ACS Applied Bio Materials最新文献

Development of nanoplatforms with in situ activation for chemotherapy represents a promising modality for biomedical application. Herein, a multifunctional nanoplatform, CMS@DTC@PDA@RuNO@FA (abbreviated as CDPNF NPs), was developed for highly efficient antitumor therapy, in which diethyldithiocarbamate (DTC)-loaded mesoporous Cu₂MoS₄ (CMS) nanoparticles were covered by polydopamine (PDA) layers and further covalently modified with a NO donor (RuNO) and a folic acid (FA)-directing moiety. Under the mild acidic tumor microenvironment (TME), the CDPNF NPs co-liberated DTC and Cu²⁺ in the tumor site, where in situ formation of the highly cytotoxic Cu(DTC)₂ complex effectively killed tumor cells. Furthermore, under near-infrared (NIR) light irradiation, the CDPNF NPs could deliver nitric oxide (NO) and produce superoxide anions (O₂^•-), followed by the formation of more toxic peroxynitrite (ONOO^-), which led to promoted cell apoptosis. Under 1064 nm NIR light irradiation, in vivo experiments with CDPNF NPs demonstrated an impressively high tumor inhibition rate (∼97%) while with good biocompatibility. This work represents an in situ activated approach for precision medicine that might imply its promising potential for clinical applications.

We developed two deep-red cyanine chromophores, probes A and B, for selective mitochondrial NAD(P)H detection in live cells. Probe A features a 1,2,3,3-tetramethyl-3H-indolium core, while probe B incorporates a 1,1,2,3-tetramethyl-1H-benzo[e]indol-3-ium moiety, both linked to quinolinium via a vinyl bond to enable fluorescence modulation upon NAD(P)H reduction of probes A and B. To explore the role of electron-withdrawing groups in probe sensitivity, we synthesized three additional cyanine dyes (probes C, D, and E) via condensation of 6-quinolinecarboxaldehyde with 2,3-dimethyl-1,3-benzothiazolium acceptor and malononitrile derivatives, followed by methylation. Under NAD(P)H-deficient conditions, probe A showed absorption at 382 nm with weak fluorescence at 636 nm, while probe B absorbed at 443 nm with weak fluorescence at 618 nm. Upon NAD(P)H reduction, probe A exhibited red-shifted absorption at 520 nm with enhanced emission at 589 nm, and probe B at 550 nm with strong emission at 610 nm. Probe C showed absorption at 524 nm with enhanced emission at 586 nm, while probes D and E exhibited no detectable NAD(P)H response, highlighting the critical role of quinolinium acceptors. Probe B demonstrated superior sensitivity, successfully tracking NAD(P)H fluctuations in HeLa cells under glycolysis stimulation (glucose, lactate, pyruvate) and treatments with LPS and methotrexate. It also visualized NAD(P)H in Drosophila larvae, revealing increased levels after drug treatments. Notably, probe B distinguished between healthy and diseased human kidney tissues, detecting significantly elevated NADH levels in autosomal dominant polycystic kidney disease (ADPKD) samples, emphasizing its diagnostic potential. This study introduces probe B as a versatile and reliable NAD(P)H sensor for metabolic research and disease diagnostics, offering valuable insights into redox processes in live cells, organisms, and clinical samples.

Hemoglobin shows different contrasts on magnetic resonance imaging (MRI) depending on the iron and oxygenation states of heme. Functional brain MRI utilizes the differences in the concentrations of oxyhemoglobin and deoxyhemoglobin in cerebral blood vessels; blood clots produce strong magnetic susceptibility effects. We hypothesized that methemoglobin (MetHb)-based nanoparticles can act as MRI contrast agents because MetHb levels in red blood cells affect relaxivity and are strictly regulated to <1% in the blood. Herein, we describe the synthesis of methemoglobin-encapsulated liposomes (Met-HbVs) as contrast agents for MRI. Met-HbV, with a size of approximately 200 nm, increased longitudinal relaxivity (r₁) by 2.44-fold compared with hemoglobin-encapsulated liposomes in vitro. In contrast, the transverse relaxation capacity (r₂) of Met-HbVs was similar to that of the hemoglobin-encapsulated liposomes. Owing to its relaxivity, Met-HbV enhanced the signal intensity on T1-weighted images and angiography, especially in the veins. Furthermore, deleterious biological responses were seldom observed after Met-HbV administration in mice with chronic renal failure. In conclusion, Met-HbV possesses potential as a vascular contrast agent in MRI for angiography, with advantages over gadolinium-based contrast agents in terms of safety for patients with renal failure. To the best of our knowledge, this is the first report demonstrating the potential of MetHb as a biomaterial for contrast agents in MRI.

