Purpose:Ultra-sensitive detection of exosomal miR-21 is crucial for the early diagnosis of colorectal cancer. This study aims to develop a cascade amplification platform based on surface-enhanced Raman scattering (SERS), combining rolling circle amplification (RCA) and CRISPR/Cas12a, to enable ultra-sensitive quantitative detection of exosomal miR-21. Methods:A SERS substrate was constructed using streptavidin-modified concave gold nanocubes (CGNs), and gold double-stranded probes loaded with Raman reporter molecules were used as SERS probes. The two components are controllably linked via a single-stranded DNA molecule with a thiol group at one end and biotin at the other, forming a stable detection system. Target-triggered RCA generates a repeat sequence, which, under the mediation of crRNA, activates Cas12a cleavage, causing the probe to be released from the substrate surface and resulting in a significant attenuation of the SERS signal. Results:This platform achieves three-stage cascading signal amplification via RCA, CRISPR/Cas12a, and SERS, with a detection limit at the femto-mole (fM) level and a total detection time of approximately 80 minutes. The results were consistent with those of qRT-PCR, demonstrating high sensitivity, high specificity, and reliability. Conclusion:This study proposes an RCA-CRISPR-SERS cascade amplification platform that provides a highly sensitive and specific method for detecting miR-21 in exosomes, offering potential clinical value for the early diagnosis and dynamic monitoring of colorectal cancer.
Pulmonary arterial hypertension (PAH) is a cardiovascular disease characterized by a hidden or insidious onset with symptoms including dyspnea and heart failure, which can result in sudden death. Inflammation and oxidative stress are key factors in the pathogenesis of PAH. Hence, anti-inflammatory and antioxidant agents are promoted as therapeutically beneficial. However, the efficacy and safety of these therapeutics are limited by poor solubility and stability, short half-life, lack of targeting capability, and significant side effects. The pulmonary vasculature of patients with PAH exhibits highly heterogeneous blood flow distribution, characterized by reduced wall shear stress and vortex formation at pulmonary artery bifurcations. Abnormal shear stress impairs endothelial function and induces progressive pulmonary vascular remodeling. Combined with endothelial barrier dysfunction, these hemodynamic alterations collectively govern the adhesion, retention and transmural transport of nanocarriers within diseased blood vessels. Nanocarriers (NCs) including liposomes, polymeric and exosomes, through intelligent responsiveness, combination therapy, and personalized and precision delivery strategies, can significantly enhance drug stability, prolong half-life, achieve specific targeting of pulmonary lesions, and reduce side effects. In addition, local administration methods, such as aerosol inhalation and intratracheal instillation, can achieve efficient drug accumulation in the lungs, thereby reducing systemic toxicity. This review summarizes the latest advances in the application of NCs to deliver anti-inflammatory and antioxidant agents for the treatment of PAH, and sorts out multiple translational bottlenecks identified in preclinical investigations. These critical challenges include rapid pulmonary clearance of inhaled nanoformulations, unclear long-term safety after repeated administration, low scalable production yield of nanocarriers, poor storage stability of preparations, inconsistent drug encapsulation efficiency, and unclarified in vivo action mechanisms. It provides solid theoretical support to address the above translational hurdles and advance precision clinical therapy for PAH.
Purpose:The main purpose of the present study was to explore chitosan as a polymeric material for the preparation of vonoprazan nanoparticles intended for use as a delivery system for acid-related diseases. Methods:Vonoprazan-loaded chitosan nanoparticles were formulated using the ionotropic gelation method and characterized in terms of size, zeta potential, polydispersity index, drug entrapment efficiency (EE), FTIR, XRD, Thermal analysis, SEM, in vitro release study at two different pH levels, and drug release kinetics. Acute oral toxicity was assessed to evaluate safety and pharmacokinetic studies were performed to determine bioavailability. Results:The optimized formulation VCHNP4 demonstrated a mean particle size of 496.5±1.19 nm, a zeta potential of 25.4±3.07 mV, a polydispersity index of 0.474±1.97, and an entrapment efficiency of 78.09±0.41. Surface morphology studies revealed a spherical shape with inclusions of drug-loaded chitosan nanoparticles. Thermal stability was improved, as observed by thermal analysis, and PXRD confirmed the amorphous state of the drug. Saturation solubility testing indicated significantly enhanced solubility of the drug and exhibited pH-dependent drug release, with higher release at pH 1.2 compared to pH 6.8, following the Korsmeyer-Peppas model. Acute oral toxicity studies showed no major differences in the clinical parameters between the control and treatment groups. In vivo pharmacokinetics showed that VCHNPs achieved superior Cmax (307 ± 0.61 ng/mL) compared to VPZ (41 ± 1.01 ng/mL) (p < 0.05). Conclusions:This study showed that mucoadhesive polymeric nanoparticles of vonoprazan significantly enhanced solubility, pH-dependent release, and improved mucoadhesion, making it a promising approach to improve the oral bioavailability of drugs with poor water solubility.
