Intra-articular injection of modified citrus pectin and hyaluronate gel induces synergistic effects in treating osteoarthritis.

We previously found that modified citrus pectin (MCP), an inhibitor of pro-inflammatory factor Galectin-3 (Gal-3), has significant anti-inflammatory and chondroprotective effects. In this study, a hyaluronate (HA) gel-based sustained release system of MCP (MCP-HA) was developed as an anti-inflammatory agent for chronic inflammation for osteoarthritis (OA) treatment. The MCP-HA gel was injected into the knee joint cavities of OA rabbit models induced by anterior cruciate ligament transection (ACLT) or modified Hulth method once a week for five weeks. We found that MCP-HA could improve the symptoms and signs of OA, protect articular cartilage from degeneration, suppress synovial inflammation, and therefore alleviate OA progression. Proteomic analysis of the synovial fluid obtained from the knee joints of OA rabbits revealed that MCP-HA synergistically regulated the levels of multiple inflammatory mediators and proteins involved in metabolic pathways. Taken together, our results demonstrate that the MCP-HA shows a synergistic effect of HA and MCP by modulating both inflammation and metabolic processes, thereby alleviating OA progression. The MCP-HA sustained release system has promising potential for long-term use in OA treatment.

The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent.

Antibody modification is a common method for endowing drug carriers with the ability to target specific cells. Recent studies suggest that the efficacy of these antibody-modified drug carriers is closely related to their physicochemical properties, such as size, shape, stiffness, charge, and surface chemistry. In this study, we functionalized microcapsules with antibodies to investigate the combined effect of shape and stiffness on their targeting ability. We synthesized hollow microcapsules, both spherical and rod-shaped, with adjustable stiffness using calcium carbonate particles as templates and silk fibroin (SF) as the shell material. These microcapsules were then functionalized with trastuzumab (TTZ) to enhance targeting capabilities. Our analysis revealed that increasing stiffness significantly improved the specificity and avidity of TTZ-coated rod-shaped microcapsules, but not spherical ones, indicating a strong shape-dependent influence of stiffness on these properties. Additionally, we explored the mechanisms of endocytosis using various inhibitors and found that both macropinocytosis and clathrin played critical roles in the cellular uptake of microcapsules. Furthermore, we loaded microcapsules with doxorubicin (DOX) to evaluate their anti-tumor efficacy. The stiffest TTZ-coated, DOX-loaded rod-shaped microcapsules demonstrated the most potent anti-tumor effects on BT-474 cells and the highest uptake in BT-474 3D spheroids. This research contributes to the development of more effective microcapsule-based target delivery systems and the realization of the full potential of microcapsule drug delivery systems.

Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair.

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment.

Locally delivered modified citrus pectin - a galectin-3 inhibitor shows expected anti-inflammatory and unexpected regeneration-promoting effects on repair of articular cartilage defect.

Treating the concomitant inflammation in the process of injury and repair, and simultaneously promoting cartilage regeneration is very important for the repair of articular cartilage (AC) defects. Nevertheless, this remains a massive challenge. To address this issue, a collagen membrane-based modified citrus pectin (MCP) delivery system (MCP-C) was developed in this study by targeting galectin-3 (Gal-3), an upstream proinflammatory factor. As expected, MCP shows anti-inflammatory effects; it downregulates the expressions of IL-1ß, MMP13, Gal-3, and COL1A2, inhibits the degenerative effects of Gal-3 on chondrocytes in vitro, and protects chondrocytes from degeneration and death in vivo. Unexpectedly, MCP promotes the proliferation of chondrocytes, upregulates the expression of COL2A1 and SOX9 in the chondrocytes in vitro, and enhances the repair of AC defect in rabbit knee, especially MCP500-C with a complete release of the loading amount of approximately 500 µg/cm2 in a day. Mechanistically, MCP upregulates the expressions of multiple endogenous growth factors for chondrogenesis via the transcriptome sequencing of MCP-treated chondrocytes, and downregulates the expressions of various inflammatory factors. These findings demonstrate that locally delivered MCP can simultaneously modulate both regenerative and inflammatory responses, and can enhance the repair of AC defects.

