ACS nano medicinePub Date : 2026-01-08eCollection Date: 2026-04-08DOI: 10.1021/acsnanomed.5c00087
Fatma M Yurtsever, Martin Pumera
{"title":"Translational Application of Biomedical Microrobots in Female Reproductive System.","authors":"Fatma M Yurtsever, Martin Pumera","doi":"10.1021/acsnanomed.5c00087","DOIUrl":"10.1021/acsnanomed.5c00087","url":null,"abstract":"<p><p>Recent advancements in robotics enable the rapid evolution of micro/nanorobotic technologies which accelerates developing precise, patient-tailored diagnostic and therapeutic strategies. Untethered microrobots are making strides in the biomedical field due to their ability to access hard-to-reach locations in the organs, allow adjusting dosage time, and can be combined with different treatments. Potential impact is evident in women's health, where microrobotic systems may provide innovative solutions for gynecological cancers, fertility challenges, and bacterial infections within the female reproductive tract. In this perspective, we discuss the potential application of microrobots in the female reproductive system, actuation, fabrication methods, challenges, and future implications. Reproductive health is highly important for humanity's future; therefore, it is crucial to prioritize cutting-edge research in reproductive wellness.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 3","pages":"482-491"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2026-01-07eCollection Date: 2026-03-11DOI: 10.1021/acsnanomed.5c00114
Guojun Xiong, Alexandra Vaideanu, Ryan D Mellor, Chengwei Jiang, Benjamin Gardner, Nick Stone, Andreas G Schätzlein, Ijeoma F Uchegbu
{"title":"A Renally Excretable Gold Nanoparticle Oncology Platform Enabling Effective Photothermal Therapy and Chemotherapy Combination.","authors":"Guojun Xiong, Alexandra Vaideanu, Ryan D Mellor, Chengwei Jiang, Benjamin Gardner, Nick Stone, Andreas G Schätzlein, Ijeoma F Uchegbu","doi":"10.1021/acsnanomed.5c00114","DOIUrl":"10.1021/acsnanomed.5c00114","url":null,"abstract":"<p><p>Combination therapies have largely replaced monotherapies in oncology. Thermal therapy has been developed as an adjunctive treatment owing to its safety and high compatibility with established theraypy options. However, bulky equipment and non-standardized protocols have limited its clinical use. The emergence of gold nanoparticle (AuNP)-based photothermal therapy (PTT) offers a simpler approach using injectable formulations and portable near-infrared (NIR) laser devices. However, poor excretion of AuNPs raises safety concerns and hinders translation. Here, we designed a gold nanoplatform that retains the photothermal capacity of AuNPs while enabling efficient excretion. Ultrasmall AuNPs (<6 nm) with a hydrophilic coating may be renally cleared, but clustering normally alters biodistribution and results in long-term hepatic deposition, prior to excretion. In this study, we employed <i>p</i>-methoxybenzenethiol (MBT) to stabilize ultrasmall AuNPs, clustered them with poly-(lactic-<i>co</i>-glycolic acid) (PLGA), and coated said clusters with acetylated human serum albumin (Ac-HSA). The resulting Ac-HSA-PLGA-AuNCs demonstrated reduced hepatic retention along with renal excretion of ultrasmall gold species. Intratumoral injection followed by 10 min NIR irradiation achieved efficient tumor ablation, outperforming conventional hyperthermia that usually requires hours of heating. Furthermore, combining Ac-HSA-PLGA-AuNC-based PTT with high-dose paclitaxel (160 mg/kg) was safe and yielded enhanced antitumor efficacy. This developed gold nanoplatform offers a promising strategy for translatable PTT-chemotherapy combinations.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 2","pages":"466-481"},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-12-29DOI: 10.1021/acsnanomed.5c00129
Li Ma, Xinxin Zhang, Ke Cai, Jinhui Jiang, Zhongsheng Bi, Tao Tao, X. Li, Yue Yuan
{"title":"Enhanced PET/MRI Hybrid Imaging of Prostate Cancer with In Situ Self-Assembled <sup>68</sup> Ga/Gd Nanoplatform","authors":"Li Ma, Xinxin Zhang, Ke Cai, Jinhui Jiang, Zhongsheng Bi, Tao Tao, X. Li, Yue Yuan","doi":"10.1021/acsnanomed.5c00129","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00129","url":null,"abstract":"The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) presents a powerful tool for cancer diagnosis, yet the development of contrast agents that effectively enhances both modalities remains a challenge. Here, we introduce 68Ga/Gd-CBT-PSMA, a prostate-specific membrane antigen (PSMA)-specific probe designed for glutathione-induced intracellular coself-assembly in prostate cancer cells. This process drives the formation and accumulation of nanoparticles within the tumor, resulting in a concurrent amplification of both T1-weighted MRI and PET signals. This strategy achieves superior image contrast and resolution for precise tumor delineation, paving the way for improved diagnostic paradigms.","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 3","pages":"762-769"},"PeriodicalIF":0.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147903556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-12-18DOI: 10.1021/acsnanomed.5c00101