Self-assembled nanosystems based on non-covalent interactions of traditional Chinese medicine (TCM) monomers have attracted extensive attention in drug delivery. In direct carrier-free systems, the active molecules also serve as building units. These systems may reduce the need for extra carriers and provide high drug loading. Hybrid systems may instead depend on polymers, ions, membranes, or other added materials. This review follows a molecular structure-assembly-property-function chain. Molecular features and environmental conditions guide the assembly pathway. The pathway produces structures such as nanoparticles, fibers, ribbons, and hydrogels. These structures have different sizes, shapes, surface properties, stability, mechanical properties, and responses. These properties can then affect drug release, cellular uptake, tissue retention, targeting, and treatment outcomes. Co-assembly adds another level of control. Component identity and component ratio can change molecular interactions, morphology, and function. The review separates control shown under tested conditions from full programmable design. Most reported systems are controllable only under tested conditions. Few studies have reached full programmable design. This review summarizes molecular rules, control factors, co-assembly modes, and characterization methods. It also discusses applications in druggability, disease treatment, targeted delivery, tissue repair, and theranostics. The review compares direct monomer assembly with polymer-, ion-, membrane-, and carrier-assisted systems. It also discusses reproducibility, biological stability, safety, scale-up, and regulation. The review aims to support more reproducible and predictable design of TCM-derived nanomedicines.
Weranga Rajapaksha,1 Preethi Eldi,1 Todd A Gillam,1,2 Anton Blencowe,3 Sanjay Garg,1 Hugo Albrecht,1 Riya Khetan11Centre for Pharmaceutical Innovation (CPI), School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, SA, Australia; 2Whimsical Interdisciplinary Laboratory of Discovery (WILD) Research Group, School of Mathematics, Statistics, Chemistry and Physics, Murdoch University, Murdoch, Western Australia, Australia; 3Applied Chemistry and Translational Biomaterials (ACTB) Group, Centre for Pharmaceutical Innovation (CPI), School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, SA, AustraliaCorrespondence: Hugo Albrecht, Centre for Pharmaceutical Innovation (CPI), School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, SA, Australia, Email hugo.albrecht@adelaide.edu.au Riya Khetan, Centre for Pharmaceutical Innovation (CPI), School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, SA, Australia, Email riya.khetan@adelaide.edu.auAbstract: Ovarian cancer remains highly lethal due to late diagnosis, frequent recurrence, and rapid development of resistance to platinum-based chemotherapy. Although rational drug combinations targeting multiple oncogenic pathways hold promise, their clinical utility is often compromised by dose-limiting toxicity and tumor heterogeneity. Antibody-drug conjugates (ADCs) offer an alternative by delivering potent agents directly to tumor cells, thereby reducing systemic toxicity. This approach could be further enhanced by the dual targeting of co-expressed tumor-specific cell surface receptor pairs to broaden tumor coverage and enable the precise delivery of synergistically active drugs. Furthermore, nanotechnology-based carriers extend these concepts by enabling the integration of multiple targeting ligands and payloads into a single drug-delivery platform. Systematic identification and validation of novel co-targeting cell surface receptors, such as G protein-coupled receptors (GPCRs), characterized by high tumor relevance and rapid internalization, may improve tumor coverage and drug uptake in therapy-resistant subpopulations. The outlined strategies are very promising to advance precise and personalized treatment strategies for ovarian cancer. However, dual-receptor approaches remain largely investigational, with limited preclinical validation, and their clinical translation is challenged by receptor heterogeneity, uncertain tumor selectivity, potential off-target effects, and inefficient delivery due to tumor-microenvironment barriers. Furthermore, manufacturing, safety, and regulatory requirements need to be addressed.Keywords: dual targeting, ovarian cancer, nanomedicine, active targeting, precision therapy
