Multifunctional Nanoplatform Research Articles

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 μg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

Recent advances in biomedical applications of carbon and graphene quantum dots: A review.

The carbon-based nanostructures have led to the development of theranostic nanoplatforms for simultaneous diagnosis and therapy due to their effective cell membrane-penetration ability, low degree of cytotoxicity, excellent pore volume, substantial chemical stability, and reactive surface. In the last few years, extensive efforts were made to design multifunctional nanoplatform strategies based on carbon nanostructures, involving multimodal imaging, controlled drug release capabilities, sensing in vitro, efficient drug loading capacity, and therapy. Carbon and graphene quantum dots (CQDs and GQDs) were the recent entrants, contingently being assessed for drug delivery and bioimaging. With the advancements, these quantum dots have ignited remarkable research interest and are now widely evaluated for diagnosis, bioimaging, sensing, and drug delivery applications. The last decade has witnessed their remarkable electrical, optical, and biocompatible properties since their inception. It is presumed that both of them have high potential as drug carriers and would serve as the next generation of approaches to address numerous unresolved therapeutic challenges. This review examined the recent advances of CQD and GQD based drug delivery applications, challenges, and future perspectives to pave the way for further studies in the future.

IRGD-modified erythrocyte membrane biomimetic temozolomide nanodots for the treatment of glioblastoma

The crossing of the blood-brain barrier (BBB) for conventional anticancer drugs is still a big challenge in treating glioma. The biomimetic nanoparticle delivery system has attracted increasing attention and has a promising future for crossing the BBB. Herein, we construct a multifunctional biomimetic nanoplatform using the erythrocyte membrane (EM) with the tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) as a delivery, and the inner core loaded with the chemotherapeutic drug temozolomide (TMZ). The resulting biomimetic nanoparticle has perfect biocompatibility and stealth ability, which will provide more chances to escape the reticuloendothelial system (RES) entrapment, and increase the opportunity to enter the tumor site. Moreover, the decorated iRGD has been extensively used to actively targeting and deliver therapeutic agents across the BBB into glioma tissue. We show that this biomimetic delivery of TMZ with a diameter of 22 nm efficiently slowed the growth of glioblastoma multiforme (GBM) and increased the survival rate of the 30 d from 0% to 100%.

Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

BackgroundBased on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment.MethodsGold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Iren-AuSiO2_COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Iren-AuSiO2_Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models.ResultsWe show efficient capability of Iren-AuSiO2_Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR+ tumor/PDGFRβ+ stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors.ConclusionsOur study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.

Samarium doped carbon dots for near-infrared photo-therapy

Photo-assisted tumor therapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered considerable attention as a promising approach for tumor treatment owing to its stimuli-responsive nature and noninvasive characteristics. Carbon dots (CDs) have recently emerged as a novel type of nanomaterial with great potential in the field of anticancer therapy. However, the development of multifunctional CDs nano-platforms that integrate multiple therapeutic performance remains a challenge, especially in near-infrared (NIR) window. In this study, we synthesized samarium-doped carbon dots (Sm/CDs) via a one-step hydrothermal process for fluorescence imaging guided PTT/PDT in NIR-II window. Sm/CDs demonstrated remarkable absorption and emission properties in the NIR region, enabling efficient generation of heat energy, superoxide (•O2–) and hydroxyl radicals (•OH) under NIR irradiation. The photothermal conversion efficiencies of Sm/CDs reached up to 34.12 % and 24.38 % when exposed to 808 nm and 1060 nm wavelengths, respectively. Moreover, long-term toxicity experiments conducted in vivo as well as fluorescence experiments confirmed the potential of such functional CDs for fluorescence imaging and excellent biocompatibility. It is noteworthy that the tumor is nearly eradicated when exposed to either 808 nm or 1060 nm, demonstrating significant efficacy in both scenarios. This study provides a multifunctional CDs nano-platform that offers a promising bimodal phototherapeutic strategy to enhance the synergistic treatment of tumors through PDT and PTT.

Near-infrared II theranostic agents for the diagnosis and treatment of Alzheimer's disease.