The effect of blending poly (l-lactic acid) on in vivo performance of 3D-printed poly(l-lactide-co-caprolactone)/PLLA scaffolds.

Blending poly (l-lactic acid, PLLA) with poly (l-lactide-co-caprolactone, PLCL) is an effective strategy for developing new PLCL/PLLA blend based biomaterials. However, the effect of PLLA on in vivo performance of PLCL/PLLA blends is unclear yet. To address this issue, in this study, the effect of PLLA on in vivo biodegradability and biocompatibility of 3D-printed scaffolds of PLCL/PLLA blend was investigated. Three kinds of different 3D-printed PLCL/PLLA scaffolds using different blends with different mass ratios of the polymers, were prepared and implanted subcutaneously. The shrinkage and tissue responses were monitored by ultrasonography after the implantation. 2 months post-operation, the in vivo performances of the scaffolds were investigated histologically. All scaffolds showed good biocompatibility and allowed fast tissues ingrowth, however PLCL50/PLLA50 scaffold with the highest PLLA ratio induced the thickest the fibrous capsule surrounding the scaffolds and highest inflammatory scores. Furthermore, it was found that the fine porous structures of all scaffolds were well maintained, indicating the 3D-printed scaffolds were degraded through a surface erosion but not bulk erosion way. However, different scaffolds showed different shrinkage and degradation ratios, and PLCL50/PLLA50 scaffold resulted in a significant shrinkage, while PLCL90/PLLA10 scaffold showed the better structural stability. Therefore, PLLA at blending different ratio had different effects on the in vivo performance of 3D-printed PLCL/PLLA scaffolds. Particularly, PLCL/PLLA scaffolds blending with low ratio of PLLA, such as PLCL90/PLLA10 scaffold showed better application potential in tissue engineering. Our findings provide a new insight on the rational design, constrcution and application of the 3D-printed PLCL/PLLA scaffolds.

Rational engineering of biomimetic flavylium fluorophores for regulating the lysosomal and mitochondrial localization behavior by pH-induced structure switch and application to fluorescence imaging.

Mitochondria and lysosomes, as the important subcellular organelles, play vital roles in cell metabolism and physiopathology. However, there is still no general method to precisely regulate the lysosomal and mitochondrial localization behavior of fluorescent probes except by selecting specific targeting groups. Herein, we proposed a pH-induced structure switch (pHISS) strategy to solve this tricky puzzle. For the proof-of-concept, we have rationally designed and synthesized a series of cationic flavylium derivatives FL-1-9 with tunable pH-induced structure switch through adjusting the electron-donating ability of the substituents. As expected, the co-localization imaging experiments revealed that the lysosomal and mitochondrial localization behavior of FL-1-9 dyes is closely related to their pHISS ability. It is noteworthy that FL cationic dyes with strong electron-donors are not prone to pHISS and can be well enriched in mitochondria, while FL cationic dyes with weak electron-donors are highly susceptible to pHISS and display an unusual lysosome-targeting capability. This also provided a feasible strategy for lysosomal localization without basic groups and presented new application options for some flavylium dyes previously thought to be less stable. Furthermore, FL cationic dyes with medium electron-donor exhibit certain localization abilities both in mitochondria and lysosomes. Finally, through a detailed study of pH-induced structure switch and exploiting the pH inertia brought by the strong electron-donors, a novel NIR ratiometric fluorescent probe with large wavelength-shift was constructed for monitoring mitochondrial H2S in living cells, tumor tissues and living mice, highlighting the value of the pHISS strategy in precisely regulating organelle targeting and constructing corresponding organelle targeting probes.

Three-Dimensional Printing Self-Healing Dynamic/Photocrosslinking Gelatin-Hyaluronic Acid Double-Network Hydrogel for Tissue Engineering.

