Nano revolution of DNA nanostructures redefining cancer therapeutics-A comprehensive review.

DNA nanostructures are a promising tool in cancer treatment, offering an innovative way to improve the effectiveness of therapies. These nanostructures can be made solely from DNA or combined with other materials to overcome the limitations of traditional single-drug treatments. There is growing interest in developing nanosystems capable of delivering multiple drugs simultaneously, addressing challenges such as drug resistance. Engineered DNA nanostructures are designed to precisely deliver different drugs to specific locations, enhancing therapeutic effects. By attaching targeting molecules, these nanostructures can recognize and bind to cancer cells, increasing treatment precision. This approach offers tailored solutions for targeted drug delivery, enabling the delivery of multiple drugs in a coordinated manner. This review explores the advancements and applications of DNA nanostructures in cancer treatment, with a focus on targeted drug delivery and multi-drug therapy. It discusses the benefits and current limitations of nanoscale formulations in cancer therapy, categorizing DNA nanostructures into pure forms and hybrid versions optimized for drug delivery. Furthermore, the review examines ongoing research efforts and translational possibilities, along with challenges in clinical integration. By highlighting the advancements in DNA nanostructures, this review aims to underscore their potential in improving cancer treatment outcomes.

A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells.

For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models. Here, a multifunctional nanostructured hydrogel is presented as a 2D platform to investigate how the interdependencies of cytokine binding and nanopatterned adhesive ligands influence the behavior of human hematopoietic stem and progenitor cells (HSPCs). The results indicate that the degree of HSPC polarization and motility, observed when cultured on gels presenting the chemokine SDF-1α and a nanoscale-defined density of a cellular (IDSP) or extracellular matrix (LDV) α4ß1 integrin binding motif, are differently influenced on hydrogels functionalized with the different ligand types. Further, SDF-1α promotes cell polarization but not motility. Strikingly, the degree of differentiation correlates negatively with the nanoparticle spacing, which determines ligand density, but only for the cellular-derived IDSP motif. This mechanism potentially offers a means of predictably regulating early HSC fate decisions. Consequently, the innovative multifunctional hydrogel holds promise for deciphering dynamic HSPC-niche interactions and refining transplantation therapy protocols.

Amino-Acid-Encoded Supramolecular Nanostructures for Persistent Bioluminescence Imaging of Tumor.

Bioluminescence imaging (BLI) is a powerful technique for noninvasive monitoring of biological processes and cell transplantation. Nonetheless, the application of D-luciferin, which is widely employed as a bioluminescent probe, is restricted in long-term in vivo tracking due to its short half-life. This study presents a novel approach using amino acid-encoded building blocks to accumulate and preserve luciferin within tumor cells, through a supramolecular self-assembly strategy. The building block platform called Cys(SEt)-X-CBT (CXCBT, with X representing any amino acid) utilizes a covalent-noncovalent hybrid self-assembly mechanism to generate diverse luciferin-containing nanostructures in tumor cells after glutathione reduction. These nanostructures exhibit efficient tumor-targeted delivery as well as sequence-dependent well-designed morphologies and prolonged bioluminescence performance. Among the selected amino acids (X = Glu, Lys, Leu, Phe), Cys(SEt)-Lys-CBT (CKCBT) exhibits the superior long-lasting bioluminescence signal (up to 72 h) and good biocompatibility. This study demonstrates the potential of amino-acid-encoded supramolecular self-assembly as a convenient and effective method for developing BLI probes for long-term biological tracking and disease imaging.

Functional polymeric DNA nanostructure-decorated cellulose nanocrystals for targeted and stimuli-responsive drug delivery.

Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy.

Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures.

The functionality of supramolecular nanostructures can be expanded if systems containing multiple components are designed to either self-sort or mix into coassemblies. This is critical to gain the ability to craft self-assembling materials that integrate functions, and our understanding of this process is in its early stages. In this work, we have utilized three different peptide amphiphiles with the capacity to form ß-sheets within supramolecular nanostructures and found binary systems that self-sort and others that form coassemblies. This was measured using atomic force microscopy to reveal the nanoscale morphology of assemblies and confocal laser scanning microscopy to determine the distribution of fluorescently labeled monomers. We discovered that PA assemblies with opposite supramolecular chirality self-sorted into chemically distinct nanostructures. In contrast, the PA molecules that formed a mixture of right-handed, left-handed, and flat nanostructures on their own were able to coassemble with the other PA molecules. We attribute this phenomenon to the energy barrier associated with changing the handedness of a ß-sheet twist in a coassembly of two different PA molecules. This observation could be useful for designing biomolecular nanostructures with dual bioactivity or interpenetrating networks of PA supramolecular assemblies.

