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Abstract The native extracellular matrix is continuously remodeled to form complex interconnected network structures that reversibly regulate stem cell behaviors. Both regulation and understanding of its intricate dynamicity can help to modulate numerous cell behaviors. However, neither of these has yet been achieved due to the lack of designing and modeling such complex structures with dynamic controllability. Here we report modularity-based mathematical modeling of extracellular matrix-emulating ligand inter-cluster connectivity using the graph theory. Increasing anisotropy of magnetic nano-blockers proportionately disconnects arginine-glycine-aspartic acid ligand-to-ligand interconnections and decreases the number of ligand inter-cluster edges. This phenomenon deactivates stem cells, which can be partly activated by linearizing the nano-blockers. Remote cyclic elevation of high-anisotropy nano-blockers flexibly generates nano-gaps under the nano-blockers and augments the number of ligand inter-cluster edges. Subsequently, integrin-presenting stem cell infiltration is stimulated, which reversibly intensifies focal adhesion and mechanotransduction-driven differentiation both in vitro and in vivo. Designing and systemically modeling extracellular matrix-mimetic geometries opens avenues for unraveling dynamic cell-material interactions for tissue regeneration.

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol–gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

Abstract Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.

Abstract Wireless energy transfer (WET) based on ultrasound‐driven generators with enormous beneficial functions, is technologically in progress by the valuation of ultrasonic metamaterials (UMMs) in science and engineering domains. Indeed, novel metamaterial structures can develop the efficiency of mechanical and physical features of ultrasound energy receivers (US‐ETs), including ultrasound‐driven piezoelectric and triboelectric nanogenerators (US‐PENGs and US‐TENGs) for advantageous applications. This review article first summarizes the fundamentals, classification, and design engineering of UMMs after introducing ultrasound energy for WET technology. In addition to addressing using UMMs, the topical progress of innovative UMMs in US‐ETs is conceptually presented. Moreover, the advanced approaches of metamaterials are reported in the categorized applications of US‐PENGs and US‐TENGs. Finally, some current perspectives and encounters of UMMs in US‐ETs are offered. With this objective in mind, this review explores the potential revolution of reliable integrated energy transfer systems through the transformation of metamaterials into ultrasound‐driven active mediums for generators.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens. Its effective use as a cancer therapy requires a precisely targeted approach, which can be facilitated by using nanoparticles and nanomedicine, and their use to enhance ferroptosis is indeed a growing area of research. While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles, there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine. Furthermore, magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging (MRI). The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine. Here, recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized. This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine. Finally, image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations.

Abstract Osteoarthritis (OA) is a chronic and degenerative disease with limited clinical options for effective suppression. Recently, significant endeavors have been explored to reveal its pathogenesis and develop treatments against OA. Hydrogels, designed with a striking resemblance to the extracellular matrix, offer a biomimetic interaction with biological tissues, presenting a promising avenue for OA amelioration. As a result, biocompatible hydrogels have been erected incorporating on‐demand bioactivities to optimize the intra‐articular microenvironment, thereby alleviating OA symptoms and fostering the eventual regeneration of articular joints. This review highlights the collaborative objectives underlying the establishment of this tissue microenvironment, encompassing mechanical modulation, anti‐inflammation, and tissue regeneration. Specifically, we consolidate recent advances in hydrogel‐based biomaterials, serving as the tissue engineering scaffolds to replicate the lubrication properties of natural joints or the bioactive agent‐loaded vehicles to combat localized inflammation. Additionally, hydrogels function as cell scaffolds to facilitate the maintenance of cellular homeostasis and contribute to the advancement of cartilage regeneration. Finally, this review outlines the prospective directions for hydrogel‐mediated OA therapies.

The trade-off relationship between cost and performance is a major challenge in the development of surface-enhanced Raman spectroscopy (SERS) sensors for practical applications. We propose a roll-to-roll system with incorporated vacuum sputtering to manufacture Ag-coated nanodimples (Ag/NDs) on A4-scale films in a single step. The Ag/ND SERS platforms were prepared via O2 ion beam sputtering and Ag sputtering deposition. The concave three-dimensional spaces in the Ag/NDs functioned as hotspots, and their optimal fabrication conditions were investigated with two variables: moving speed and Ag thickness. The entire process was automated, which resulted in highly consistent optical responses (i.e., relative standard deviation of ∼10%). The activation of plasmonic hotspots was demonstrated by electric-field profiles calculated via the finite-difference time-domain method. The wavelength dependency of the Ag/ND platforms was also examined by dark-field microscopy. The results indicate that the developed engineering technique for the large-scale production of Ag/ND plasmonic chips would likely be competitive in the commercial market.

