Mesenchymal stromal cell-derived artificial microvesicles (MSC-MVs) hold significant promise as a cell-free alternative to traditional stem cell therapy for the treatment of lower limb ischemia. However, their fragile plasma membrane is highly susceptible to oxidative damage, environmental fluctuations, and long-term storage, often leading to membrane rupture, vesicle disintegration, and leakage of bioactive cargoes. Additionally, MSC-MVs can be contaminated by nuclear genes, limiting their safety and therapeutic applicability. In this study, we developed gelated microvesicles (gel-MVs) derived from enucleated MSCs by incorporating a polyethylene glycol diacrylate (PEGDA) polymer network within the vesicular lumen. This intravesicular gelation process stabilized the structure of MSC-MVs, effectively preventing vesicle degradation and content leakage. experiments demonstrated that gelation preserved the integrity of bioactive components and maintained their functional activity. In a murine lower limb ischemia model, gel-MVs significantly enhanced angiogenesis, restored blood perfusion, reduced apoptosis, and promoted tissue regeneration in ischemic limbs. This study introduces a novel strategy that integrates artificial polymer networks with natural microvesicles, providing a promising platform for engineering robust and functional MSC-MVs with enhanced therapeutic potential for clinical translation.

Myocardial infarction (MI), a leading cause of global cardiovascular mortality, is characterized by a vicious cycle of oxidative stress and inflammatory responses, resulting in irreversible myocardial damage and ventricular remodeling. To address the limitations of current therapies in comprehensively targeting the post-MI pathological microenvironment, this study developed an injectable hydrogel system, termed CPH (DS/CMCS), through the rational integration of carboxymethyl chitosan (CMCS), dextran sulfate (DS), and oxidized dextran (ODex) as a dynamic crosslinker. The CPH hydrogel not only mimicked the mechanical properties of the native myocardial extracellular matrix but also integrated multifunctional capabilities, including antioxidant activity, anti-inflammatory effects, pro-angiogenic potential, and enhanced electrical signal conduction. Through both cellular and animal studies, it was conclusively shown that the CPH hydrogel effectively scavenged reactive oxygen species (ROS), protected cardiomyocytes from oxidative damage, modulated macrophage polarization to mitigate inflammatory cascades, and promoted vascular regeneration and myocardial remodeling. In the rat MI model, the CPH hydrogel significantly improved cardiac function and achieved comprehensive structural restoration of infarcted myocardium. This study introduces an innovative acellular spatiotemporal approach for the treatment of MI and advances the rational design of cardiac tissue-engineered biomaterials, highlighting its substantial clinical translation potential for regenerative medicine.

The accumulation of Tau aggregates is commonly linked with various neurodegenerative diseases, such as Alzheimer's disease, Pick's disease, and corticobasal degeneration. Notwithstanding substantial investments in the development of clinical strategies for effective intervention, traditional design paradigms are predominantly confined to molecules featuring either a solitary function or single-dimensional mode of intervention, ignoring the necessity of personalized and precise medicine. Herein, we design and synthesize a dual-functional aggregation-induced emission-active agent to serve as both a fluorescent probe for the imaging of pathological Tau and a modulator for intervention. This amphiphilic theranostic agent, named TPE-P9, is prepared a one-pot Michael reaction between hydrophobic maleimide-modified tetraphenylethylene (TPE-Mal) and a hydrophilic cysteine-modified Tau-targeting peptide (CKVQIINKK). Microscale thermophoresis measurement and fluorescence analysis demonstrate that TPE-P9 exhibits specific binding affinity ( = 4.46 µM) and high selectivity towards Tau fibrils, featuring a pronounced low background interference, which is superior to the classical amyloid protein probe thioflavin T (ThT). At the living cellular level, TPE-P9 is capable of readily imaging endogenic pathological Tau to distinguish normal neurons from the lesional neurons , and the staining consequence is almost consistent with that of ThT. On the other hand, as a modulator, TPE-P9 can potently protect neurons from cytotoxic Tau-induced apoptosis both by inhibiting aberrant post-translational modification-induced Tau self-assembly and by blocking the produced pathological Tau propagation, enhancing cell viability by 35.4%. These findings offer valuable insights for the development of innovative image-guided therapeutic strategies for targeted tauopathies treatment.