Tiantian Jiang, Zhen Chen, Anni Zhu, Ting Su, Jingchao Li
{"title":"A Self-Adjuvanting Nanovaccine with Ultrasound-Synchronized Activation for Coordinated Innate and Adaptive Antitumor Immunity","authors":"Tiantian Jiang, Zhen Chen, Anni Zhu, Ting Su, Jingchao Li","doi":"10.1021/acsnanomed.5c00101","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00101","url":null,"abstract":"Immunotherapy has demonstrated considerable potential in cancer treatment; however, it continues to face persistent challenges such as tumor heterogeneity, immunosuppressive microenvironments, and inefficient delivery of immunomodulators. To overcome these limitations, we develop a self-adjuvanting nanovaccine (NVMP) that incorporates the following key components: (1) covalent conjugation of the STING agonist MSA-2 to a model neoantigen, (2) a semiconducting polymer (PF8DPP) for sonodynamic therapy, and (3) a reactive oxygen species (ROS)-responsive nanoparticle shell. With ultrasound (US) irradiation, PF8DPP produces ROS, which induces localized immunogenic cell death (ICD) and cleaves the ROS-responsive shell to promote the intratumoral release of antigen-adjuvant conjugates. The covalent linkage between the antigen and adjuvant ensures the synchronous uptake and activation within antigen-presenting cells (APCs), followed by glutathione (GSH)-mediated release of MSA-2. This strategy enables dual-pathway immune activation via combining STING agonism with ICD-derived damage-associated molecular patterns (DAMPs). In B16-OVA melanoma models, NVMP exhibits superior therapeutic efficacy, significantly suppressing primary tumor growth and eliciting robust systemic immunity that effectively inhibits metastasis. The spatially confined, US-triggered activation mechanism will minimize off-target toxicity. Thus, NVMP represents a paradigm-shifting platform that facilitates coordinated codelivery of antigen and adjuvant, STING activation, and US-enhanced remodeling of the tumor microenvironment for cancer therapy.","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 3","pages":"737-752"},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147902912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypersensitive PTT Mediated with a Capsaicin-Participant Fever-Like Temperature to Promote CD8 <sup>+</sup> T cells Expansion for Enhanced Antitumor Immunity","authors":"Ying Zhang, Shengnan Wang, Mingyu Ding, Qiong Li, Pengfei Shi, Shusheng Zhang","doi":"10.1021/acsnanomed.5c00079","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00079","url":null,"abstract":"","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 3","pages":"678-692"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147913050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-11-22eCollection Date: 2026-02-11DOI: 10.1021/acsnanomed.5c00059
Eric H Sterin, George C Kramarenko, Chitran Roy Chowdhury, Sriram Pramod Tendulkar, Kejian Li, Timothy Chaya, Jenna Muscat-Rivera, Jilian R Melamed, Emily S Day
{"title":"Exogenous CD55 Expression on Membrane-Wrapped Nanoparticles Unexpectedly Increases Spleen Tropism and Immune Cell Uptake <i>In Vivo</i>.","authors":"Eric H Sterin, George C Kramarenko, Chitran Roy Chowdhury, Sriram Pramod Tendulkar, Kejian Li, Timothy Chaya, Jenna Muscat-Rivera, Jilian R Melamed, Emily S Day","doi":"10.1021/acsnanomed.5c00059","DOIUrl":"10.1021/acsnanomed.5c00059","url":null,"abstract":"<p><p>Intravenously delivered nanoparticle (NP) therapies have the potential to cure a variety of diseases; however, their clinical use has been stunted by undesirable levels of immune cell clearance. This clearance is attributed to protein adsorption onto the outside of the NPs, leading to recognition by immune cells and subsequent accumulation in the liver and spleen. Membrane-wrapped nanoparticles (MWNPs) offer a potential solution to reducing immune clearance by incorporating immune evasion/marker-of-self-proteins, although they too exhibit protein corona-mediated clearance. While various opsonin proteins can bind