Mengyue Yang, Jinhui WuCenter of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jinhui Wu, Email wujinhui@scu.edu.cnAbstract: Pathological cardiac hypertrophy is a major contributor to heart failure and is characterized by complex molecular mechanisms involving transcriptional and epigenetic regulation, signal transduction, metabolic remodeling, inflammatory responses, and extracellular matrix remodeling. Although conventional pharmaceutical treatments may alleviate the progression of cardiac hypertrophy, their clinical effectiveness is limited by poor cardiac selectivity, systemic side effects, and limited efficacy in reverseing pathological remodeling. Recently, nanoparticle-based strategies have emerged as a promising therapeutic approach for cardiac hypertrophy owing to their ability to enhance cardiac-targeted drug delivery, enable controlled or stimuli-responsive drug release, and reduce off-target toxicity through improved biodistribution. This review systematically summarizes the design strategies of nanoparticle-based therapies for pathological cardiac hypertrophy, including material platforms such as inorganic, organic, and biomimetic nanoparticles, key delivery strategies such as passive targeting, active targeting, biomimetic targeting, and stimulus-responsive release, and administration routes including intravenous, intraperitoneal, intradermal, inhalation, and oral administration. In addition, this review provides a comprehensive summary of the preclinical applications of the above strategies in the fields of gene and epigenetic regulation, antioxidant, anti-inflammatory, and anti-fibrotic treatments. Finally, this review analyzes the challenges in clinical translation on the basis of critical issues, including long-term biosafety, insufficient targeting efficacy, large-scale production, and appropriate administration routes.Keywords: pathological cardiac hypertrophy, nanomedicine, targeted drug delivery, stimuli-responsive release, precision therapy
Junfeng Ban,1– 3 Yichao Li,1– 3,* Yanhua Guo,4,* Huashen He,1– 3 Chuangzan Yang,1,2 Peining Li,4 Jiawei Liang,1,2 Shirui Li,1,2 Xueyuan Luo,1,2 Yu Li,1,2 Yi Xie,1,2 Xiangmei Liu,4 Xiaofang Li1,21School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Engineering Research Center of Small Molecule Drugs, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Pharmaceutical Preparations Research and Evaluation, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 4Department of New Materials and Passive Medical Device Inspection and Research, Guangzhou Institute of Quality Inspection, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangmei Liu; Xiaofang Li, Email 283830090@qq.com; lixiaofang105@163.comBackground: Rapid local drug clearance and poor sustained retention pose challenges to the treatment of osteoarthritis. Therefore, a local delivery system that prolongs intra-articular drug retention and achieves efficient targeted delivery holds significant clinical promise.Methods: Hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-Cxb-NLCs) were prepared and encapsulated in dissolving microneedles to form a composite delivery system (HA-Cxb-NLCs-DMNs). The system was characterised in terms of its physicochemical properties, in vitro drug release profiles, transdermal permeation behaviour, cellular compatibility, and uptake mechanisms. Subsequently, a sodium iodoacetate-induced rat osteoarthritis model was used to evaluate the therapeutic efficacy in vivo.Results: HA-Cxb-NLCs-DMNs exhibit a uniform particle size (113.93 ± 1.66 nm) and a zeta potential of (− 39.16 ± 3.00 mV). In vitro release persisted for 72 hours, with a cumulative permeation of 62.74 ± 1.40 μg·cm− 2 and a skin retention of 3.20 ± 0.62 μg·cm− 2. HA modification enhances cellular uptake of the nanocarriers via the CD44 receptor. Animal studies demonstrated that it reduces joint swelling, improves cartilage damage, and inhibits MMP-13 expression.Conclusion: This study presents a promising microneedle-nanoparticle synergistic delivery strategy for the local targeted therapy of osteoarthritis.Keywords: dissolving microneedles, hyaluronic acid-modified celecoxib nanolipid carrier, osteoarthritis, transdermal administration
Jing Zhang,1,2 Xiaoqiang Kong,1 Xiangping Wu,1 Dongyun Tao,1 Xiang Li,1 Huimin Cheng11Key Laboratory of Modern Preparation of TCM, Ministry of Education, National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 2China Resources Jiangzhong Pharmaceutical Group Co., Ltd., Nanchang, Jiangxi, 330096, People’s Republic of ChinaCorrespondence: Xiang Li, Email xiang.li@jxutcm.