Diverse connective tissues exhibit hierarchical anisotropic structures that intricately regulate homeostasis and tissue functions for dynamic immune response modulation. In this study, remotely manipulable hierarchical nanostructures are tailored to exhibit multi-scale ligand anisotropy. Hierarchical nanostructure construction involves coupling liganded nanoscale isotropic/anisotropic Au (comparable to few integrin molecules-scale) to the surface of microscale isotropic/anisotropic magnetic Fe3O4 (comparable to integrin cluster-scale) and then elastically tethering them to a substrate. Systematic independent tailoring of nanoscale or microscale ligand isotropy versus anisotropy in four different hierarchical nanostructures with constant liganded surface area demonstrates similar levels of integrin molecule bridging and macrophage adhesion on the nanoscale ligand isotropy versus anisotropy. Conversely, the levels of integrin cluster bridging across hierarchical nanostructures and macrophage adhesion are significantly promoted by microscale ligand anisotropy compared with microscale ligand isotropy. Furthermore, microscale ligand anisotropy dominantly activates the host macrophage adhesion and pro-regenerative M2 polarization in vivo over the nanoscale ligand anisotropy, which can be cyclically reversed by substrate-proximate versus substrate-distant magnetic manipulation. This unprecedented scale-specific regulation of cells can be diversified by unlimited tuning of the scale, anisotropy, dimension, shape, and magnetism of hierarchical structures to decipher scale-specific dynamic cell-material interactions to advance immunoengineering strategies.

The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1 (TGF-β1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-β1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.

Intracranial dural arteriovenous fistula (DAVF) is an abnormal arteriovenous shunt accounting for approximately 10%–15% of all intracranial vascular malformations. Most intracranial DAVFs are solitary, but multiple lesions at different sites can rarely occur. Most intracranial multiple DAVFs are synchronous types, whereas metachronous lesions are relatively uncommon. Herein, we report a rare case of metachronous DAVF occurring after the embolization of a preceding lesion in a 75-year-old female.

Abstract Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.

Abstract The extracellular matrix (ECM) is a highly dynamic system that constantly offers physical, biological, and chemical signals to embraced cells. Increasing evidence suggests that mechanical signals derived from the dynamic cellular microenvironment are essential controllers of cell behaviors. Conventional cell culture biomaterials, with static mechanical properties such as chemistry, topography, and stiffness, have offered a fundamental understanding of various vital biochemical and biophysical processes, such as cell adhesion, spreading, migration, growth, and differentiation. At present, novel biomaterials that can spatiotemporally impart biophysical cues to manipulate cell fate are emerging. The dynamic properties and adaptive traits of new materials endow them with the ability to adapt to cell requirements and enhance cell functions. In this review, an introductory overview of the key players essential to mechanobiology is provided. A biophysical perspective on the state‐of‐the‐art manipulation techniques and novel materials in designing static and dynamic ECM‐mimicking biomaterials is taken. In particular, different static and dynamic mechanical cues in regulating cellular mechanosensing and functions are compared. This review to benefit the development of engineering biomechanical systems regulating cell functions is expected.

Stenosis of the central veins is a common complication in hemodialysis patients. However, cerebral venous hypertension and neurological symptoms caused by central vein stenosis are relatively rare. We present a rare case of cerebral venous hypertension in a 63-year-old male who showed venous reflux into the dural sinuses due to central venous stenosis on time-of-flight MR angiography. After management for central venous stenosis, the venous reflux disappeared.

Abstract Two-dimensional (2D) MXenes are promising as electrode materials for energy storage, owing to their high electronic conductivity and low diffusion barrier. Unfortunately, similar to most 2D materials, MXene nanosheets easily restack during the electrode preparation, which degrades the electrochemical performance of MXene-based materials. A novel synthetic strategy is proposed for converting MXene into restacking-inhibited three-dimensional (3D) balls coated with iron selenides and carbon. This strategy involves the preparation of Fe2O3@carbon/MXene microspheres via a facile ultrasonic spray pyrolysis and subsequent selenization process. Such 3D structuring effectively prevents interlayer restacking, increases the surface area, and accelerates ion transport, while maintaining the attractive properties of MXene. Furthermore, combining iron selenides and carbon with 3D MXene balls offers many more sites for ion storage and enhances the structural robustness of the composite balls. The resultant 3D structured microspheres exhibit a high reversible capacity of 410 mAh g−1 after 200 cycles at 0.1 A g−1 in potassium-ion batteries, corresponding to the capacity retention of 97% as calculated based on 100 cycles. Even at a high current density of 5.0 A g−1, the composite exhibits a discharge capacity of 169 mAh g−1.