Near-infrared II theranostic agents have gained great momentum in the research field of AD owing tothe appealing advantages. Recently, an array of activatable NIR-II fluorescence probes has been developed tospecifically monitor pathological targets of AD. Furthermore, various NIR-II-mediated nanomaterials with desirablephotothermal and photodynamic properties have demonstrated favorable outcomes in the management of AD. We summerized amounts of references and focused on small-molecule probes, nanomaterials,photothermal therapy, and photodynamic therapy based on NIR-II fluorescent imaging for the diagnosis andtreatment in AD. In addition, design strategies for NIR-II-triggered theranostics targeting AD are presented, andsome prospects are also addressed. NIR-II theranostic agents including small molecular probes and nanoparticles have received theincreasing attention for biomedical applications. Meanwhile, most of the theranostic agents exhibited the promisingresults in animal studies. To our surprise, the multifunctional nanoplatforms also show a great potential in thediagnosis and treatment of AD. Although NIR-II theranostic agents showed the great potential in diagnosis and treatment of AD,there are still many challenges: 1) Faborable NIR-II fluorohpores are still lacking; 2) Biocompatibility, bioseurity anddosage of NIR-II theranostic agents should be further revealed; 3) New equipment and software associated withNIR-II imaging system should be explored.

Mitoxantrone encapsulated photosensitizer nanomicelle as carrier-free theranostic nanomedicine for near-infrared fluorescence imaging-guided chemo-photodynamic combination therapy on cancer

Combination therapy exhibits higher efficacy than any single therapy, inspiring various nanocarrier-assisted multi-drug co-delivery systems for the combined treatment of cancer. However, most nanocarriers are inert and non-therapeutic and have potential side effects. Herein, an amphiphilic polymer composed of a hydrophobic photosensitizer and hydrophilic poly(ethylene glycol) was employed as the nanocarriers and photosensitizers to encapsulate the chemotherapeutic drug mitoxantrone for chemo-photodynamic combination therapy. The resulting nanodrug consisted solely of pharmacologically active ingredients, thus avoiding potential toxicity induced by inert excipients. This multifunctional nanoplatform demonstrated significantly superior treatment performance compared to monotherapy for colorectal cancer, both in vitro and in vivo, achieving near-infrared fluorescence imaging-mediated chemo-photodynamic combined eradication of malignancy.

H2O2 self-supplying and GSH-depleting nanosystem for amplified NIR mediated-chemodynamic therapy of MRSA biofilm-associated infections

Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.

Carbon-Coated Iron Oxide Nanoparticles Promote Reductive Stress-Mediated Cytotoxic Autophagy in Drug-Induced Senescent Breast Cancer Cells.

The surface modification of magnetite nanoparticles (Fe3O4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe3O4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe3O4 NPs in situ coated by dextran (Fe3O4@Dex) and glucosamine-based amorphous carbon coating (Fe3O4@aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe3O4@aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe3O4@aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe3O4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.

Strategic Structural Control of Polyserotonin Nanoparticles and Their Application as pH-Responsive Nanomotors.

Serotonin-based nanomaterials have been positioned as promising contenders for constructing multifunctional biomedical nanoplatforms due to notable biocompatibility, advantageous charge properties, and chemical adaptability. The elaborately designed structure and morphology are significant for their applications as functional carriers. In this study, we fabricated anisotropic bowl-like mesoporous polyserotonin (PST) nanoparticles with a diameter of approximately 170 nm through nano-emulsion polymerization, employing P123/F127 as a dual-soft template and 1,3,5-trimethylbenzene (TMB) as both pore expander and emulsion template. Their formation can be attributed to the synchronized assembly of P123/F127/TMB, along with the concurrent manifestation of anisotropic nucleation and growth on the TMB emulsion droplet surface. Meanwhile, the morphology of PST nanoparticles can be regulated from sphere- to bowl-like, with a particle size distribution ranging from 432 nm to 100 nm, experiencing a transformation from a dendritic, cylindrical open mesoporous structure to an approximately non-porous structure by altering the reaction parameters. The well-defined mesopores, intrinsic asymmetry, and pH-dependent charge reversal characteristics enable the as-prepared mesoporous bowl-like PST nanoparticles' potential for constructing responsive biomedical nanomotors through incorporating some catalytic functional materials, 3.5 nm CeO2 nanoenzymes, as a demonstration. The constructed nanomotors demonstrate remarkable autonomous movement capabilities under physiological H2O2 concentrations, even at an extremely low concentration of 0.05 mM, showcasing the 51.58 body length/s velocity. Furthermore, they can also respond to physiological pH values ranging from 4.4 to 7.4, exhibiting reduced mobility with increasing pH. This charge reversal-based responsive nanomotor design utilizing PST nanoparticles holds great promise for advancing the application of nanomotors within complex biological systems.