Three-dimensional (3D) printing technology has great potential for constructing structurally and functionally complex scaffold materials for tissue engineering. Bio-inks are a critical part of 3D printing for this purpose. In this study, based on dynamic hydrazone-crosslinked hyaluronic acid (HA-HYD) and photocrosslinked gelatin methacrylate (GelMA), a double-network (DN) hydrogel with significantly enhanced mechanical strength, self-healing, and shear-thinning properties was developed as a printable hydrogel bio-ink for extrusion-based 3D printing. Owing to shear thinning, the DN hydrogel bio-inks could be extruded to form uniform filaments, which were printed layer by layer to fabricate the scaffolds. The self-healing performance of the filaments and photocrosslinking of GelMA worked together to obtain an integrated and stable printed structure with high mechanical strength. The in vitro cytocompatibility assay showed that the DN hydrogel printed scaffolds supported the survival and proliferation of bone marrow mesenchymal stem cells. GelMA/HA-HYD DN hydrogel bio-inks with printability, good structural integrity, and biocompatibility are promising materials for 3D printing of tissue engineering scaffolds.

Biomimetic Nanocarriers Guide Extracellular ATP Homeostasis to Remodel Energy Metabolism for Activating Innate and Adaptive Immunity System.

Metabolic interventions via targeting intratumoral dysregulated metabolism pathways have shown promise in reinvigorating antitumor immunity. However, approved small molecule immunomodulators often suffer from ineffective response rates and severe off-target toxicity. ATP occupies a crucial role in energy metabolism of components that form the tumor microenvironment (TME) and influences cancer immunosurveillance. Here, a nanocarrier-assisted immunometabolic therapy strategy that targets the ATP-adenosine axis for metabolic reprogramming of TME is reported. An ecto-enzyme (CD39) antagonist POM1 and AMP-activated protein kinase (AMPK) agonist metformin are both encapsulated into cancer cell-derived exosomes and used as nanocarriers for tumor targeting delivery. This method increases the level of pro-inflammatory extracellular ATP (eATP) while preventing the accumulation of immunosuppressive adenosine and alleviating hypoxia. Elevated eATP triggers the activation of P2X7-NLRP3-inflammasome to drive macrophage pyroptosis, potentiates the maturation and antigen capacity of dendritic cells (DCs) to enhance the cytotoxic function of T cells and natural killer (NK) cells. As a result, synergistic antitumor immune responses are initiated to suppress tumor progress, inhibit tumor distant metastases, provide long-term immune memory that offers protection against tumor recurrence and overcome anti-PD1 resistance. Overall, this study provides an innovative strategy to advance eATP-driven antitumor immunity in cancer therapy.

Design of a UCST Polymer with Strong Hydrogen Bonds and Reactive Moieties for Facile Polymer-Protein Hybridization.

Polymer-protein hybrids have been extensively used in biomedical fields. Polymers with upper critical solution temperature (UCST) behaviors can form a hydrated coacervate phase below the cloud point (Tcp), providing themselves the opportunity to directly capture hydrophilic proteins and form hybrids in aqueous solutions. However, it is always a challenge to obtain a UCST polymer that could aggregate at a high temperature at a relatively low concentration and also efficiently bind with proteins. In this work, a UCST polymer reactive with proteins was designed, and its temperature responsiveness and protein-capture ability were investigated in detail. The polymer was synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylamide (AAm) and N-acryloxysuccinimide (NAS). Interestingly, taking advantage of the partial hydrolysis of NAS into acrylic acid (AAc), the obtained P(AAm-co-NAS-co-AAc) polymer exhibited an excellent UCST behavior and possessed good protein-capture ability. It showed a relatively higher Tcp (81 °C) at a lower concentration (0.1 wt %) and quickly formed polymer-protein hybrids with high protein loading and without losing protein bioactivity, and both the polymer and polymer-protein nanoparticles showed good cytocompatibility. All the findings are attributed to the unique structure of the polymer, which provided not only the strong and stable hydrogen bonds but also the quick and mild reactivity. The work offers an easy and mild strategy for polymer-protein hybridization directly in aqueous solutions, which may find applications in biomedical fields.