DNA-based nanostructures for RNA delivery.

RNA-based therapeutics have emerged as a promising approach for the treatment of various diseases, including cancer, genetic disorders, and infectious diseases. However, the delivery of RNA molecules into target cells has been a major challenge due to their susceptibility to degradation and inefficient cellular uptake. To overcome these hurdles, DNA-based nano technology offers an unprecedented opportunity as a potential delivery platform for RNA therapeutics. Due to its excellent characteristics such as programmability and biocompatibility, these DNA-based nanostructures, composed of DNA molecules assembled into precise and programmable structures, have garnered significant attention as ideal building materials for protecting and delivering RNA payloads to the desired cellular destinations. In this review, we highlight the current progress in the design and application of three DNA-based nanostructures: DNA origami, lipid-nanoparticle (LNP) technology related to frame guided assembly (FGA), and DNA hydrogel for the delivery of RNA molecules. Their biomedical applications are briefly discussed and the challenges and future perspectives in this field are also highlighted.

Copper-Induced Supramolecular Peptide Assemblies for Multi-pathway Cell Death and Tumor Inhibition.

Although self-assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of the resultant assemblies remains an ongoing challenge. Inspired by the copper peptide naturally present in human plasma, in this study, we designed a synthetic precursor, FcGH. FcGH can self-assemble via two distinct pathways: spontaneous and Cu2+-induced. These two assembly pathways enabled the formation of assemblies with tunable morphologies by adjusting the amount of added Cu2+. We found that the nanoparticles formed by Cu2+-induced self-assembly exhibited a significantly higher cellular uptake efficiency than the wormlike fibers formed spontaneously. Moreover, this Cu2+-induced assembly process occurred spontaneously at a 1:1 molar ratio of Cu2+ to FcGH, avoiding the excessive use of Cu²âº and a tedious preparation procedure. By co-assembling with FcGH-conjugated 10-hydroxycamptothecin (HCPT), Cu2+-induced supramolecular nanodrugs elicited multiple cell death modalities in cancer cells with elevated immunogenicity, enhancing the therapeutic effect compared to free HCPT. This study highlights Cu2+-induced self-assembly as an efficient tool for directing the assembly of nanodrugs and for synergistic tumor therapy.

Colloidal carbon soot templated TiO2/Ag surface functionalized 3D printed metal brushes as new generation surface enhanced Raman scattering substrates.

This present work demonstrated the functional transformation of 3D printed metal substrates into a new family of Surface-enhanced Raman Scattering substrates, a promising approach in developing SERS-based Point-of-care (PoC) analytical platforms. l-Powder Bed Fusion (l-PBF, Additive manufacturing or 3D printing technique) printed metal substrates have rough surfaces, and exhibit high thermal stability and intrinsic chemical inertness, necessitating a suitable surface functionalization approach. This present work demonstrated a unique multi-stage approach to transform l-PBF printed metal structures as recyclable SERS substrates by colloidal carbon templating, chemical vapor deposition, and electroless plating methods sequentially. The surface of the printed metal structures was functionalized using the colloidal carbon soot particles, that were formed by the eucalyptus oil flame deposition method. These carbon particles were shown to interact with the metals present in the printed structures by forming metal carbides and function as an adlayer on the surface. Subsequent deposition of TiO2 onto these templates led to strong grafting of TiO2 and retaining the fractal structure of the soot template onto the metal surface. Electroless deposition of silver nanoparticles resulted in the formation of fractally structured TiO2/Ag nanostructures and these functionalized printed metal structures were shown as excellent SERS substrates in enhancing the vibrational spectral features of Rhodamine B (RhB). The presence of TiO2 photocatalyst on the surface was shown to remove the RhB analyte from the surface under photochemical conditions, which enables the regeneration of SERS activity, and the substrate can be recycled. The migration of metals from the printed metal structures into the fractally ordered TiO2/Ag nanostructures was found to enhance the photocatalytic activity and increase the recyclability of these substrates. This study demonstrates the potential of 3D-printed Inconel metal substrates as next-generation recyclable SERS platforms, offering a substantial advancement over traditional colloidal, thin-film, flexible, and hard SERS substrates.

Advances in inorganic nanoparticles-based drug delivery in targeted breast cancer theranostics.

Theranostic nanoparticles (NPs) have the potential to dramatically improve cancer management by providing personalized medicine. Inorganic NPs have attracted widespread interest from academic and industrial communities because of their unique physicochemical properties (including magnetic, thermal, and catalytic performance) and excellent functions with functional surface modifications or component dopants (e.g., imaging and controlled release of drugs). To date, only a restricted number of inorganic NPs are deciphered into clinical practice. This review highlights the recent advances of inorganic NPs in breast cancer therapy. We believe that this review can provides various approaches for investigating and developing inorganic NPs as promising compounds in the future prospects of applications in breast cancer treatment and material science.