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor prognosis, and Fusobacterium nucleatum (Fn) colonization further aggravates tumor progression, immunosuppression and therapeutic resistance. Conventional monotherapies are limited by insufficient tumor targeting, rapid drug clearance and failure to reverse immune suppression. Here, we fabricated cRGD-modified nanoparticles (Ag@GQDs/QUE-siP-c-L) for co-delivery of AgNPs, quercetin (QUE) and PD-L1 siRNA (siP).Methods: The morphology, particle size, surface metal elements, drug content and QUE entrapment efficiency of Ag@GQDs/QUE-siP-c-L were obtained using particle size analysis, SEM, inductively coupled plasma-optical emission spectrometry (ICP-OES) and HPLC. We further detected cellular uptake, in vitro drug release, cytotoxicity, intracellular reactive oxygen species level, PD-L1 gene silencing efficiency and in vitro anti-Fn activity. Pharmacokinetics and tissue distribution of Ag and QUE were analyzed by ICP-OES and LC-MS/MS, and in vivo antitumor efficacy and biosafety were tested in Fn-colonized orthotopic 4T1 tumor mice.Results: Ag@GQDs/QUE-siP-c-L exhibited uniform spherical morphology (195.87± 15.96 nm) with high encapsulation of QUE. cRGD modification enhanced Ag/QUE cellular uptake in 4T1 cells, with pH-responsive release accelerated under tumor acidic conditions. The nanoparticles exhibited selective tumor cytotoxicity, induced oxidative stress, downregulated PD-L1 mRNA, and exerted potent anti-Fn activity in vitro. Pharmacokinetics revealed increased AUC0-t and reduced clearance compared with free drugs, and cRGD modification promoted tumor accumulation and retention of drugs. In vivo preliminary experiments proved the Ag@GQDs/QUE-siP-c-L formulation suppressed tumor growth with a tumor inhibition rate of 45%, and effectively modulated the tumor immune microenvironment: it increased tumor-infiltrating CD3⁺CD4⁺ T cells, reduced PD-L1⁺CD11c⁺ dendritic cells, and decreased the proportions of immunosuppressive Tregs and MDSCs. Hematoxylin-eosin staining and serum liver-kidney biochemistry confirmed no obvious systemic toxicity.Conclusion: Ag@GQDs/QUE-siP-c-L serves as a multimodal nanoplatform for Fn-associated TNBC with combined in vitro antibacterial, gene silencing and in vivo antitumor immunomodulatory effects, showing great potential for future translational research.Keywords: silver nanoparticles, PD-L1 siRNA, Fusobacterium nucleatum, breast cancer, quercetin, combined therapy
Jingwen Tang,1 Mengnan Liu,1 Ruizhi Zhang,1 Qiang Li,1 Shengtao Wang,2 Yuehua Wang11Department of General Surgery, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Yuehua Wang, Department of General Surgery, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, People’s Republic of China, Email wangyuehua0812@163.com Shengtao Wang, School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Email 1107426546@qq.comAbstract: Colorectal cancer (CRC) remains a major global health burden, with limited efficacy of conventional treatments due to tumor heterogeneity, drug resistance, and systemic toxicity. Lipid metabolism reprogramming has emerged as a hallmark of CRC progression, influencing tumor growth, metastasis, and therapy resistance. Concurrently, nanomedicine offers innovative platforms for targeted drug delivery to to inhibit tumor progression by intervening in the lipid metabolism, including modulation of lipid synthesis, uptake, storage, and cholesterol metabolism. This review provides an integrated perspective, systematically summarizing therapeutic strategies and research progress on nanodrugs targeting lipid metabolic reprogramming in CRC. We highlight nanoplatforms engineered to deliver inhibitors of key enzymes and signaling pathways, such as PI3K/AKT and Wnt/β-catenin. Representative nanoplatforms are discussed to illustrate diverse strategies for regulating lipid metabolic vulnerabilities in CRC, such as carrier-free nanoparticles, RBC membrane-coated nanocages and cholesterol-responsive nanoparticles. We also discuss the challenges in clinical translation, including tumor heterogeneity, biosafety, large-scale production, and clinical validation. Furthermore, we provide insight into translational challenges, emerging trends, and future directions for integrating lipid-targeted nanotherapies into clinical practice.Keywords: CRC treatment, nanoparticle, abnormal lipid metabolism, signaling pathway, precision nanomedicine
Yao Wang,1,* Meng Lin,1,* Qi Sun,2 Tianfei Fan,1 Minglu Zhou,1 Wei Yang,1 Ting Zhang11Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical university, Beijing, 100069, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Zhang, Email zhangtingyx@yeah.netAbstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a high disability rate. Its core pathogenesis involves immune dysregulation, characterized notably by the aberrant polarization of macrophages toward the pro-inflammatory M1 phenotype, along with the abnormal proliferation and invasion of fibroblast-like synoviocytes. These interrelated processes collectively contribute to progressive joint destruction. Although traditional drug therapies can alleviate symptoms, they are frequently accompanied by significant side effects and fail to achieve curative outcome. In this context, smart polymer nanoparticles (SPNs) have emerged as a promising platform for rheumatoid arthritis therapy, offering multifunctional capabilities. Here, we provide a comprehensive and timely analysis of the multifaceted therapeutic applications of SPNs in RA. By delivering immunomodulatory agents, smart polymer nanoparticles can rebalance macrophage polarization, promoting M1-to-M2 conversion. Moreover, they effectively suppress the pathological activation of fibroblasts, thereby inhibiting synovial proliferation and bone invasion. Furthermore, these nanoparticles can also disrupt the vicious cycle of disease progression by ameliorating metabolic dysregulation within the joint microenvironment. The challenges for the clinical translation of SPNs in RA therapy are discussed and the possible solutions are proposed. Collectively, SPNs fundamentally intervene in RA pathogenesis through precise targeting and intelligent drug release, enabling a highly effective and low-toxicity strategy.Keywords: smart polymer nanoparticles, rheumatoid arthritis, macrophages, fibroblasts, microenvironment
Guoqing Liu,1 Meirong Li,1 Jiayu Liu,1 Yi-Ping Li,1 Xin Huang,1 Xu Guo,2 Qingfeng Zhai,1 Fengxiang Zhang,1 Wenjing Yan,1 Jinyue Sun1,21School of Public Health, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Wenjing Yan, Email wjyan@sdsmu.edu.cn Jinyue Sun, Email moon_s731@hotmail.comAbstract: Small extracellular vesicles (sEVs) are endogenous lipid-bilayer nanovesicles that combine cargo protection, biological membrane compatibility, and modifiable surface recognition. For colon-targeted delivery, their value depends on engineering them to withstand gastric acidity and proteolysis, negotiate the mucus barrier, and respond to colon-specific cues, including the distal gastrointestinal pH profile, microbiota-derived enzymes, inflammatory reactive oxygen species, and lesion-associated receptors such as integrins, CD44, and folate receptors. This review critically compares sEVs with conventional colon-targeted drug delivery systems and summarizes sEV biogenesis, cargo sorting, isolation, characterization, exogenous and endogenous loading, surface engineering, and passive, active, and stimuli-responsive targeting strategies. Therapeutic applications are evaluated in inflammatory bowel disease and colorectal cancer, with attention to epithelial barrier restoration, immune regulation, macrophage polarization, apoptosis, tumor-microenvironment remodeling, and emerging intestinal indications such as irritable bowel syndrome. Recent clinical trials, Good Manufacturing Practice requirements, potency and release specifications, safety assessment, and regulatory uncertainties are also discussed. A disease- and route-oriented decision framework is proposed to connect cargo properties, administration route, target-cell biology, manufacturing feasibility, and clinically meaningful endpoints. Although engineered sEVs remain investigational and no therapeutic product has achieved full regulatory approval, integration of microfluidic manufacturing, organ-on-chip validation, artificial intelligence-assisted design, and image-guided precision delivery may improve reproducibility and translational readiness.Keywords: small extracellular vesicles, sEVs, colon-targeted delivery, inflammatory bowel disease, IBD, colorectal cancer, CRC, irritable bowel syndrome, IBS, engineering strategies
Anni Wang,1 Yizhuo Huo,1 Yunxian Wu,1 Yuze Cheng,1 Yuchen Luo,1 Wenying Song,1 Junyang Chen,1 Lei Fu,1 Tao Lu1,21Wisdom Lake Academy of Pharmacy, Xi’an Jiaotong-Liverpool University, Suzhou, People’s Republic of China; 2Jiangsu Province Higher Education Key Laboratory of Cell Therapy Nanoformulation (Construction), Xi’an Jiaotong-Liverpool University, Suzhou, People’s Republic of ChinaCorrespondence: Tao Lu, Email Tao.Lu@xjtlu.edu.cnBackground: Activated hepatic stellate cells (HSCs) are key drivers of liver fibrosis, which progresses irreversibly without effective intervention. The natural alkaloid berberine (BBR) has been reported to possess anti-fibrotic activity. However, the poor solubility and injection-associated systemic toxicity of free BBR confine it to oral administration, resulting in its low bioavailability. Nanocarrier encapsulation addresses these drawbacks, and we therefore aimed to develop an HSC‑preferential delivery system with loaded BBR to improve its anti-fibrosis effects without causing systemic toxicity.Methods: In this study, vitamin A-modified lipids were synthesized to fabricate HSC‑preferential liposomes to encapsulate BBR and enhance delivery efficiency. This targeted BBR liposomal system was physiochemically characterized, followed by in vitro assessments of cellular uptake and inhibition of HSCs activation. In vivo animal studies were performed to validate the