Abstract An innovative autonomous resonance‐tuning (ART) energy harvester is reported that utilizes adaptive clamping systems driven by intrinsic mechanical mechanisms without outsourcing additional energy. The adaptive clamping system modulates the natural frequency of the harvester's main beam (MB) by adjusting the clamping position of the MB. The pulling force induced by the resonance vibration of the tuning beam (TB) provides the driving force for operating the adaptive clamp. The ART mechanism is possible by matching the natural frequencies of the TB and clamped MB. Detailed evaluations are conducted on the optimization of the adaptive clamp tolerance and TB design to increase the pulling force. The energy harvester exhibits an ultrawide resonance bandwidth of over 30 Hz in the commonly accessible low vibration frequency range (

Multifunctional magnetic nanoparticles (MNPs) exhibit unique properties, such as remote motion controllability, degradability, and diagnostic imaging, which are typically not shown in nonmagnetic nanomaterials. MNPs remotely controllable via magnetic fields offer advantages of high tissue penetrability and biocompatibility. In this review, recent advances of multifunctional MNPs exhibiting unique characteristic for therapeutic applications are summarized, which utilize the “dynamic” motion, iron ion degradation, or imaging‐guided targeting of the MNPs under diverse magnetic field modes. The magnetic field‐controlled MNP motion enables spatiotemporal and reversible in situ cell regulation and mechanosensitive molecule modulation or thermal energy generation. Furthermore, the iron‐based MNPs can produce degraded ions and reactive oxygen species to enable targeted ferroptosis therapy with medical imaging‐guided approaches. The state‐of‐the‐art imaging‐guided “dynamic” therapy using the MNPs that can provide in situ feedback at each therapeutic stage is highlighted. Potential hurdles in translating the magnetic dynamic imaging and therapy toward clinical practices are also discussed. The imaging capability of the MNPs during “dynamic” magneto‐cell regulation enables noninvasive, safe, localized, and on‐demand regulation for the state‐of‐the‐art regenerative therapy, immunotherapy, and cancer treatment.

Abstract Optical diffraction tomography (ODT) enables imaging of unlabeled intracellular components by measuring the three-dimensional (3D) refractive index (RI). We aimed to detect intracellular monosodium urate (MSU) crystals in synovial leukocytes derived from gout patients using ODT. The 3D RI values of the synthetic MSU crystals, measured by ODT, ranged between 1.383 and 1.440. After adding synthetic MSU crystals to a macrophage, RI tomograms were reconstructed using ODT, and the reconstructed RI tomograms discerned intracellular and extracellular MSU crystals. We observed unlabeled synthetic MSU crystal entry into the cytoplasm of a macrophage through time-lapse imaging. Furthermore, using gout patient-derived synovial leukocytes, we successfully obtained RI tomogram images of intracellular MSU crystals. The 3D RI identification of MSU crystals was verified with birefringence through polarization-sensitive ODT measurements. Together, our results provide evidence that this novel ODT can identify birefringent MSU crystals in synovial leukocytes of patients with gout.

Integrins are heterodimeric cell surface glycoproteins used by cells to bind to the extracellular matrix (ECM) and regulate tumor cell proliferation, migration and survival. A causative relationship between integrin expression and resistance to anticancer drugs has been demonstrated in different tumors, including head and neck squamous cell carcinoma. Using a Cal27 tongue squamous cell carcinoma model, we have previously demonstrated that de novo expression of integrin αVβ3 confers resistance to several anticancer drugs (cisplatin, mitomycin C and doxorubicin) through a mechanism involving downregulation of active Src, increased cell migration and invasion. In the integrin αVβ3 expressing Cal27-derived cell clone 2B1, αVβ5 expression was also increased, but unrelated to drug resistance. To identify the integrin adhesion complex (IAC) components that contribute to the changes in Cal27 and 2B1 cell adhesion and anticancer drug resistance, we isolated IACs from both cell lines. Mass spectrometry (MS)-based proteomics analysis indicated that both cell lines preferentially, but not exclusively, use integrin α6β4, which is classically found in hemidesmosomes. The anticancer drug resistant cell clone 2B1 demonstrated an increased level of α6β4 accompanied with increased deposition of a laminin-332-containing ECM. Immunofluorescence and electron microscopy demonstrated the formation of type II hemidesmosomes by both cell types. Furthermore, suppression of α6β4 expression in both lines conferred resistance to anticancer drugs through a mechanism independent of αVβ3, which implies that the cell clone 2B1 would have been even more resistant had the upregulation of α6β4 not occurred. Taken together, our results identify a key role for α6β4-containing type II hemidesmosomes in regulating anticancer drug sensitivity.