Inhibiting and reducing bacterial infections associated with biomedical implants and devices remains a significant challenge. In this study, we successfully grafted crosslinked antifouling and bactericidal coatings onto a polyurethane (PU) surface using sulfobetaine (SB) zwitterionic and quaternary ammonium cationic (QAC) copolymers through a combination of PDA-assisted co-deposition and amidation reactions. The successful formation and surface properties of the crosslinked coatings were characterized using Fourier transform infrared spectroscopy (FT-IR), water contact angle (WCA) measurements, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), electrochemical corrosion tribometry (MFT-EC), and atomic force microscopy (AFM). The antifouling performance was evaluated protein adsorption, platelet adhesion, whole blood adhesion, and cytotoxicity assays. Additionally, the antibacterial and bactericidal efficacy was evaluated using , and as models. Our results indicate that the molar ratio of SB and QAC critically influences the antifouling and bactericidal properties, and a relatively high SB content (60 mol%) combined with a low QAC content (20 mol%) achieves an optimal balance between antifouling and bactericidal properties. This combination of zwitterionic and quaternary ammonium cationic copolymer modifications not only effectively kills bacteria upon contact but also prevents the adhesion of dead bacteria, demonstrating promising potential for applications in biomedical implants and devices.

The integration of discrete nanomaterials into a single platform enables the synergistic combination of their exceptional physicochemical properties, which is particularly advantageous for biomedical imaging and therapy. However, retaining the intrinsic optical features of individual components during such integration remains a major challenge. In particular, understanding the interactions between metallic nanostructures with distinct functionalities continues to be of significant scientific interest. In this study, we report the design of a novel hybrid gold nanoplatform, PEG-PGNC@HA-GNR, comprising DSPE-PEG coated protein gold nanoclusters (PGNCs) and hyaluronic acid (HA) wrapped anisotropic gold nanorods (GNRs). The PGNCs exhibit tunable near-infrared (NIR) photoluminescence, while GNRs provide efficient photothermal property. The hybrid nanoarchitecture was meticulously engineered to preserve these complementary optical features, enabling dual functionality for imaging and photothermal therapy. HA, a chiral anionic polysaccharide with high affinity for CD44 receptors, simultaneously enhanced GNR biocompatibility and induced plasmon driven chiroptical activity helical wrapping. DSPE-PEG coating on PGNCs improved stability and facilitated their conjugation with HA-GNRs, yielding a hybrid nanostructure validated by UV-Vis and fluorescence spectroscopy, zeta potential analysis and TEM. The hybrid retained significant PGNC fluorescence despite conjugation with GNRs, largely due to deliberate spatial separation minimizing energy transfer. The resulting construct displayed distinct circular dichroism (CD) signals and enhanced photothermal performance, offering a multifunctional platform for targeted cancer recognition and light-triggered therapy. Preliminary studies further demonstrated its imaging potential in mice. This work underscores the utility of naturally derived chiral ligands in engineering multifunctional plasmonic nanomaterials for precision oncology.

There is still a huge challenge in achieving efficient osseointegration between the implant and local bone tissue at the initial stage of implantation, because the bone-implant interface is usually exposed to abnormal microenvironments such as oxidative stress, infection, and bone homeostasis imbalance. Recently, polyphenol-inspired biointerfacial materials have received much attention for enhancing osseointegration due to their unique structural characteristics and biological functions. Polyphenolic biological coatings have shown great potential in providing adjustable physicochemical cues that improve biointerface interactions, thereby promoting bone integration and bone repair by regulating the tissue microenvironment and participating in cellular events. This review briefly outlines the regulatory effects of polyphenols on osteogenesis, introduces the interfacial adhesion mechanisms and construction strategies of polyphenolic coatings, and focuses on the biochemical and biophysical interactions occurring at the cell-polyphenol interface. Our aim is to offer guidance for the rational design of polyphenol related functional coatings and to accelerate the translation of polyphenol platforms from laboratory research into orthopedic clinical applications.

Manganese dioxide (MnO) nanoparticles have been reported to deliver drugs, supply oxygen and consume glutathione (GSH) to promote cancer photodynamic therapy (PDT). However, most of them suffer from low drug loading capacity and conflicting oxygen/GSH tuning, which restricts their therapeutic potential. In this study, a high capacity MnO-derived multifunctional nanocarrier was designed to alleviate tumor hypoxia, one of the most critical conditions for effective PDT, by systematically modulating local oxygen supply and GSH depletion. The prepared MnO (MH) nanoaggregates were coated with catalase (CAT) through molecular assembly and chemical crosslinking, yielding the MH@CAT nanocomposite. In the presence of hydrogen peroxide (HO), the CAT coating facilitates oxygen generation, while the MnO core remains intact until encountering intracellular GSH, resulting in MnO decomposition and GSH draining. This programmed regulation of oxygen supply and GSH consumption is a key design to optimize the tumor microenvironment for enhanced PDT. After loading chlorin e6 (Ce6), the as-prepared MH@CAT-Ce6 demonstrates improved cellular uptake, oxygen self-supply, and GSH depletion - all of which contribute to the superior PDT effects observed against breast cancer cells both and . Notably, the MH@CAT-Ce6 nanoparticles exhibit excellent tumor accumulation and retention, leading to potent anti-tumor efficacy with minimal systemic toxicity.

