of photonic qPCR. The TiO₂-PDMS nanocomposite was formulated for rapid cross-linking at the room-temperature by introducing an optimized amount of Pt catalyst, resulting in the fabrication of a nanocomposite-based PCR reactor within 8 min at room-temperature. The nanocomposite-based PCR reactor enhanced the heating rate to 18.33 Cº/s and cooling rate to -3.11Cº/s because of the phonon scattering effect of TiO₂ in the reactor and successfully amplified λ-DNA (amplicon size of 100 bp) within 10 min. Finally, we improved the qPCR efficiency by 2 cycle threshold (C_t) value compared with pristine PDMS reactor and quantified up to 10 copies/µL nucleic acids by fluorescence intensity enhancement resulting from light reflections property of TiO₂. By using TiO₂-PDMS nanocomposite-based PCR reactors, the fast and efficient nucleic acid assay was enabled without loss of sensitivity, and it can be practically used in the field of PoCT.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"240"},"PeriodicalIF":10.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNAzyme hydrogels specifically inhibit the NLRP3 pathway to prevent radiation-induced skin injury in mice.","authors":"Daijun Zhou, Zhihui Li, Linbo Bao, Xiang Zhao, Jie Hao, Chuan Xu, Feifan Sun, Dan He, Chaoyang Jiang, Tian Zeng, Dong Li","doi":"10.1186/s12951-025-03147-x","DOIUrl":"10.1186/s12951-025-03147-x","url":null,"abstract":"<p><p>Radiation-induced skin injury (RISI) is a frequent complication of radiotherapy, yet current preventive strategies exhibit suboptimal efficacy. Our previous publications have consistently demonstrated the effectiveness of biomaterials and hydrogels in preventing RISI. Based on comprehensive literature reviews, we speculate that NLRP3 overexpression plays a central role in the development of RISI. Therefore, designing DNAzyme (DZ)-hydrogels with targeted inhibition of NLRP3 overexpression is crucial for preventing RISI.To achieve this, we designed and screened the optimal NLRP3-DZ using bioinformatics, molecular dynamics, and gel electrophoresis methods. We encapsulated the NLRP3-DZ within ZIF-8 to enhance its stability, controlled release, and safety. To enhance the material's transdermal penetration and practicality, we attached the TAT transmembrane peptide. The final preparation and characterization of NLRP3-DZ@ZIF-8/TAT was achieved.In vitro cell models revealed that DZ-hydrogels exhibit high biosafety, effectively inhibit NLRP3 expression, promote cell migration, inhibit cell apoptosis, and possess antibacterial properties. Genomics analysis suggested that DZ-hydrogels may exert these functions by regulating changes in relevant mRNA pathways.Furthermore, we established a mouse model of RISI and found that the material can promote wound healing by regulating proteins associated with apoptosis, oxidative stress, and the inflammatory response. These research findings provide valuable insights for the prevention of RISI using DZ-hydrogels.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"238"},"PeriodicalIF":10.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microalgae-based biodegradable embolic agent for the treatment of hepatocellular carcinoma through transarterial embolization.","authors":"Kaiyue Wang, Danni Zhong, Lingxiao Yang, Cheng Zeng, Qitao Hu, Min Zhou, Zhe Tang","doi":"10.1186/s12951-025-03290-5","DOIUrl":"10.1186/s12951-025-03290-5","url":null,"abstract":"<p><p>Transarterial chemoembolization (TACE) serves as a locoregional therapy for hepatocellular carcinoma (HCC) patients. Nevertheless, the rapid dissociation of conventional TACE (cTACE) preparations, attributed to the instability of the emulsion, often leads to inadequate concentrations of chemotherapeutic agents within the tumor site. Consequently, there exists a pressing demand for an embolic agent that possesses facile injectability and the capacity to provide continuous delivery of chemotherapy drugs. Herein, we leveraged the inherent drug-loading capabilities and distinctive structural attributes of Spirulina platensis (SP) to formulate a novel microalgae embolic agent, doxorubicin loaded-Spirulina platensis (DOX-SP). The DOX-SP formulation exhibited a notable capacity for drug loading and demonstrated the ability to sustain drug release in response to acidic tumor microenvironments (TME). The spiral structure and micron-scale size of SP contributed to effective vascular embolization and continuous localized release of DOX. Furthermore, the biodegradability of SP as a natural biomaterial ensured good biosafety, with its degradation products potentially enhancing the pH of TME. In a rat model of in-situ hepatocellular carcinoma, DOX-SP effectively suppressed tumor growth and significantly reduced tumor size following intra-arterial injection, while exhibiting minimal adverse effects. Taken together, the high drug loading capacity, effective vascular embolization, pH sensitivity, TME pH modulation, and biodegradability of DOX-SP made it a promising embolic agent for hepatocellular carcinoma treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"234"},"PeriodicalIF":10.