Control of macrophage adhesion and phenotype is important to biomaterial applications. Here, the authors report on the use of bisphosphonate coated gold nanoparticles by magnesium coordination for the controlled adhesion and polarisation of macrophages in vitro and in vivo and controlled cell release.

In the biological microenvironment, cells are surrounded by an extracellular matrix (ECM), with which they dynamically interact during various biological processes. Specifically, the physical and chemical properties of the ECM work cooperatively to influence the behavior and fate of cells directly and indirectly, which invokes various physiological responses in the body. Hence, efficient strategies to modulate cellular responses for a specific purpose have become important for various scientific fields such as biology, pharmacy, and medicine. Among many approaches, the utilization of biomaterials has been studied the most because they can be meticulously engineered to mimic cellular modulatory behavior. For such careful engineering, studies on physical modulation (e.g., ECM topography, stiffness, and wettability) and chemical manipulation (e.g., composition and soluble and surface biosignals) have been actively conducted. At present, the scope of research is being shifted from static (considering only the initial environment and the effects of each element) to biomimetic dynamic (including the concepts of time and gradient) modulation in both physical and chemical manipulations. This review provides an overall perspective on how the static and dynamic biomaterials are actively engineered to modulate targeted cellular responses while highlighting the importance and advance from static modulation to biomimetic dynamic modulation for biomedical applications.

Functionalized nanomaterials of various categories are essential for developing cancer nano-theranostics for brain diseases; however, some limitations exist in their effectiveness and clinical translation, such as toxicity, limited tumor penetration, and inability to cross blood–brain and blood-tumor barriers. Metal nanomaterials with functional fluorescent tags possess unique properties in improving their functional properties, including surface plasmon resonance (SPR), superparamagnetism, and photo/bioluminescence, which facilitates imaging applications in addition to their deliveries. Moreover, these multifunctional nanomaterials could be synthesized through various chemical modifications on their physical surfaces via attaching targeting peptides, fluorophores, and quantum dots (QD), which could improve the application of these nanomaterials by facilitating theranostic modalities. In addition to their inherent CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PAI (Photo-acoustic imaging), and X-ray contrast imaging, various multifunctional nanoparticles with imaging probes serve as brain-targeted imaging candidates in several imaging modalities. The primary criteria of these functional nanomaterials for translational application to the brain must be zero toxicity. Moreover, the beneficial aspects of nano-theranostics of nanoparticles are their multifunctional systems proportioned towards personalized disease management via comprising diagnostic and therapeutic abilities in a single biodegradable nanomaterial. This review highlights the emerging aspects of engineered nanomaterials to reach and deliver therapeutics to the brain and how to improve this by adopting the imaging modalities for theranostic applications.

Engineering polymeric nanoparticles for their shape, size, surface chemistry, and functionalization using various targeting molecules has shown improved biomedical applications for nanoparticles. Polymeric nanoparticles have created tremendous therapeutic platforms, particularly applications related to chemo- and immunotherapies in cancer. Recently advancements in immunotherapies have broadened this field in immunology and biomedical engineering, where “immunoengineering” creates solutions to target translational science. In this regard, the nanoengineering field has offered the various techniques necessary to manufacture and assemble multifunctional polymeric nanomaterial systems. These include nanoparticles functionalized using antibodies, small molecule ligands, targeted peptides, proteins, and other novel agents that trigger and encourage biological systems to accept the engineered materials as immune enhancers or as vaccines to elevate therapeutic functions. Strategies to engineer polymeric nanoparticles with therapeutic and targeting molecules can provide solutions for developing immune vaccines via maintaining the receptor storage in T- and B cells. Furthermore, cancer immunotherapy using polymeric nanomaterials can serve as a gold standard approach for treating primary and metastasized tumors. The current status of the limited availability of immuno-therapeutic drugs highlights the importance of polymeric nanomaterial platforms to improve the outcomes via delivering anticancer agents at localized sites, thereby enhancing the host immune response in cancer therapy. This review mainly focuses on the potential scientific enhancements and recent developments in cancer immunotherapies by explicitly discussing the role of polymeric nanocarriers as nano-vaccines. We also briefly discuss the role of multifunctional nanomaterials for their therapeutic impacts on translational clinical applications.