to MWNPs, complement proteins are particularly problematic as they play a crucial role in innate immunity, triggering immune cell recognition and clearance and causing inflammation. We hypothesized that introducing a complement regulatory protein into the membranes of MWNPs could minimize complement-mediated clearance, but the opposite effect was observed experimentally. In this study, before membrane collection, source cells were genetically modified to express the complement regulatory protein, CD55, which inhibits C3 convertases, key enzymes in the complement cascade. We confirmed that the active protein was transferred onto MWNPs and determined that CD55-modified MWNPs incubated in mouse serum significantly reduced C3 convertase concentration by 33% compared to unmodified MWNPs. Unexpectedly, <i>in vivo</i> analysis of biodistribution and immune cell uptake showed that CD55-modified MWNPs exhibited 2.1× higher spleen accumulation and elevated immune cell uptake in blood and spleen, specifically in monocyte/macrophage populations, as compared to unmodified MWNPs. This may be due to nonprotein corona-mediated mechanisms, such as the secondary role of CD55 as a ligand for CD97 (expressed in monocytes, macrophages, and other immune cells). Supporting this theory, studies examining <i>ex vivo</i> MWNP binding to spleen cells pretreated with IgG or CD97 antibodies showed that CD55-modified MWNPs had 18% lower binding after CD97 blockade, whereas unmodified MWNP binding was not reduced by CD97 blockade. These findings highlight the importance of considering both serum protein interactions and ligand/receptor interactions when designing genetically engineered MWNPs that overexpress a protein of interest, as well as the importance of testing modified MWNPs in both <i>ex vivo</i> and <i>in vivo</i> settings. In the future, the CD55 modification described here could be utilized to promote spleen tropism of MWNPs when desired. More broadly, this work demonstrates the ability to tune MWNP cellular interactions and biodistribution through genetic engineering of source cellsa technique that can be adapted for a plethora of uses in precision medicine.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 1","pages":"283-296"},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-11-14DOI: 10.1021/acsnanomed.5c00070
Seraphim Kozlov, Martin Panigaj, Laura Rebolledo, Hari Bhaskaran, Kirill A Afonin
{"title":"Nucleic Acid Nanoparticles Redefine Traditional Regulatory Terminology: The Blurred Line between Active Pharmaceutical Ingredients and Excipients.","authors":"Seraphim Kozlov, Martin Panigaj, Laura Rebolledo, Hari Bhaskaran, Kirill A Afonin","doi":"10.1021/acsnanomed.5c00070","DOIUrl":"10.1021/acsnanomed.5c00070","url":null,"abstract":"<p><p>Nucleic acid nanoparticles (NANPs) make up a structurally heterogeneous class of nanosized architectures that self-assemble from rationally designed oligonucleotides via canonical and noncanonical base-pairing. Over the past decade, extensive research and development have advanced NANP technologies, bringing them closer to clinical settings. Notably, several functional nucleic acid components, integral to NANPs, have already received regulatory approval for therapeutic use. The successful translation of NANPs requires a comprehensive understanding of not only their key quality attributes but also the definitions established by regulatory health agencies, as such classification helps apply an appropriate regulatory framework to ensure successful clinical translation. A critical analysis of current knowledge about NANPs in the context of regulatory definitions reveals that NANPs can serve as active pharmaceutical ingredients (APIs) and excipients and can even combine both functions simultaneously, depending on their intended therapeutic mechanism of action and formulation context. This dual-role capacity is relatively unique among pharmaceutical materials, as most current materials serve as either an API or an excipient. Moreover, the potential for conditional activation of therapeutic functions for NANPs designed to become biologically active only in specific physiological environments adds a further layer of complexity to their regulatory classification.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-10-31DOI: 10.1021/acsnanomed.5c00061
Rongrong Zheng, Xia‐Yun Chen, S W Zhang, Yixin Liu, Qiuyuan Li, Xin Chen, Tao Wang, Ling‐Wen Ding, Linping Zhao, Shiying Li