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diselenide-based nanoparticles enhancing the radioprotection to the small intestine of mice.","authors":"Yichi Huang, Jiaze Li, Sen Wang, Hongqi Tian, Saijun Fan, Yu Zhao","doi":"10.1186/s12951-025-03276-3","DOIUrl":"10.1186/s12951-025-03276-3","url":null,"abstract":"<p><p>The widespread application of ionizing radiation (IR) in medicine, while beneficial, also poses potential risks that necessitate effective countermeasures. Both 2-(3-aminopropylamino) ethanethiol (WR-1065) and curcumin are recognized as radioprotective agents; however, their clinical utility is hindered by notable shortcomings that could be addressed through reactive oxygen species (ROS)-responsive amphiphilic nanomaterials. We introduced a newly synthesized poly (ethylene glycol) (PEG)-polycaprolactone (PCL) polymer integrated with diselenide bonds and curcumin (HOOC-SeSe-Cur-PEG-SeSe-Cur-PCL, PEG-Cur-SeSe-PCL). The resulting spherical nanoparticles (NPs), which self-assembled from this polymer, were uniform with an average diameter of 118 nm. As a carrier for WR-1065, these NPs demonstrated a loading capacity of 30.9% and an efficacy of 56.7%. Importantly, the degradation of WR-1065 within the NPs was minimal in gastric fluid, decreasing by only approximately 20% over a 6-hour period. The innovative aspect of these NPs is their design to destabilize in ROS-rich environments, facilitating the release of WR-1065 and curcumin. Indeed, the survival rate of mice increased to 50% when these NPs were orally administered prior to exposure to a lethal dose of whole-body irradiation (8 Gy). The radioprotective impact of WR-1065-loaded NPs was evident in the small intestine of irradiated mice, characterized by the amelioration of radiation-induced epithelial damage, reduction of DNA damage, and inhibition of the apoptotic pathway. Collectively, this oral nanocarrier system for WR-1065 and curcumin holds promise as a potential candidate for the prophylaxis and treatment of acute intestinal injuries induced by IR.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"236"},"PeriodicalIF":10.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy-derived engineered stem cell exosomes improve anti-glioma immunotherapy by promoting the formation of tertiary lymphoid structure and improve the release of type I interferon.","authors":"Man Li, Lisen Lu, Qiuhong Bao, Minghui Zhou, Bin Nie, Yanchao Liu, Kai Shu, Ting Lei, Mingxin Zhu","doi":"10.1186/s12951-025-03301-5","DOIUrl":"10.1186/s12951-025-03301-5","url":null,"abstract":"<p><p>The absence of signaling pathways related to intrinsic immune activation in tumor cells and the immunosuppressive microenvironment limit lymphocyte infiltration, constitutes an \"immune-desert\" tumor displaying insensitivity to various immunotherapies. This study investigates strategies to activate intrinsic immune pathways in glioma cells, reverse immunosuppression, and induce tertiary lymphoid structures (TLS) within the glioma microenvironment (GME) to enhance natural and adaptive immune responses. We successfully induced antigen-presenting cell activation, macrophage/microglia polarization, and TLS formation in GME by intracranial delivery of BafA1@Rexo-SC, which comprises exosomes from irradiated bone marrow-derived stem cells overexpressing CD47 nanobodies and STING, loaded with the autophagy inhibitor BafA1. These exosomes efficiently activated the cGAS-STING pathway, leading to the formation of \"lymphoid tissue organizer cells (Lto)\" cells, VEGFA release for high endothelial microvessel formation, and chemokine release for T and B cell recruitment. BafA1@Rexo-SC also promoted macrophage phagocytosis of tumor cells and enhanced effector T cell function by blocking CD47, while releasing type I interferon. Our findings suggest novel therapeutic approaches for glioma treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"239"},"PeriodicalIF":10.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationally designed NIR-II excitable and endoplasmic reticulum-targeted molecular phototheranostics for imaging-guided enhanced photoimmunotherapy of triple-negative breast cancer.","authors":"Fen Liu, Qiang Kang, Hao Xiao, Yinying Liu, Sengyou Tan, Kun Fan, Jianchun Peng, Xiaofeng Tan, Guilong Wu, Qinglai Yang","doi":"10.1186/s12951-025-03282-5","DOIUrl":"10.1186/s12951-025-03282-5","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as a promising strategy for the treatment of TNBC. This approach works by selectively destroying tumor cells, releasing tumor-associated antigens, activating the immune system, and effectively inhibiting tumor proliferation and metastasis. However, the majority of current phototheranostic approaches are hindered by limited tissue penetration in the first near-infrared (NIR-I) and ultraviolet-visible (UV-Vis) regions. Additionally, due to the lack of specific subcellular targets, it may be difficult to effectively treat deep-seated lesions with ambiguous and extensive boundaries caused by TNBC metastases. Consequently, the development of effective, deep-penetrating, organelle-targeted phototheranostics is essential for enhancing treatment outcomes in TNBC. This work proposes a novel molecular design strategy of NIR-II phototheranostics to realize planar rigid conjugation and alkyl chain functionalization. The di-hexaalkyl chains in a vertical configuration on the donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) and shielding units (fluorene) are introduced to construct a S-D-A-D-S type NIR-II phototheranostics (IR-FCD). The planar and rigid structure of IR-FCD exhibits a robust intramolecular charge transfer capability, a lower band gap, enhanced photon absorption properties, and significant steric hindrance from vertically arranged alkyl chains to minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at the terminus of an elongated alkyl chain, followed by self-assembly into DSPE-S-S-PEG2000, NIR-II excitable phototheranostics (IR-FCD-Ts NPs) with endoplasmic reticulum (ER) targeting capability were successfully synthesized for imaging-guided photoimmunotherapy of TNBC. The IR-FCD-Ts NPs demonstrate exceptional optical characteristics, with maximum absorption at 1068 nm (extending to 1300 nm) and emission at 1273 nm (extending to 1700 nm), along with a high molar absorption coefficient of 2.76*10⁴ L/mol·c at 1064 nm in aqueous solution. Under exposure to 1064 nm laser irradiation, IR-FCD-Ts NPs exhibit superior photothermal properties and have the potential for photodynamic therapy. By targeting ER, thereby inducing ER stress and significantly enhancing immunogenic cell death (ICD) in tumor cells, it triggers a strong antitumor immune response and inhibits the proliferation and metastasis of TNBC.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"235"},"PeriodicalIF":10.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}