This study reports an approach of using a molecularly imprinted polymer (MIP) combined with Bi-doped cobalt ferrite (BiCoFeO) nanoparticles (NPs) for detecting C-reactive protein (CRP), a marker associated with cardiovascular diseases (CVDs). Sudden cardiac arrest is a growing concern in India, where CVDs have become the leading cause of mortality. MIPs have recently drawn increasing interest over time; consequently, the objective of this study is to engineer an MIP-based electrochemical sensor due to their reliability, ease of electrochemical control for template removal, and cavity renewal. MIPs are selective polymers that can bind target molecules and are synthesised using a ratio of 1 : 4 : 20 of a novel functional monomer (4-nitrophenyl methacrylate), a template (CRP), and a crosslinker (EGDMA) the bulk polymerisation method, along with BiCoFeO NPs (Bi = 0.05, 0.10, 0.15, and 0.20 M). These NPs and MIPs were characterised using powder X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) analysis, dynamic light scattering (DLS), ultraviolet-visible (UV) spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and the Brunauer-Emmett-Teller (BET) method. The synthesised NPs and MIP were fabricated onto an indium tin oxide (ITO) electrode using the electrophoretic deposition (EPD) process. Moreover, an electrochemical analysis was conducted using voltammetry and electrochemical impedance sensing (EIS) techniques for CRP detection across two linear ranges: a lower range of 0.5-80 ng mL with a limit of detection (LOD) of 0.1609 ng mL and a sensitivity of 0.740 Ω ng cm, and a higher range of 90-400 ng mL, in which the LOD was 0.3262 ng mL, sensitivity was 0.0631 Ω ng cm and the response time of the fabricated sensor was observed to be 10 seconds.

Pharmaceutical research emphasizes stereochemistry and the enantioseparation of racemic drugs because different enantiomers can exhibit varying pharmacological and toxicological properties when interacting with the body's metabolic pathways. Metal-organic frameworks (MOFs) are porous adsorbents that can be designed to possess homochirality within their structures, enabling tunable porosity and enantioselective adsorption of racemic drugs. In our study, we present the synthesis of five novel and homochiral Co-L-GG(R) MOFs (where L-GG = glycyl-L()-glutamic acid and R = bipyridyl (bipy) pillar ligands). These isoreticular MOFs were synthesized using the ligand extension strategy. This approach allowed us to systematically control the pore sizes of the MOFs, enabling fine-tuning of the enantioselective adsorption of racemic drugs, primarily DL-penicillamine (Pen). Our findings reveal that the pore size greatly influences enantioselective adsorption, where too large or too small pores hinder the proximity-driven dispersive interactions between the drug and the pore surface, resulting in poor enantioselective adsorption of Pen. We achieved an enantiomeric excess (ee) of 60.1% (L over D), increasing to a maximum 76.1% ee using Co-L-GGvinylbipy by tuning proximity interactions in saturated pores. These results were accomplished by controlling the drug saturation within the MOF pores, promoting favorable interactions.

Fluorescence imaging has become a powerful tool for visualizing nanoparticles in drug delivery systems, and multicolor fluorescence imaging offers an intuitive approach to exploring complex biological systems. Here, we present multicolor cyanine-based polylysine (PLL) dendritic dots (Cy3/Cy5/Cy7-PLL; up to eight generations) with a well-defined single-molecule structure and bright, photostable fluorescence. Using these probes, we achieved low-crosstalk three-channel tracking in live mice, enabling high-resolution, real-time visualization of nanoparticle biodistribution and within-subject comparisons that reduce inter-animal variability. By systematically modulating size and surface chemistry, we investigated how these parameters govern biodistribution, encompassing their efficacy in and tumor imaging, as well as nanoparticle tracking at both cellular and organ levels. We demonstrate that these multicolor dendritic dots serve as an advanced method for simultaneous, real-time tracking of nanoparticles with different traits, offering significant potential for future applications in various biomedical fields.