Blending with Poly(l-lactic acid) Improves the Printability of Poly(l-lactide-co-caprolactone) and Enhances the Potential Application in Cartilage Tissue Engineering.

Poly(l-lactide-co-caprolactone) (PLCL, 50:50) has been used in cartilage tissue engineering because of its high elasticity. However, its mechanical properties, including its rigidity and viscoelasticity, must be improved for compatibility with native cartilage. In this study, a set of PLCL/poly(l-lactic acid) (PLLA) blends was prepared by blending with different mass ratios of PLLA that range from 10 to 50%, using thermoplastic techniques. After testing the properties of these PLCL/PLLA blends, they were used to fabricate scaffolds by the 3D printing technology. The structures and viscoelastic behavior of the PLCL/PLLA scaffolds were determined, and then, the potential application of the scaffolds in cartilage tissue engineering was evaluated by chondrocytes culture. All blends demonstrate good thermal stability for the 3D printing technology. All blends show good toughness, while the rigidity of PLCL is increased through PLLA blending, and Young's modulus of blends with 10-20% PLLA is similar to that of native cartilage. Furthermore, blending with PLLA improves the processability of PLCL for 3D printing, and the compression modulus and viscoelasticity of 3D-printed PLCL/PLLA scaffolds are different from that of PLCL. Additionally, the stress relaxation time (t 1/2) of the PLCL/PLLA scaffolds, which is important for chondrogenesis, is dramatically shortened compared with the pure PLCL scaffold at the same 3D-printing filling rate. Consistently, the PLCL90PLLA10 scaffold at a 70% filling rate with much shorter t 1/2 is more conducive to the proliferation and chondrogenesis of in vitro seeded chondrocytes accompanied by upregulated expression of SOX9 than the PLCL scaffold. Taken together, these results demonstrate that blending with PLLA improves the printability of PLCL and enhances its potential application, particularly PLCL/PLLA scaffolds with a low ratio of PLLA, in cartilage tissue engineering.

A Gelatin-Hyaluronic Acid Double Cross-Linked Hydrogel for Regulating the Growth and Dual Dimensional Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells.

Owing to its unique physiochemical properties similar to the extracellular matrix (ECM), three-dimensional (3D) crosslinked hydrogels are widely studied materials for tissue engineering. In this study, to mimic the ECM microenvironment, a two-step covalent cross-linking with hyaluronic acid and gelatin was performed to form an interpenetrating polymer network structure. Gelatin as the first network greatly improved the mechanical strength of the hydrogels, while a hyaluronic acid network as the second network improved the tenacity and biological activity. Compared with a single network hydrogel, the interpenetrating hydrogel system can further regulate the mechanical properties of the hydrogel by adjusting the ratio of the two components, thereby changing the proliferation, activity, and direction of cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). Not only that, with two culture methods for BMSCs on the surface and 3D wrapped in the double cross-linked hydrogels, they exhibited their potential to induce BMSCs to cartilage differentiation under the condition of 3D encapsulation of BMSCs and contact with BMSCs on its surface. As a scaffold material for cartilage tissue engineering, this double cross-linked hydrogel demonstrated its high feasibility and applicability in delivering BMSCs in vivo and repairing defects.

Non-mulberry silk fiber-based scaffolds reinforced by PLLA porous microspheres for auricular cartilage: An in vitro study.