therapeutic efficacy of targeted BBR liposomes against hepatic fibrosis.Results: VA-modified BBR liposomes had an average size of 165.9 ± 7.1 nm with the desired size distribution. Compared to untargeted BBR liposomes, VA-modified liposomal BBR showed significantly increased HSC uptake, thus indicating enhanced inhibition of HSC activation by dramatically reducing HSC migration and proliferation abilities and decreased collagen1 expression in vitro. Intriguingly, contrary to earlier literature, we detected elevated α‑SMA expression upon BBR treatment despite the suppression of cell migration, proliferation and collagen production. In hepatic fibrosis mouse models, targeted BBR liposomes at 5 mg/kg significantly decreased aspartate aminotransferase and alanine aminotransferase levels in serum, and markedly reduced fibrotic areas and collagen synthesis and deposition, while equal doses of untargeted BBR liposomes showed negligible effects.Conclusion: Our results demonstrate that VA-functionalized liposomes facilitate the efficient targeted delivery of BBR to activated HSCs in hepatic fibrosis. Such targeted delivery augments the inherent anti-fibrotic potency of free BBR, highlighting the potential of this nanoplatform for hepatic fibrosis treatment.Keywords: cell-specific delivery, lipid based nanocarrier, vitamin A acid, berberine, liver fibrosis
Zhikui Huo,1,* Qianchuang Sun,2,* Jinbao Xiao,3 Weijie Zhu,1 Haibo Yang,1 Jiannan Li11Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Operating Theater and Anesthesiology, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Pharmacy, The Second Hospital of Jilin University, Changchun, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiannan Li, Email jnli@jlu.edu.cnAbstract: Platelet lysate (PL), enriched with growth factors, cytokines, and proteins, exhibits strong regenerative potential, positioning it as a promising bioactive agent in tissue engineering (TE). This review systematically summarizes the research progress, applications, and mechanisms of PL-loaded biomaterials in TE. PL-integrated carriers, including hydrogels, scaffolds, and nanoparticles, transform labile liquid PL into stable, tunable platforms that retain its capacities to promote cell proliferation, angiogenesis, immunomodulation, and tissue repair, while enabling spatiotemporal control of efficacy. These composites have demonstrated significant outcomes in wound healing, bone and cartilage repair, neural regeneration, and ocular disease treatment. Critical limitations are addressed, including unstandardized PL preparation, potential immune and metabolic risks, short half-life of active factors, and slow clinical translation. Proposed solutions encompass unified production guidelines, optimized carrier-based sustained-release systems, and large-scale clinical trials. Future research should prioritize interdisciplinary collaboration to enhance precision and translatability, establishing PL-based systems as core modular platforms in regenerative medicine.Keywords: platelet lysate, biomaterials, tissue engineering, tissue repair, nanoparticles
Mi Zhao,1– 3,* Peisen Liang,1– 3,* Jiayu Zhang,1– 3,* Yujiao Li,1– 3,* Wen Tian,1– 3,* Min Liu,2,3 Ya Zheng,2,3 Zhaofeng Chen2,31The First Clinical College of Medicine, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 2Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China; 3Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaofeng Chen, The First Hospital of Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, People’s Republic of China, Email czf0616@163.com Ya Zheng, The First Hospital of Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, Gansu, 730000, People’s Republic of China, Email zhengya10@126.comAbstract: Intestinal organoids can recapitulate key features of the native intestinal epithelium in vitro, including its three-dimensional architecture, cellular diversity, and certain physiological functions. As a result, they have emerged as valuable tools for investigating intestinal development, disease mechanisms, and drug discovery. Nevertheless, conventional intestinal organoids are largely generated through self-organization and often suffer from limited structural controllability, the absence of functional vascular networks, incomplete immune microenvironments, and restricted long-term culture stability. These limitations hinder their ability to faithfully reproduce the complex processes of nutrient transport, inflammatory regulation, and drug absorption observed in vivo. Recent advances in biomaterials, hydrogel systems, functional nanomaterials, three-dimensional (3D) bioprinting, and microfluidic technologies have opened new opportunities for the development of vascularized, immune-competent, and engineered intestinal organoids. By