Due to its high energy and deep tissue penetration, X-ray is an ideal stimulus source for diagnosis and therapy. In the field of cancer treatment, by reasonably designing and using systems with X-ray responsiveness, it is possible to improve treatment methods or combine multiple treatment modalities, thereby improving treatment effectiveness and reducing side effects. This review aims to summarize the research progress of X-ray responsiveness in the field of cancer treatment in recent years. Specifically, it introduces the promotion of X-ray responsive radiosensitizers on X-ray radiation therapy itself, as well as the combination of radiotherapy and other cancer therapies mediated by X-ray responsive therapeutic systems, which mainly includes the combination of radiotherapy and photodynamic therapy through X-ray responsive scintillators and the combination of radiotherapy and chemotherapy through X-ray responsive drug delivery systems.

Radiotherapy is one of the most common and effective clinical treatments for tumors, but how to reduce its side effects to achieve better therapeutic outcomes remains a significant challenge. As a heavy metal, bismuth (Bi) is low-cost, safe, and possesses a high X-ray attenuation coefficient, offering new opportunities to overcome these limitations. With recent advances in nanotechnology and nanomedicine, Bi-based nanoradiosensitizers have been extensively explored for enhancing tumor radiosensitization to achieve advanced diagnosis and treatment by taking advantage of their ease of preparation and modification, high stability, low cost, and excellent biocompatibility. However, the use of Bi-based nanoradiosensitizers remains in the early stages of clinical translation. In this review, we summarize the mechanisms of interaction between X-ray and Bi-based nanoradiosensitizers, discuss smart preparation and modification strategies for achieving enhanced radiotherapy sensitization effects, address material safety and biodistribution, and outline recent research advances in radiotherapy-based synergistic diagnosis and treatment. Finally, we will discuss the challenges and research priorities facing Bi-based nanoradiosensitizers to advance their clinical application development.

Poly(-isopropylacrylamide) (pNIPAm) microgel-based etalons exhibit visual color, and can be fabricated by sandwiching a monolithic microgel layer between two thin metal layers (typically Au). The color of the devices is a direct result of the device structure, and can be dynamically tuned by varying the thickness of the microgel layer in response to external stimuli. For many applications, the robustness of the etalon's structure, the spatial uniformity of the color, and the color change kinetics are of utmost importance. In this investigation, we determined how the composition of the layers that make up the etalon impacts their performance. Specifically, the results indicated that stable etalons can be constructed by simply depositing a layer of Au on top of the microgel layer, as opposed to using a Cr adhesion layer on top of the microgels prior to Au overlayer deposition. We show that thin Au overlayers without a Cr adhesion layer produces Au films that are discontinuous in nature, which in turn directly influences the kinetics of the etalon response. We also confirm that this response pattern holds true for etalon responses to various salt solutions, presenting potential for the future application to alternative analytes of interest.

The concept of non-covalent migratory fluorescence labelling is introduced to spatially and temporally map intracellular lipids throughout a cell division cycle. This hands-off approach utilizes a small molecule BF-azadipyrromethene fluorophore, NM-ER, to first label the nuclear membrane and endoplasmic reticulum of cells at the interphase, which can migrate with the lipid components of these structures throughout mitosis as they disassemble, redistribute and reassemble prior to daughter cell separation. Through this unique approach to image capture, key prometaphase events such as lipid intrusion into the nucleus and nuclear membrane disassembly are observable, as are the stages of nuclear membrane reassembly in the telophase and lipid distribution during cytokinesis. When used alone, NM-ER can distinguish each phase of cell mitosis from lipid staining patterns, it is compatible with STED super resolution imaging, and, with an emission maximum of 648 nm, it is usable with other common GFP and nuclear DNA stains. The non-covalent NM-ER label remains associated with the originating lipid components as they undergo architectural reorganizations and changes in subcellular localization associated with mitosis. As lipid-based cell structures are influenced by numerous biological processes and mechanical forces, our approach to fluorescence imaging could offer novel perspectives into their different roles.