Despite advances in surgical techniques for tendon injuries and improvements in rehabilitation, the challenge of achieving sufficient tendon regeneration and preventing postoperative tissue adhesions persists for orthopedic surgeons. In this study, we developed a multilayer film with a platelet-derived growth factor-BB (PDGF-BB)-immobilized leaf-stacked structure (LSS) layer (bioactive layer) and an alginate layer (antiadhesive layer) on both sides of a PCL film (PDGF/FLSS-Alg). The porous LSS layer on the PCL film was fabricated using a heating-cooling method with tetraglycol, where PDGF-BB was adsorbed onto the LSS layer. An alginate coating was applied on the opposite side to form the antiadhesion layer. The PDGF-BB loaded on the LSS layer provided a sustained release at effective concentrations for over 29 days. From in vitro cell culture and in vivo animal studies, the alginate layer proved effective in preventing cell/tissue adhesion; meanwhile, the bioactive layer facilitated tenogenic differentiation in hBMSCs and supported tendon regeneration. Accordingly, we propose that PDGF/FLSS-Alg offers a viable strategy for effective tendon regeneration in clinical practice.

Injectable hydrogels represent a highly promising approach for localized drug delivery systems (DDSs) in the management of bone-related conditions such as osteoporosis, osteonecrosis, osteoarthritis, osteomyelitis, and osteosarcoma. Their appeal lies in their biocompatibility, adjustable mechanical properties, and capacity to respond to external stimuli, including pH, temperature, light, redox potential, ionic strength, and enzymatic activity. These features enable enhanced targeted delivery of bioactive agents. This mini-review evaluates the synthesis of injectable hydrogels as well as recent advancements for treating a range of bone disorders, focusing on their mechanisms as localized and sustained DDSs for delivering drugs, nanoparticles, growth factors, and cells (e.g., stem cells). Moreover, it highlights their clinical studies for bone disease treatment. Additionally, it emphasizes the potential synergy between injectable hydrogels and hydrogel-based point-of-care technologies, which are anticipated to play a pivotal role in the future of bone disease therapies. Injectable hydrogels have the potential to transform bone disease treatment by facilitating precise, sustained, and minimally invasive therapeutic delivery. Nevertheless, significant challenges, including long-term biocompatibility, scalability, reproducibility, and precise regulation of drug release kinetics, must be addressed to unlock their clinical potential fully. Addressing these challenges will not only advance bone disease therapy but also open new avenues in regenerative medicine and personalized healthcare.

The emergence of immunotherapy as a revolutionary therapeutic modality has fostered confidence and underscored its potent efficacy in tumor therapy. However, enhancing the therapeutic efficacy of immunotherapy by precise and judicious administration poses a significant challenge. In this context, we have developed a disulfide-bearing transdermal nanovaccine by integrating a thiol-reactive agent lipoic acid (LA) into a metal-coordinated cyclic dinucleotide nanoassembly, designated as LA-Mn-cGAMP (LMC) nanovaccines. Upon topical application to the skin with melanoma, the dithiolane moiety of LA enables thiol-disulfide dynamic exchange in the skin, hence facilitating penetration into both the skin and subcutaneous tumor tissues via the thiol-mediated uptake (TMU) mechanism. Our findings demonstrate that transdermal administration of LMC significantly enhances STING activation, mitigates the immunosuppressive tumor microenvironment (TME), and retards melanoma progression. Moreover, the remodeled TME amplifies the efficacy of immune checkpoint inhibitors. This advancement offers an administration strategy for existing STING agonist therapy, potentially improving the biosafety of immunotherapy.

Interferon-gamma (IFN-γ), an essential inflammatory cytokine, is intricately associated with a variety of fatal diseases as a key early biomarker. In this work, we designed and constructed an electrochemical aptasensor based on topological insulator Bi₂Se₃ sheets. Micron-scale Bi₂Se₃ sheets were prepared by electrochemical exfoliation from single crystals to make electrodes of the aptasensors. The unique and robust Dirac surface states of Bi₂Se₃ could enhance the charge transfer efficiency of the solid-liquid interface, improving the performance of the aptasensors. The developed aptasensor exhibits a linear response to IFN-γ concentration in the range of 1-100 pg/mL with a detection limit as low as 0.6 pg/mL, enabling it to meet the clinical requirements. The performance of the aptasensors also shows excellent stability and selectivity. Furthermore, the aptasensor was applied to human serum detection and was comparable in performance to the clinical standard enzyme-linked immunosorbent assay technique. Our work indicates that the aptasensor based on Bi₂Se₃ sheets has great potential for application in the clinical detection of IFN-γ and other possible biomarkers.