{"title":"A Ferroptosis Amplification Loop Induced by Compensatory Nanomedicine Enhances Breast Cancer Immunotherapy","authors":"Rongrong Zheng, Xia‐Yun Chen, S W Zhang, Yixin Liu, Qiuyuan Li, Xin Chen, Tao Wang, Ling‐Wen Ding, Linping Zhao, Shiying Li","doi":"10.1021/acsnanomed.5c00061","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00061","url":null,"abstract":"Tumor cells often develop compensatory mechanisms to evade antitumor therapies, thereby diminishing therapeutic efficacy. In this work, a self-delivering compensatory nanomedicine (designated as a BRC) is developed to amplify ferroptotic cell death and potentiate αPD-L1 therapy in breast cancer. By optimizing intermolecular interactions, the dihydroorotate dehydrogenase (DHODH) inhibitor brequinar (Bre), the ferroptosis inducer RSL3, and the photosensitizer chlorin e6 (Ce6) are coassembled into a uniform and stable nanostructure without the need for additional carriers. Upon light activation, BRC initiates photodynamic therapy (PDT)-induced lipid peroxidation, which synergizes with GPX4 inhibition and disruption of the DHODH-mediated compensatory pathway, thereby establishing a ferroptosis-amplifying loop that triggers potent ferroptotic cell death. As a result, BRC not only suppresses primary tumor growth but also significantly enhances tumor immunogenicity. Moreover, in combination with the αPD-L1 blockade, BRC effectively activates both innate and adaptive immune responses, resulting in the eradication of metastatic tumors without observable systemic toxicity. This work presents a compelling strategy that targets compensatory resistance mechanisms to induce ferroptotic cell death, offering a promising approach to potentiating breast cancer immunotherapy.","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147331157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ACS nano medicinePub Date : 2025-10-16eCollection Date: 2026-02-11DOI: 10.1021/acsnanomed.5c00053
Tiffany Ho, Michael Valic, Tracy W Liu, Mark Zheng, Yiming Yang, Keegan Guidolin, Lili Ding, Yulin Mo, Ashley Qian, Nahyun Kwon, Layla Pires, Brian C Wilson, Ali Makky, Juan Chen, Gang Zheng
{"title":"A Membrane Fluidization Strategy Significantly Boosts Photodynamic Therapy and Antitumor Immunity of Porphyrin-Lipid Nanoparticles.","authors":"Tiffany Ho, Michael Valic, Tracy W Liu, Mark Zheng, Yiming Yang, Keegan Guidolin, Lili Ding, Yulin Mo, Ashley Qian, Nahyun Kwon, Layla Pires, Brian C Wilson, Ali Makky, Juan Chen, Gang Zheng","doi":"10.1021/acsnanomed.5c00053","DOIUrl":"10.1021/acsnanomed.5c00053","url":null,"abstract":"<p><p>Porphysomes (PS) are self-assembled porphyrin-lipid nanoparticles with intrinsic multifunctionality for cancer theranostics. We recently discovered that incorporating EDTA-conjugated lipids (EDTA-lipids) into lipid nanoparticle formulations significantly enhances intracellular uptake by modulating the cell membrane fluidity. To retain the favorable <i>in vivo</i> properties of PS while improving intracellular porphyrin delivery for effective photodynamic therapy (PDT), we developed a dual cellular- and vascular-enriched porphysome (DE-PS) containing 30 mol % cholesterol, 5 mol % PEG2000-DSPE, 27 mol % pyro-lipid, and 38 mol % EDTA-lipid. DE-PS demonstrated favorable pharmacokinetics (<i>t</i> <sub><sub>1</sub>/<sub>2</sub>β</sub> = 7.5 h), robust photostability (>99% fluorescence quenching), and strong serum stability over 24 h (>85% fluorescence quenching retained). Compared to PS, DE-PS resulted in an 11-fold increase in KB cancer cell uptake and achieved >95% PDT-induced cell death, in contrast to <5% with PS. Intravital imaging showed enhanced intratumoral porphyrin activation in DE-PS-treated mice, with stronger fluorescence signals observed in tumor vasculature and necrotic regions, leading to superior <i>in vivo</i> PDT efficacy across all drug-light-intervals. Notably, while low-dose PDT (25 J/cm<sup>2</sup>) with DE-PS had minimal impact on CT-26 tumor growth in immunodeficient NSG mice, it resulted in marked tumor suppression and prolonged survival in immunocompetent BALB/c mice, highlighting the importance of PDT-induced immune activation in the therapeutic response. A single DE-PS PDT treatment led to durable tumor-free survival exceeding 90 days. Upon CT-26 tumor rechallenge, previously cured mice rejected tumor regrowth, demonstrating development of long-lasting immunity without utilizing additional immunostimulants. This study highlights DE-PS as a promising next-generation porphysome-based photosensitizer platform for effective cancer phototherapy and immune modulation.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 1","pages":"268-282"},"PeriodicalIF":0.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}