Unveiling the potential of graphene and S-doped graphene nanostructures for toxic gas sensing and solar sensitizer cell devices: insights from DFT calculations.

CONTEXT: In this work, we explore the potential of 2D materials, particularly graphene and its derivatives, for eco-friendly electricity generation and air pollution reduction. Leveraging the significant surface area of graphene nanomaterials, the susceptibility of these graphene-based nanostructures to hazardous substances and their applicability in clean solar cell (SSC) devices were systematically investigated using density functional theory (DFT), as implemented within Gaussian 5.0 code. Time-dependent DFT (TD-DFT) was employed to characterize the UV-visible spectrum of unstrained nanostructures. Herein, we considered three potentially harmful gases-CO, NH3, and Br2. Adsorption calculations revealed a notable interaction between the pure graphene nanostructure and Br2 gas, while the S-doped counterpart exhibited reduced interaction. Saturated S-doped nanostructures demonstrated an enhanced affinity for NH3 and CO gases compared to their pure S-doped counterparts, attributed to the sulfur (S) atom facilitating gas molecule binding to the nanostructure's surface. Furthermore, simulations of the SSC device architecture indicated the superior performance of the pure graphene nanostructure in terms of light-harvesting efficiency, injection energy, and electron injection into the lower conduction band of CBM titanium dioxide (TiO2). These findings suggest a potential avenue for developing nanostructures tailored for SSC devices and gas sensors, offering a dual solution to address air pollution concerns. METHODS: Density function theory was used to compute the ground and excited state properties for pure and sulfur-doped graphene nanostructures. The hybrid function B3LYP with a 6-31G* basis set was utilized to describe the exchange correlation. Gauss Sum 2.2 software is used to estimate the density of state (DOS) for all structures under investigation.

Targeting HIF-1α with Specific DNA Yokes for Effective Anticancer Therapy.

Hypoxia, a ubiquitous hallmark in cancer, underscores the significance of targeting HIF-1α, the principal transcriptional factor of hypoxic responses, for effective cancer therapy. Herein, DNA yokes, a novel class of DNA nanomaterials harboring specific HIF-1α binding sequences (hypoxia response elements, HREs), are introduced as nanopharmaceuticals for cancer treatment. Comprising a basal tetrahedral DNA nanostructure and four HRE-bearing overhanging chains, DNA yokes exhibit exceptional stability and prolonged intracellular retention. The investigation reveals their capacity to bind HIF-1α, thereby disrupting its interaction with the downstream genomic DNAs and impeding transcriptional activity. Moreover, DNA yokes facilitate HIF-1α degradation via the ubiquitination pathway, thereby sequestering it from downstream targets and ultimately promoting its degradation. In addition, DNA yokes attenuate cancer cell proliferation, migration, and invasion under hypoxic conditions, while also displaying preferential accumulation within tumors, thereby inhibiting tumor growth and metastasis in vivo. This study pioneers a novel approach to cancer therapy through the development of DNA-based drugs characterized by high stability and low toxicity to normal cells, positioning DNA yokes as promising candidates for cancer treatment.

Macromolecular Nano-Assemblies for Enhancing the Effect of Oxygen-Dependent Photodynamic Therapy Against Hypoxic Tumors.

In oxygen (O2)-dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O2, and subsequently cytotoxic singlet oxygen (1O2) is generated. Therefore, the availability of O2 and the utilization efficiency of generated 1O2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1O2 resulting from its short half-life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano-assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1O2. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O2-dependent PDT against hypoxic tumors.

Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol.

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Advancements in Aptamer-Driven DNA Nanostructures for Precision Drug Delivery.

DNA nanostructures exhibit versatile geometries and possess sophisticated capabilities not found in other nanomaterials. They serve as customizable nanoplatforms for orchestrating the spatial arrangement of molecular components, such as biomolecules, antibodies, or synthetic nanomaterials. This is achieved by incorporating oligonucleotides into the design of the nanostructure. In the realm of drug delivery to cancer cells, there is a growing interest in active targeting assays to enhance efficacy and selectivity. The active targeting approach involves a "key-lock" mechanism where the carrier, through its ligand, recognizes specific receptors on tumor cells, facilitating the release of drugs. Various DNA nanostructures, including DNA origami, Tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, can traverse the lipid layer of the cell membrane, allowing cargo delivery to the nucleus. Aptamers, easily formed in vitro, are recognized for their targeted delivery capabilities due to their high selectivity for specific targets and low immunogenicity. This review provides a comprehensive overview of recent advancements in the formation and modification of aptamer-modified DNA nanostructures within drug delivery systems.

