Aji Najihudin,1,2 Miski Aghnia Khairinisa,3 Anis Yohana Chaerunisaa,4 Muhaimin Muhaimin,5,6 Eko Sri Wahyuningsih,7 Barmi Hartesi8 1Doctoral Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 2Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Garut, Garut, 44151, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 4Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 5Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 6Center of Herbal Study, Universitas Padjadjaran, Jatinangor, 45363, Indonesia; 7Department of Pharmaceutical Biology, Faculty of Pharmacy, Buana Perjuangan Karawang University, Karawang, 41361, Indonesia; 8Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi, 40531, IndonesiaCorrespondence: Muhaimin Muhaimin, Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, 45363, Indonesia, Tel +6281394014688, Email muhaimin@unpad.ac.idAbstract: Solid micro- and nanoparticulate delivery systems have attracted increasing interest as strategies to improve the delivery of herbal extract combinations for diabetes management. This review critically examines formulation approaches, physicochemical characteristics, encapsulation performance, antidiabetic activities, and evidence of synergistic or complementary interactions among co-delivered bioactive compounds. Relevant studies investigating solid micro- and nanoparticulate systems containing combinations of herbal extracts or herbal extracts with purified phytochemicals were evaluated, with particular attention to formulation performance, biological effects, and translational limitations. These delivery systems may improve phytochemical stability, protect bioactive constituents from degradation, and modulate release profiles. Reported antidiabetic effects include the regulation of glucose metabolism, inhibition of carbohydrate-digesting enzymes, modulation of oxidative stress and inflammatory pathways, and protection of pancreatic β-cells. However, enhanced biological activity following encapsulation does not necessarily establish pharmacological synergy, as the observed effects may also reflect additive or complementary interactions, improved compound delivery, or intrinsic carrier activity. Furthermore, the available evidence is predominantly preclinical, and human evidence specifically evaluating particulate delivery of herbal extract combinations remains limited. Important challenges include botanical and formulation standardization, carrier-related safety, long-term toxicity, biodistribution, manufacturing reproducibility, scalability, and regulatory requirements. Overall, solid micro- and nanoparticulate delivery systems offer promising formulation strategies for herbal extract combinations, but their therapeutic potential requires further validation through rigorous interaction studies, pharmacokinetic and safety assessments, and appropriately designed clinical trials.Graphical Abstract: An infographic of herbal extract combinations, micro and nanoparticle delivery, anti-diabetic mechanisms, outcomes.A) Heading: COMBINATION OF HERBAL EXTRACTS. List: Extract A; Extract B; Extract C; Extract D;. B) Heading: SOLID MICRO- AND NANOPARTICLE DELIVERY SYSTEMS. Central labeled parts: Targeting Ligand; PEG Chain; Biodegradable Polymeric Matrix; Encapsulated Phytochemicals; Lipid Anchor. Size labels: Nanoparticle (10 to 200 nm); Microparticle (1 to 100 micrometers). Text: Enhanced stability, protection from degradation & controlled release. C) Heading: SYNERGISTIC ANTI-DIABETIC MECHANISMS. Items: down arrow Blood glucose levels; down arrow Carbohydrate-digesting enzymes (a-glucosidase, a-amylase); up arrow Protection of pancreatic beta-cells; down arrow Antioxidant & anti-inflammatory effects; up arrow Improved insulin sensitivity. Text: Synergistic interaction of multiple bioactives leads to enhanced efficacy. D) Heading: IMPROVED THERAPEUTIC OUTCOMES. Items: Better glycemic control; Reduced risk of diabetic complication; Safer, natural and effective alternative; Improved quality of life. Banner text: KEY ADVANTAGES OF SOLID MICRO- AND NANOPARTICULATE SYSTEMS. Items: Enhanced stability; Targeted delivery; Improved bioavailability; Controlled release; Natural and safe. Arrow key: up arrow Increase or enhancement; down arrow Decrease or reduction. Text: Solid micro- and nanoparticulate delivery systems of extract combinations are a promising strategy for effective and safe diabetes management through synergistic natural bioactives.Keywords: microparticulate, nanoparticulate, extract combination, natural bioactives, diabetes management