Designing clinical applicable polymeric composite scaffolds for auricular cartilage tissue engineering requires appropriate mechanical strength and biological characteristics. In this study, silk fiber-based scaffolds co-reinforced with poly-L-lactic acid porous microspheres (PLLA PMs) combined with either Bombyx mori (Bm) or Antheraea pernyi (Ap) silk fibers were fabricated as inspired by the "steel bars reinforced concrete" structure in architecture and their chondrogenic functions were also investigated. We found that the Ap silk fiber-based scaffolds reinforced by PLLA PMs (MAF) exhibited superior physical properties (the mechanical properties in particular) as compared to the Bm silk fiber-based scaffolds reinforced by PLLA PMs (MBF). Furthermore, in vitro evaluation of chondrogenic potential showed that the MAF provided better cell adhesion, viability, proliferation and GAG secretion than the MBF. Therefore, the MAF are promising in auricular cartilage tissue engineering and relevant plastic surgery-related applications.

Hyaluronic Acid Hydrogel with Adjustable Stiffness for Mesenchymal Stem Cell 3D Culture via Related Molecular Mechanisms to Maintain Stemness and Induce Cartilage Differentiation.

The stemness and differentiation characteristics of bone marrow mesenchymal stem cells (BMSCs) in three-dimensional (3D) culture are of great significance for stem cell therapy and cartilage tissue engineering repair. Moreover, due to their mechanical sensitivity, scaffold materials play important roles in various cell behaviors in 3D culture. In this study, the mechanical strength of hydrogel scaffolds was adjusted by changing the molecular weight of hyaluronic acid (HA). It was proven that BMSCs in a low-strength hydrogel could maintain stemness properties by activating the Wnt/ß-catenin pathway for 1 week, while the high-molecular-weight hydrogel with a higher mechanical strength had the potential to promote the direction of cartilage differentiation of BMSCs by opening transient receptor potential vanilloid 4 (TRPV4)/Ca2+ molecular channels, also increasing the expression of type II collagen and SOX9 in BMSCs. This research has a certain reference value for the design of biomaterials for BMSCs' delivery in vivo, as well as the formulation of cartilage repair drug delivery programs based on molecular mechanisms.

A collagen mimetic peptide-modified hyaluronic acid hydrogel system with enzymatically mediated degradation for mesenchymal stem cell differentiation.

We have successfully designed and synthesized a biomimetic hydrogel system with maleimide-modified hyaluronic acid (HA) as the backbone and conjugated it to the collagen mimetic peptide (GPO)8-CG-RGDS. The matrix metalloproteinase (MMP)-sensitive peptide GCRDGPQGI↓WGQDRCG was the cross-linker. HA has high biocompatibility, low immunogenicity, and the capacity to interact with extracellular molecules. Recent studies have found that matrix metalloproteinases (MMPs) are involved in regulating the differentiation of bone mesenchymal stem cells and play a pivotal role in cartilage formation. (GPO)8-CG-RGDS has a natural collagen partial structure that follows the (Gly-Xaa-Yaa)n sequence, which is controllable in quality and can mimic the structure and biological activity of natural collagen. We found that combining this CMP with a MMP-sensitive peptide may have the potential to induce the differentiation of BMSCs into cartilage and inhibit the hypertrophic phenotype during differentiation. This design allows HA hydrogels to not only bind RGD sequences but also graft other functional peptide sequences to achieve a highly flexible platform with potential for multiple biomedical applications.

Silk fibroin/collagen/hyaluronic acid scaffold incorporating pilose antler polypeptides microspheres for cartilage tissue engineering.

A silk fibroin/collagen/hyaluronic acid (SF/COL/HA) composite scaffold was prepared via admixing, crosslinking, and lyophilizing processes. We studied its physicochemical and biological properties, such as water absorption, porosity, weight loss, and biocompatibility. The optimal ratio of SF/COL/HA scaffold was 3:6.5:0.5. Then, the optimal ratio of scaffold incorporating pilose antler polypeptides (PAPs)-PLGA microspheres was prepared, and their compatibility was studied. PAP-SF/COL/HA scaffold had favorable adhesion and proliferation. A rabbit cartilage defect model was established. The repair effect of cartilage defects was observed and evaluated among PAP-SF/COL/HA, SF/COL/HA, and sham operation groups. The defects were almost completely repaired after 13 weeks in the PAP-SF/COL/HA group, thereby indicating that the PAP-SF/COL/HA composite had a favorable effect on articular cartilage repair.