Stimulus of Work Function on Electron Transfer Process of Intermetallic Nickel-Antimonide Toward Bifunctional Electrocatalyst for Overall Water Splitting.

Engineering the intermetallic nanostructures as an effective bifunctional electrocatalyst for hydrogen and oxygen evolution reactions (HER and OER) is of great interest in green hydrogen production. However, a few non-noble metals act as bifunctional electrocatalysts, exhibiting terrific HER and OER processes reported to date. Herein the intermetallic nickel-antimonide (Ni─Sb) dendritic nanostructure via cost-effective electro-co-deposition method is designed and their bifunctional electrocatalytic property toward HER and OER is unrevealed. The designed Ni─Sb delivers a superior bifunctional activity in 1 m KOH electrolyte, with a shallow overpotential of ≈119 mV at -10 mA for HER and ≈200 mV at 50 mA for OER. The mechanism behind the excellent bifunctional property of Ni─Sb is discussed via "interfacial descriptor" with the aid of Kelvin probe force microscopy (KPFM). This study reveals the rate of electrocatalytic reaction depends on the energy required for electron and proton transfer from the catalyst's surface. It is noteworthy that the assembled Ni─Sb-90 electrolyzer requires only a minuscule cell voltage of ≈1.46 V for water splitting, which is far superior to the art of commercial catalysts.

Bimetallic DNAsome Decorated with G4-DNA as a Nanozyme for Targeted and Enhanced Chemo/Chemodynamic Cancer Therapy.

Cancer is indisputably one of the major threats to mankind, and hence the design of new approaches for the improvement of existing therapeutic strategies is always wanted. Herein, the design of a tumor microenvironment-responsive, DNA-based chemodynamic therapy (CDT) nanoagent with dual Fenton reaction centers for targeted cancer therapy is reported. Self-assembly of DNA amphiphile containing copper complex as the hydrophobic Fenton reaction center results in the formation of CDT-active DNAsome with Cu2+-based Fenton catalytic site as the hydrophobic core and hydrophilic ssDNA protrude on the surface. DNA-based surface addressability of the DNAsome is then used for the integration of second Fenton reaction center, which is a peroxidase-mimicking DNAzyme noncovalently loaded with Hemin and Doxorubicin, via DNA hybridization to give a CDT agent having dual Fenton reaction centers. Targeted internalization of the CDT nanoagent and selective generation of •OH inside HeLa cell are also shown. Excellent therapeutic efficiency is observed for the CDT nanoagent both in vitro and in vivo, and the enhanced efficacy is attributed to the combined and synergetic action of CDT and chemotherapy.

Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing.

Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin's effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.

Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres (100-300 nm in size) loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than non-specific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study reveals the potential for anti-cancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labeling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier allowing for the precise targeting of tumors. This combination has the potential to produce anti-tumor effects in the active targeted therapy of GBM.

Design and fabrication of alginate hydrogel nanohybrid as a promising cancer treatment.

Objectives: Basal cell carcinoma (BCC) is the most common form of skin cancer and the most frequently occurring form of all cancers, affecting sun-exposed areas like the face. Surgery is the main treatment, focusing on safe and minimally invasive methods for better outcomes. Technology has enabled the development of artificial skin substitutes for tissue repair. Tissue engineering uses scaffolds to create functional replacements. This project aims to create an alginate-based hydrogel with PEG-coated gold nanoparticles. Materials and Methods: The project extensively explored the modification of alginate hydrogels with PEG-coated gold nanoparticles, involving the synthesis of gold nanoparticles, their integration with the polymer, and the subsequent preparation of the concentrated hybrid hydrogel. Utilizing various physicochemical techniques, such as UV-visible spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy, the fabrication process was optimized and characterized. Results: The successful synthesis of the hybrid biomaterial was achieved through robust and highly reproducible methods. The MTT assay results offered valuable insights into the biocompatibility and safety of the PEG-coated gold nanoparticle-loaded alginate-based films. The incorporation of PEG-coated gold nanoparticles allowed for potential drug loading on the nanoparticle surface and, consequently, within the hydrogel. Cellular assays were conducted to assess the potential applications of this novel biomaterial. Conclusion: The addition of polyethylene glycol made it possible to load different drugs onto the gold nanoparticles and also within the hydrogel. This makes it a promising choice for potential uses in tissue engineering.

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy.

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.