Xuan Zhao,1– 4,* Yukun Liu,5,* Yesen Shou,1– 4 Zhikai Xu,1– 4 Xiangjun Bai,1– 4 Fangli Gao,6 Zhanfei Li,1– 4 Yuchang Wang1– 4 1Division of Trauma Surgery, Emergency Surgery & Surgical Critical, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Sino-German Research Institute of Disaster Medicine, Wuhan, 430030, People’s Republic of China; 5Department of Plastic and Aesthetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 6School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanfei Li; Yuchang Wang, Email lezhfei@163.com; tjwangyuchang@163.comAbstract: The host immune status frequently shifts from hyperinflammation toward immunosuppression—although the two states can overlap from onset and vary by tissue compartment and patient—while multiple organs undergo sequential injury. Sepsis progresses along a highly dynamic trajectory. This complexity demands therapeutic platforms that adapt to evolving pathological cues. Exosome-mimetic nanoplatforms combining the biointerfacial properties of exosomes respond independently to specific pathological signals—reactive oxygen species, pH, and dysregulated enzymes. By chemical orthogonality, we mean the independent activation of distinct functional modules by distinct pathological cues without cross-interference. We deconstruct properties of natural exosomes with the chemical tunability of synthetic nanomaterials; this can meet this demand if their design moves beyond structural mimicry toward programmable responsiveness. Here we argue these platforms should be engineered as spatiotemporally programmable systems, with distinct diagnostic and therapeutic functions encoded by chemically orthogonal modules, sepsis pathophysiology translated into actionable chemical design requirements, and examine how membrane engineering, compositional programming, and stimulus-responsive chemistries achieve trajectory-matched sensing, drug release, and immune reprogramming within a single nanosystem, distinguishing systems with uncoupled multi-function execution from simple co-delivery. It should be stated at the outset that no platform described to date fully achieves module independence; the framework therefore defines a design target and research agenda rather than a description of current capabilities. The analysis is based on a systematic screening of PubMed, Web of Science, Embase, and Scopus (2010– 2025), from which the included publications were re-examined against explicit criteria for classifying orthogonal multi-function execution versus co-delivery (Search Strategy and Classification Criteria). We also identify the translational barriers unique to chemically programmable nanotheranostics, including in vivo orthogonality fidelity, manufacturing complexity, and regulatory ambiguity. Applications are re-evaluated through the lens of chemical orthogonality. By connecting the dynamic biology of sepsis with orthogonal chemical design, this review offers guidance for developing exosome-mimetic nanomedicines and a transferable paradigm for other complex diseases.Keywords: sepsis, exosome-mimetic nanoplatforms, spatiotemporal programmability, chemical orthogonality, stimulus-responsive nanotheranostics
Iris Xiaoxue Yin,1 Veena Wenqing Xu,1 John Yun Niu,1 Xueqi Gan,2 Chun Hung Chu1 1Faculty of Dentistry, University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Chun Hung Chu, Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong Special Administrative Region, 000000, People’s Republic of China, Email chchu@hku.hkAim: Nanotechnology is emerging as a powerful tool in regenerative dentistry by supporting biological repair of enamel, dentin, pulp, periodontal tissues and alveolar bone. This narrative review outlines how nanotechnology provides a versatile platform for achieving regenerative dentistry by enabling targeted remineralization, controlled therapeutic delivery, and biomimetic tissue regeneration.Methods: This review synthesizes current evidence from in vitro and in vivo studies, material science research, and recent reviews. Relevant literature was identified through electronic searches in PubMed, Scopus and Web of Science up to February 2026, focusing on publications that investigate the mechanisms, efficacy, and applications of nanoparticles in regenerative dental therapies. Search terms included (nanoparticle OR nano OR nanomaterial) AND (regeneration OR regenerative OR remineralization OR mineralization) AND (enamel OR dentin OR pulp OR gingiva OR periodontal ligament OR cementum OR alveolar bone OR dental OR tooth OR oral).Results: A total of 71 representative publications were selected. These studies focused on the use of nanoparticles for hard tissue remineralization, scaffold-enhanced regeneration, targeted drug delivery, and antimicrobial action in dental contexts. The findings indicate that nanoparticles promote hard tissue remineralization through calcium phosphate and hydroxyapatite systems that diffuse into subsurface lesions and nucleate new mineral formation. For alveolar bone regeneration, hydroxyapatite and bioactive glass nanoparticles provide osteoconductive scaffolds and osteoinductive ion signaling. In periodontal and pulp regeneration, nanoparticle-enhanced scaffolds support stem cell proliferation and differentiation through controlled growth factor delivery. Antimicrobial nanoparticles, particularly silver and zinc oxide, provide multi-target biofilm disruption with reduced resistance risk. The evidence base is predominantly preclinical, and routine clinical application is not yet supported by available data.Conclusion: Nanoparticles support dental tissue regeneration through mechanisms such as controlled ion release, sustained growth factor delivery, and antimicrobial activity. Key challenges include ensuring long-term biocompatibility, controlling degradation and potential toxicity, and establishing clear regulatory pathways.Keywords: nanoparticles, nanotechnology, regenerative dentistry, remineralization, regeneration