tailoring the mechanical properties, pore architecture, degradation characteristics, and bioactive modifications of hydrogels, researchers can create a more physiologically relevant three-dimensional niche for intestinal epithelial cells, endothelial cells, and immune cells. In addition, the incorporation of immune cells and microbiota-related components provides opportunities to investigate epithelial–immune interactions, inflammatory regulation, and host–microbiota crosstalk in a more physiologically relevant microenvironment. In combination with 3D bioprinting, biomimetic crypt–villus structures, vascular channels, and spatially controlled signaling gradients can be fabricated with high precision. Furthermore, the incorporation of perfusable vascular networks and microfluidic platforms improves oxygen and nutrient delivery, thereby enhancing the simulation of drug uptake, trans-epithelial transport, and immune cell trafficking. This review summarizes recent progress in the fundamental construction of intestinal organoids, vascularization strategies, immune microenvironment regulation, scaffold and hydrogel materials, the enhancement mechanisms of nanomaterials and rare-earth-based nanomaterials, 3D bioprinting approaches, and applications in drug delivery. Current challenges and future perspectives are also discussed. Vascularized intestinal organoids are expected to serve as a promising in vitro platform bridging tissue engineering, disease modeling, drug delivery research, and precision medicine.Keywords: intestinal organoids, vascularization, hydrogels, scaffold materials, 3D bioprinting, nanoparticles, drug delivery, microfluidics, immune microenvironment
Purpose:Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) checkpoint blockade has led to improvements in clinical outcomes for various advanced cancers. However, response rates remain low, and most patients present with intrinsic resistance to PD-1/PD-L1 inhibitors. Circulating soluble PD-L1 (sPD-L1) has emerged as a driver of resistance to PD-1/PD-L1 inhibitors. Elevated levels of sPD-L1 can be detected in peripheral blood in patients with cancer and are associated with poor prognosis and resistance to PD-1/PD-L1 therapy, highlighting the need to find strategies to remove sPD-L1 from circulation. Here, we evaluated the efficacy and immunological responses of using NaNots®A, a type of engineered nanoparticle that has been designed to capture sPD-L1, as a therapeutic agent to treat cancer. Methods:Different biological samples containing sPD-L1 were tested pre- and post-treatment to determine the capturing efficiency of NaNots. To evaluate the therapeutic potential of NaNots in vivo, a humanized PD-L1 mouse model was used with an sPD-L1 secreting tumor model to assess tumor growth and to immunophenotype antitumor responses. Results:NaNot treatment successfully depleted sPD-L1 from multiple sources, including patient and mouse plasma. NaNot treatment resulted in substantial tumor growth delay and increased proportions of effector CD8 T cells, concurrent with decreased immunosuppressive regulatory T cells, in tumor and spleen tissues. Conclusion:Overall, this preclinical work demonstrates that selective capture of sPD-L1 in vivo with a novel nanotherapeutic platform can reduce immune suppression concurrent with greater immune activation, thereby enabling tumor growth control.
Periodontitis is a chronic inflammatory disease associated with obesity, type 2 diabetes, and cardiovascular disease, and has become a serious public health issue. Antibacterial treatment and mechanical debridement are the main treatment strategies for periodontitis. However, side effects and bacterial resistance might lead to treatment failure. Nanotechnology systems have new opportunities for the management of periodontitis. With benefits including superior targeting and fewer side effects, drug delivery systems constructed with nanoparticles (NPs) may provide local, delayed, and regulated drug release. When combined with immunomodulatory therapy, tissue regeneration, and antibacterial therapy, a high drug loading capacity of individual medications or therapeutic combinations is made possible by the large surface area to volume ratio of nanoparticles, providing synergistic beneficial effects. This paper reviews the progress in the research and application of nanoparticle-based drug delivery systems in the treatment of periodontitis. We focused on the pathophysiology of periodontitis, introduced the rational design of nano-drug delivery systems, and concentrated on the local approaches to treatment for periodontitis. Furthermore, the future challenges and research prospects for nanoparticle-based drug delivery systems in the treatment of periodontitis are also covered in this paper.