Mitoxantrone (MTO)-based nanoplatforms represent a significant advancement in oncological therapeutics by synergistically combining precision drug delivery with multimodal treatment strategies. Recent progress in precision pharmacokinetics, modular multifunctionality, and intelligent stimuli-responsive systems has established MTO as a cornerstone of next-generation combinatorial cancer therapy. The implementation of sophisticated nanocarrier designs has enabled high-efficiency drug encapsulation, spatiotemporally controlled release, and integration with complementary treatment modalities. These developments collectively address three major challenges in cancer therapy, including systemic toxicity, tumor microenvironment adaptation, and multidrug resistance mechanisms. This comprehensive review systematically explores the molecular pharmacodynamics underpinning MTO's multifaceted antitumor activity, the structural classification and functional engineering of advanced nanocarriers for MTO delivery, and the emergent therapeutic synergies and translational potential of MTO within nano-enabled combination therapy frameworks. Furthermore, the current technological limitations and clinical translation barriers are critically evaluated, proposing a roadmap of innovative solutions to inform future research endeavors. By converging multivalent nanocarrier systems with precision oncology principles, this work establishes a transformative framework that transcends conventional chemotherapy modalities and catalyzes the development of patient-specific cancer theranostics.

Chronic wounds remain a major clinical burden, often complicated by infections sustained within antibiotic-resistant biofilms. Smart wound dressings that combine structural support with controlled antimicrobial release are emerging as a powerful strategy to address these challenges. Among the biomaterial platforms, gelatin offers excellent biocompatibility, biodegradability, and chemical versatility, but its poor mechanical strength limits its standalone use. In this work, we present crosslinked gelatin-PEO (GG:PEO) hybrid films, stabilized with glycidoxypropyltrimethoxysilane (GPTMS), as a versatile platform for responsive wound management. By tuning the gelatin/PEO ratio, the films achieved up to a 57% increase in flexibility compared to pristine gelatin while retaining structural integrity. Antimicrobial functionality was conferred through incorporation of a novel multifunctional metal complex (MMC) comprising EDTA-chelated silver and copper ions. Crucially, the GG:PEO composition enabled modulation of drug release kinetics, providing a means to fine-tune bacterial inhibition. Optimized films suppressed bacterial growth and metabolism, with disc diffusion assays showing up to a 68% increase in inhibition zones at higher PEO ratios. Together, these findings demonstrate a robust and adaptable biomaterial system where both mechanical and antimicrobial properties can be engineered on demand. Such tunable composite films hold promise not only for advanced wound dressings but also for wider biomedical applications, including implant coatings and infection-responsive therapeutic devices.

Quick and easy prototyping methods are beneficial for accelerated product development, allowing for concepts to be realised through quick experimentation, validating predictions based on theory and modelling. A rapid subtractive method for the fabrication of metallic antennas, using laser ablation is reported here. These antennas may be designed for a wide range of wireless power reception applications, as integral parts of a powered device. In line with typical application in sub-dermal implants, we designed the antennas in this work to operate at distances similar to that of the dermis. Inductive spiral coil designs are fabricated from gold on a biocompatible soft polymer, Polydimethylsiloxane (PDMS). PDMS has low dielectric constant of 2.32-2.40 and low loss tangent of 0.04-0.06, which is advantageous for use as antenna substrate. The fabricated inductive coils on PDMS are characterized through electrical impedance spectroscopy and tested as a wireless signal receiver, coupled with a Qi standard wireless transmitting module, at an operating frequency of 100 kHz. Importantly, the fabricated coils show resonance in the operational frequency range of the Qi standard (100 kHz to 125 kHz). This is the first instance of laser ablation defined spiral antennas on biocompatible elastomeric substrates. Although the PDMS based inductive coils have high impedance of 2800 ± 300 Ω at 100 kHz, owing to the mechanical mismatch of rigid conductor and flexible substrate, this approach shows promise. Furthermore, strategies to decrease the impedance of such PDMS-based devices are also discussed.

The field of tissue engineering has been an ever-evolving discipline with a principal direction of creating artificial constructs to improve biological tissue types. Constructs used in tissue engineering arise from natural compounds, synthetic polymers, or a combination of the two to generate a hybrid biomaterial with optimized characteristics. In recent years, researchers have turned to silk fibroin (SF) as a natural source for its attractive physical characteristics and tunability. Using this platform, researchers have attempted to chemically modify SF through methacrylation to further improve its mechanical properties, thus making it a more appealing candidate for bioengineering applications. To date, the two most common methacrylating agents for synthesizing methacrylated SF across literature have been glycidyl methacrylate (GMA) and methacrylic anhydride (MA), which produce SFGMA and SFMA, respectively. However, the side-by-side characterization of SFGMA and SFMA has not been well compared with respect to their synthesis reactions and resulting degrees of methacrylation (DoM). To address this, our study developed a standardized protocol for SFGMA and SFMA synthesis in an effort to systematically compare the two NMR spectra. From this protocol, our results demonstrate GMA to be the superior methacrylating agent for its reactional consistency and DoM validity.