Sarvin Tabibzadeh,1,* Fansu Meng,2,* Vahid Asghariazar,1 Elham Safarzadeh,1 Ali Esmaeili,1 Timo LM Ten Hagen,3 Leila Farhoudi,1 Yu Cai41Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528400, People’s Republic of China; 3Nanomedicine Innovation Center Erasmus (NICE), Erasmus MC Cancer Institute, Rotterdam, 3015 GD, the Netherlands; 4State Key Laboratory of Bioactive Molecules and Draggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/Guangdong Key Laboratory of Traditional Chinese Medicine Informatization/International Science and Technology Cooperation Base of Guangdong Province/School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Leila Farhoudi, Email l.farhoudi@arums.ac.ir; Farhoudil96@gmail.com Yu Cai, Email caiyu8@sohu.comAbstract: Cancer vaccines have emerged as a promising immunotherapeutic strategy for inducing durable and tumour-specific immune responses; however, their clinical efficacy remains limited by poor antigen immunogenicity, inefficient delivery, tumor heterogeneity, and the highly immunosuppressive tumor microenvironment (TME). Recent advances in nanotechnology have expanded opportunities for the rational engineering of multifunctional nanoparticle (NP) platforms that can protect therapeutic cargo, enhance antigen presentation and lymphatic transport, co-deliver immunostimulatory adjuvants, and potentially improve immune modulation while reducing systemic exposure. This narrative review provides an overview of next-generation cancer nanovaccines, including lipid-, polymer-, peptide-, inorganic-, biomimetic-, theranostic, in situ-, and stimuli-responsive platforms, with emphasis on their physicochemical design principles, mechanisms of immune activation, and interactions with the TME. Particular attention is given to strategies targeting tumor -associated macrophages, myeloid-derived suppressor cells, regulatory T cells, cancer-associated fibroblasts, and tumor cells to support dendritic-cell maturation, cytotoxic T-cell activation, and anti-tumor immunity. Emerging personalized approaches, including neoantigen- and autologous cell-based nanovaccines, mRNA vaccine platforms, and combinations with immune checkpoint inhibitors, are also discussed. In addition, we examine the growing role of artificial intelligence, machine learning, and computational immunology in neoantigen prioritization, nanoparticle formulation optimization, immunogenicity prediction, and patient-specific vaccine design. Despite encouraging preclinical findings, most cancer nanovaccine platforms remain at the preclinical or early clinical stage, and translation is limited by tumor heterogeneity, variable immune responses, long-term safety and biodistribution concerns, manufacturing reproducibility, scale-up, and regulatory requirements. Overall, the integration of nanotechnology, immunology, precision medicine, and AI offers considerable potential to advance personalized cancer vaccination, but broader clinical validation and standardized manufacturing and evaluation frameworks are required before these platforms can achieve routine clinical application.Keywords: cancer nanovaccines, tumor microenvironment, cancer immunotherapy, artificial intelligence, precision oncology
Daokui Li,1,2 Weifeng Yin,1– 3 Peng Liu,1,2 Xianfeng Liu,1,2 Baisheng Nie1,21State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing, 400044, People’s Republic of China; 2School of Resources and Safety Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China; 3Beijing Tiandi Rongchuang Technology Co., Ltd, Beijing, 100013, People’s Republic of ChinaCorrespondence: Daokui Li, Email dkli@cqu.edu.cn Weifeng Yin, Email 13901131533@139.comPurpose: Smart drug delivery systems enabling on-demand release and multimodal therapy are highly desirable for cancer treatment. Natural attapulgite (ATP) nanoclay possesses high surface area, good biocompatibility, and intrinsic near-infrared (NIR) absorption. This study aimed to develop an ATP-based nanoformulation incorporating gypenosides, inulin, folic acid, and lauric acid as a phase-change gatekeeper, and to evaluate its in vitro performance under NIR irradiation.Methods: The formulation was prepared by spray-drying ATP with gypenosides, inulin, and folic acid, followed by lauric acid encapsulation. Characterization included morphology, pore structure, thermal properties, and photothermal conversion. In vitro drug release was assessed with or without 808 nm NIR irradiation. Cytotoxicity against HeLa cells was evaluated using the CCK-8 assay, comparing material alone, NIR alone, and material combined with NIR.Results: The optimized microspheres (ATP-M) exhibited a hierarchical porous structure (surface area 27.0 m2/g, average pore diameter 22.3 nm) and high lauric acid loading (~51 wt%). Lauric acid melted at ~43 °C, enabling NIR-triggered release. ATP-M showed efficient NIR absorption and photothermal heating. The combination of drug-loaded microspheres and NIR irradiation reduced HeLa cell viability to 24.9%, which was lower than chemotherapy alone (51.6%) or photothermal therapy alone (83.3%).Conclusion: The natural ATP-based nanoformulation enables NIR-triggered drug release and enhanced in vitro antitumor efficacy. These findings support further investigation of this system for potential cancer therapy, including in vivo validation of targeting and synergy.Keywords: nanoclay, targeted drug delivery, phase change material, NIR-triggered drug release, chemo-photothermal synergistic therapy