Gene silencing by RNA interference (RNAi) has emerged as a promising strategy for cancer therapy. Small interfering RNA (siRNA), a class of small regulatory RNAs that recognize and degrade complementary target messenger RNAs (mRNAs) in a sequence-specific manner at the post-transcriptional level, plays a critical role in regulating gene expression. However, the in vivo delivery of siRNA remains a formidable challenge due to its poor physiological stability, susceptibility to enzymatic degradation, inability to efficiently cross cellular membranes, non-specific off-target effects, and immunostimulation. Overcoming these barriers and enhancing the gene silencing efficiency of siRNA in target cells is essential for the clinical translation of RNAi technology. In recent years, tumor microenvironment (TME)-responsive nanocarriers have attracted considerable attention as a strategy to improve siRNA stability, enhance its enrichment and penetration at tumor sites, facilitate cellular uptake, and promote efficient gene silencing. This review comprehensively summarized the design principles and functional characteristics of TME-responsive siRNA delivery nanocarriers, with a focus on five major stimuli: pH, hypoxia, enzymes, glutathione (GSH), and reactive oxygen species (ROS). We critically analyze the advantages and limitations of existing nanocarrier systems, provide comparative insights through summary tables, and discuss future directions including multi-stimuli-responsive systems, combination therapies, and clinical translation challenges. This review aims to provide a systematic framework for understanding and advancing TME-responsive siRNA nanocarriers for tumor therapy.
Despite maximal safe resection and chemoradiotherapy, glioblastoma almost invariably recurs near the resection margin. Incomplete tumor removal is only one contributor; infiltrative residual cells, resistant stem-like states, wound-healing responses, local immunosuppression, and limited drug access also promote regrowth. This review examines stand-alone nanocarriers and nano-enabled composites in which nanoscale components are incorporated into hydrogels, scaffolds, or implants at the postoperative cavity-margin interface. Biomaterials lacking a functional nanoscale component are included only as design or procedural comparators. Postoperative resection models are distinguished from intratumoral, unresected orthotopic, ex vivo, and in vitro studies, which provide indirect support. Most evidence of efficacy remains preclinical, whereas human studies mainly address feasibility, safety, pharmacodynamic activity, or workflow precedent. Translation depends on reproducible retention, margin coverage, biologically matched release, brain safety, scalable manufacturing, and neurosurgical compatibility. Local nanomedicine thus remains a conditional postoperative strategy whose clinical value has yet to be established.
Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) exhibit antitumor activity, favorable biocompatibility, receptor-targeting capabilities, and amphiphilicity. These properties make them promising multifunctional components for developing antitumor drug delivery systems. Unlike previous reviews that focus on individual applications, this review systematically categorizes GL/GA according to their three functional roles. First, as therapeutic agents, GL/GA can be incorporated into passively targeted, actively targeted, and stimuli-responsive nanocarriers. They can be combined with chemotherapeutic drugs, such as cisplatin and paclitaxel, to enhance therapeutic efficacy and reduce systemic toxicity. Second, as targeting ligands, GL/GA can be conjugated to the surfaces of nanocarriers to enable receptor-mediated tumor delivery. Finally, as self-assembling materials, GL/GA can co-assemble with other drugs to form carrier-free nanostructures. Alternatively, they can serve as building blocks for polymeric carriers. These strategies enable drug-carrier integration, simplify formulation processes, and enhance synergistic antitumor effects. Furthermore, this review analyzes the key challenges in the clinical translation of these formulations. These challenges include the complexity of large-scale production, insufficient in vivo stability, a lack of long-term safety data, and inconsistencies in quality evaluation systems. Future translational prospects are also outlined to guide the rational design and clinical development of natural product-based nanomedicines.
Cancer poses an escalating threat to global public health, characterized by continuous rises in both incidence and mortality. While conventional tumor interventions including surgery, chemotherapy and radiotherapy have made considerable progress, their clinical efficacy is severely constrained by systemic toxic side effects, inadequate targeting precision and frequent severe postoperative and treatment-related sequelae. Nanodrug delivery systems have evolved as a viable therapeutic alternative to optimize tumor targeting and minimize systemic toxicity. However, conventional nanocarriers suffer from rapid clearance by the mononuclear phagocyte system, and the intricate, heterogeneous tumor microenvironment (TME) further impairs effective intratumoral drug penetration and uniform distribution. As an emerging class of living delivery vectors, probiotics have recently gained extensive research attention by virtue of their intrinsic tumor tropism, unique capacity to adapt to and remodel the TME, and excellent synergistic compatibility with multiple therapeutic regimens. This review systematically elaborates the biological mechanisms governing the tumor-targeted accumulation and TME-responsive properties of probiotics, summarizes core strategies for probiotic genetic modification and hybrid system construction, and compares the strengths and applicable scenarios of diverse probiotic chassis strains. We further discuss the synergistic potential of probiotic-based platforms combined with immunotherapy, chemotherapy, radiotherapy and physical therapy. Finally, this article underscores the key bottlenecks and future research directions for the clinical translation of probiotic-based antitumor therapeutics, aiming to provide rigorous theoretical support for their broader clinical application in cancer treatment.