Stability, Pharmacokinetics, Biodistribution and Safety Assessment of Folate-Conjugated Pullulan Acetate Nanoparticles as Cervical Cancer Targeted Drug Carriers.

It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.

Anti-tumor drug delivery system based on cyclodextrin-containing pH-responsive star polymer: in vitro and in vivo evaluation.

A cyclodextrin-containing pH-responsive star polymer, with cyclodextrin polymer and pH-sensitive poly(2-(dimethylamino)ethyl methacrylate) as the core and poly(ethylene glycol) as the arm, was evaluated as drug carriers in vitro and in vivo. Doxorubicin (DOX) was successfully loaded into the star polymer to form nanoparticles (DOX-NPs) via host-guest interaction. The physicochemical properties such as drug loading content, size, morphology, stability and physical state of DOX-NPs were characterized in detail by (1)H NMR, DLS, SEM and DSC. Uniform and stable DOX-NPs with high encapsulation efficiency of 77.1% were obtained, and they also exhibited sustainable and controllable release of DOX in vitro. The cellular uptake of DOX-NPs was in concentration-, time- and cell type-dependent manners, and the cytotoxicity of DOX-NPs was significantly high toward HeLa and HepG2 cancer cells. Furthermore, in vivo anti-tumor experiment on BALB/c mice bearing cervical tumor showed that DOX-NPs could effectively suppress the growth of tumor without significant side effect. These findings suggest that the cyclodextrin-containing pH-responsive star polymer has a promising potential in developing novel drug delivery system for cancer therapy.

[Study of collagen mimetic peptide's triple-helix structure and its thermostability by circular dichroism].

In the present study, the authors explore the triple-helix conformation and thermal stability of collagen mimetic peptides (CMPs) as a function of peptide sequence and/or chain length by circular dichroism(CD). Five CMPs were designed and synthetized varying the number of POG triplets or incorporating an integrin alpha2beta1 binding motif Gly-Phe-Hyp-Gly-Glu-Arg (GFOGER). CD spectroscopy from 260 to 190 nm was recorded to confirm the existence of triple-helix conformation at room temperature, while thermal melting and thermal annealing of triple-helix (thermal unfolding and refolding of triple-helix, respectively) was characterized by monitoring ellipticity at 225 nm as a function of temperature. The results demonstrated that all the CMPs adopted triple-helix conformation, and the thermal stability of the CMPs was enhanced with increasing the number of POG triplets. In contrast to natural collagen, the thermal denaturation processes of CMPs were reversible, i. e. the triple-helix unfolded upon heating while refolded upon cooling. Meanwhile, the phenomenon of "hysteresis" was observed by comparing melting and thermal curves. These findings add new insights to the mechanisms of collagen and CMPs assembly, as well as provide an alternative approach to the fabrication of artificial collagen-likes biomaterials.

Chitosan-coated gold nanorods for cancer therapy combining chemical and photothermal effects.

To develop a novel type of nanoparticle for cancer therapy, gold nanorods (GNRs) are coated with chitosan (CS) derivatives to combine chemical and photothermal effects. Thiol-modified chitosan derivatives chemically conjugated to doxorubicin (DOX) are successfully synthesized and their in vitro effect is evaluated. Functional nanocarriers (DOX-CS-GNR) with good biocompatibility and optical properties are prepared by conjugating chitosan derivatives to GNRs. Two types of structures with different molar ratios of chitosan derivatives and GNRs are successfully obtained. In in vitro studies, GNR-loaded nanoparticles show low cytotoxicity and high potential for anti-cancer effects. Under conditions of short exposure time and low light intensity, DOX-CS-GNR nanocarriers with a side-by-side structure exhibit cytoxicity against tumor cells based on a combination of chemical and photothermal therapeutic effects.