Designing advanced biomimetic nanoplatforms that combine photothermal therapy (PTT) and immune activation represents a modern approach to addressing the challenges of cancer therapy. This study presents a nanobiomimetic hollow copper-sulfide (HCuS) platform for precise homotypic tumor targeting and melanoma treatment. The HCuS@OVA@CM (COC) nanoplatform-encapsulated ovalbumin (OVA) antigen protein within HCuS nanoparticles and was coated with melanoma cell membranes (B16F10). Importantly, this design facilitates specific tumor accumulation and achieves 16.0% photothermal conversion efficiency under 1064 nm NIR-II irradiation, which is a key factor for therapeutic success. In vitro studies have demonstrated that this nanoplatform induces immunogenic cell death (ICD), enhances antigen presentation, and stimulates dendritic cell (DCs) maturation. In vivo experiments confirmed that COC-mediated NIR-II photothermal treatment significantly suppressed tumor growth without notable body weight loss. This biomimetic nanoplatform approach offers a targeted, enhanced, and effective immune response for tumor photothermal immunotherapy, making it a promising candidate for advanced melanoma treatment and anticancer therapy.

Chronic ulcers present numerous challenges in treatment such as prolonged inflammation, infections resistant to drugs, and the formation of scars. In this research, we developed a calcium ion (Ca²⁺) cross-linked alginate (Alg) hydrogel loaded with CuO nanosheet/fibroblast cells via a microfluidic system with substantial efficiency in accelerating healing and preventing infection. Initially, the soft lithography method was utilized to fabricate the microfluidic system, which was employed to produce alginate hydrogel incorporating nanosheets of copper oxide (CuO) and MEF cells. The properties of hydrogel and copper oxide nanosheets were analyzed by using FE-SEM, EDS/EDX, and elemental mapping to determine their physicochemical characteristics. The viability of mouse embryonic fibroblast cells (MEF) in alginate-CuO hydrogel was explored through cell viability assay, and the antibacterial properties were also studied using colony-forming assay. The healing abilities of the hydrogel were investigated using an excisional, full-thickness wound rat model. Our results revealed proper antimicrobial and angiogenic properties with slight cytotoxicity for CuO nanosheets at a concentration of 25 μg/mL. The alginate-CuO-cell-treated group exhibited a faster wound contraction and healing among all treatments. The results of the in vivo assay along with histology and gene expression indicate a synergistic cooperation between MEF and CuO, leading to enhanced re-epithelialization, angiogenesis, and matrix remodeling. In this research, a therapeutic hydrogel with qualities like microbicidal, angiogenic, immune system modulation, and promotion of ECM and epithelium regeneration, resulting in faster healing, was developed. Moreover, there was a synergic impact noticed between CuO nanosheets and MEF cells as well as improved formation of blood vessels and collagen accumulation. In conclusion, this biocompatible hydrogel offers a promising strategy for effective wound healing without the need for invasive procedures.

Bone regeneration is a process that aims to restore the structure and function of damaged bone tissues. Modern approaches for bone regeneration involve a combination of strategies, including tissue engineering and biomaterials, to promote healing. In this study, electrospun nanofibers were developed by using biosynthesized chitosan (CS)- and graphene oxide (GO)-loaded polyacrylonitrile (PAN) nanofibers. These scaffolds demonstrated stable mechanical support and capability to promote rapid bone defect repair. The physicochemical properties of the prepared nanoparticles and nanofibers were characterized using XRD and XPS analysis. The nanofiber morphology and structure of the CS/GO composite were analyzed through SEM and TEM. In vitro studies and ALP activity demonstrated the membranes capability to promote new bone formation and support healing, and Alizarin red staining highlighted the membrane's ability to enhance cell-cell interactions and increase calcium deposition, crucial for tissue regeneration. Cytotoxicity analysis revealed that 97.66 ± 1.5% of MG-63 cells remained viable on the surface of the prepared nanofiber, as assessed by the MTT assay. At the molecular level, real-time RT-PCR was used to examine the mRNA expression of Runx2 and type 1 collagen. Promoting osteogenic gene expression and enhancing mineral deposition on the prepared nanofiber show significant potential in accelerating bone healing and ensuring the successful integration of the scaffold with the surrounding bone tissue. Based on these findings, we conclude that the CS/GO@PAN nanofibrous membrane holds significant promise as a substrate for bone regeneration.