The design and synthesis of integrated diagnostic and therapeutic materials are urgently needed to enhance the precise phototherapy (PTT) of tumors. However, there is still an urgent need to develop high-performance organic photothermal agents with suitable theranostic properties, especially those with near-infrared second window (NIR-II) emissive potency. In this study, a BF-bridged J-aggregates on the donor-acceptor (D-A) conjugated oligomer CH-1 was designed and synthesized. With the J-aggregate strategy, D-A-type CH-1 in nanoparticles (NPs) achieved enhanced intramolecular charge transfer and thus redshifted the absorption. Under 808 nm laser illumination, the CH-1 NPs achieved a high photothermal conversion efficiency of 66.8% for PTT, resulting in sufficient NIR-II fluorescence emission. experiments demonstrated that CH-1 NPs could produce enough local heat upon continuous laser illumination, resulting in apoptosis-mediated tumor cell death. experiments demonstrated the effectiveness of CH-1 NPs in high-resolution NIR-II imaging whole-body angiography and tumor accumulation beyond 1400 nm. Subsequently, tumor homing and the performance of CH-1 NPs in tumor elimination were further demonstrated in a tumor-bearing mouse model. This study provides a paradigm for the development of NIR J-aggregate nanomedicines, achieving high-performance tumor phototheranostics with good biosafety.

Blood-contacting devices provide dual risks of thrombosis and infection in clinical applications. Conventional anticoagulants cause adverse effects and exhibit inadequate stability in hypercoagulable states. In this study, we broke away from the traditional understanding that zwitterionic hydrophilic groups dominate anti-fouling properties. We synthesized a ternary copolymer (PMLT) from MPC, LMA, and TSMA to investigate hydrophilic group proportion effects on thrombosis resistance, especially in hypercoagulable blood. Simply increasing the density of phosphocholine (PC) groups in the coating resulted in the coating losing its anticoagulant efficacy in hypercoagulable blood. Conversely, the composition-optimized PMLT-12 coating maintained a stable biomimetic bilayer structure. It demonstrated low protein adsorption and high antibacterial activity under normal conditions. Crucially, PMLT-12 retained excellent anti-thrombotic performance in challenging environments, including blood containing elevated levels of calcium ions and lipopolysaccharides (LPS), and blood from a diabetic animal model. The covalently crosslinked network mediated by TSMA concurrently enhanced the mechanical stability of the coating. This study highlights the critical role of hydrophobic-hydrophilic balance in anticoagulant efficacy against high coagulation risk, providing a novel strategy for improving blood-contacting device surfaces.

Cutaneous squamous cell carcinoma (cSCC) remains a formidable clinical challenge, constrained by the drawbacks of current treatments such as functional loss from surgery, radioresistance, and low adherence to protracted topical regimens. To address these issues, we designed a "photo-immuno nano-bomb" composed of polydopamine nanoparticles (PDA NPs) for co-delivering the photosensitizer chlorin e6 (Ce6) and toll-like receptor 7 agonist imiquimod (R837), thereby integrating photothermal (PTT), photodynamic (PDT), and immunotherapeutic modalities. The system utilizes π-π stacking to achieve high drug loading and stability while exhibiting a dual stimuli-responsive release profile - governed by pH-dependent surface charge alteration and photothermally triggered payload liberation - enabling more precise spatiotemporal control over combination therapy. Remarkably, the nanoformulation potently suppressed tumor cell proliferation, migration, and invasion by activating apoptotic pathways. Mechanistic studies revealed that under dual-wavelength laser irradiation (660 + 808 nm), PDA-mediated PTT enhanced cellular internalization of the nanoplatform and further augmented singlet oxygen generation, ultimately inducing mitochondrial dysfunction and cytoskeletal disintegration. This synergistic action provoked severe cellular oxidative stress and organelle damage, culminating in robust immunogenic cell death (ICD). Additionally, the platform demonstrated excellent biocompatibility, achieving complete tumor regression , outperforming all mono- and combination therapy controls. Thus, this "photo-immuno nano-bomb" multimodal strategy represents a promising therapeutic alternative for advanced cSCC, delivering superior efficacy through coordinated molecular mechanisms and minimized systemic toxicity.