Cucumber‐Derived Extracellular Vesicle‐Functionalized Metal‐Organic Frameworks for Enhanced Photodynamic Therapy of Hypertrophic Scars

AbstractPhotodynamic therapy (PDT) with noninvasiveness and high safety has emerged as a promising therapeutic approach for the management of hypertrophic scars (HS). However, the low transdermal delivery and overexpressed levels of intracellular glutathione (GSH) severely hinder its therapeutic effectiveness. Herein, a multifunctional biomimetic nanoplatform (NDs@EV‐RGD) composed of arginine‐glycine‐aspartic acid (RGD)‐modified cucumber‐derived extracellular vesicles (EVs) and copper‐based metal‐organic framework nanodots (Cu‐MOF NDs) is designed for PDT‐mediated HS treatment. The EVs with low Young's modulus exhibit excellent deformability which endow NDs@EV‐RGD with the capacity to overcome the compact stratum corneum barrier, thereby significantly improving their transdermal delivery efficiency. Notably, the RGD targeting peptide displays specific binding to α1β1 integrin on the fibroblast membranes within HS, leading to the high accumulation efficiency of NDs@EV‐RGD at the HS site. Under near‐infrared laser irradiation, NDs@EV‐RGD efficiently generates abundant reactive oxygen species, inducing the apoptosis of excessively proliferated fibroblasts. Moreover, Cu‐MOF NDs interact with the local GSH, leading to GSH depletion and a significant enhancement in PDT efficacy. Furthermore, NDs@EV‐RGD demonstrates a remarkable therapeutic effect in improving the appearance of HS in a rabbit ear HS model, promoting the apoptosis and remodeling of collagen fibers. Therefore, this work provides a promising biomimetic platform for HS treatment.

MnO2 nanozyme with lanthanide-based radiosensitization for advanced radiotherapy by tumor microenvironment triggering STING pathway activation

Radiotherapy, being a primary approach for cancer treatment, is plagued by systemic toxicity resulting from high-dose radiation, as well as radioresistance due to the unique characteristics of tumor microenvironment (TME), including hypoxia, high expression of reducing substances and immunosuppression. The collaboration between radiosensitization and manipulation of the TME has the potential to surmount the challenges associated with advanced radiotherapy. Here, we propose a radiosensitization approach that involves enhancing X-ray deposition through physical means, while simultaneously reducing radioresistance and activating the stimulator of interferon genes (STING) pathway using a nanozyme that mimics natural enzymatic activity. This is achieved by fabricating a lanthanide ion radiosensitizer-based multifunctional enzyme activity nanoplatform, MnO2@NaGdF4:5%Nd@NaYbF4:20%Nd(MN). In the TME, the NaGdF4:5%Nd@NaYbF4:20%Nd radiosensitizer sensitizes cancer cells to X-ray. The MnO2 exhibits catalase-like (CAT) activity, enabling it to catalyze the conversion of H2O2 into O2, thereby alleviating tumor hypoxia. Additionally, MnO2 reacts with overexpressed glutathione (GSH) by glutathione oxidase-like (GSHOx) activity to generate Mn2+ ions. This reaction optimizes the function of ·OH, which can also be produced by the released Mn2+ through a Fenton-like reaction. The DNA damage caused by ·OH can be detected by cyclic GMP-AMP synthase (cGAS) to activate STING pathway, which also can be activated by the released Mn2+ ion. Through a two-pronged strategy with radical oxygen species overproduction and STING pathway activation, the lanthanide doped radiosensitizer-based MN can be relied upon to deliver highly effective radiotherapy.

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma

BackgroundDespite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers.ResultsHerein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy.ConclusionsOur findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.Graphic

Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response.

As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy. Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions.In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated. Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration. BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.

Advancing immunotherapy in triple negative breast Cancer: A novel multimodal theranostic nanoplatform integrating synergetic ferroptosis and photothermal therapy

Triple negative breast cancer (TNBC) is a subtype of breast cancer with high invasiveness and the worst prognosis. Immunotherapy has demonstrated significant potential in its treatment. However, the response rate remains unsatisfactory. In this work, we prepared multifunctional theranostic nanoplatforms (P-R@P/U-V) with synergetic ferroptosis and photothermal therapy (PTT) in improving TNBC tumor microenvironment for improving local treatment in situ, and synergistic anti-programmed cell death-ligand 1 (PD-L1) immunotherapy to prevent distant metastasis. With P-R@P/U-V, real-time monitoring of the specific distribution in tumors is possible due to the greatly improved ultrasound imaging (US), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capabilities. Moreover, P-R@P/U-V has excellent photothermal conversion ability. Whereas PTT killed TNBC cells after laser irradiation, the liquid–gas phase transition not only improved US but also triggered controllable release of RSL3 in situ, enhancing ferroptosis of TNBC cells. Besides, the release of tumor-associated antigens (TAAs) increased via PTT and ferroptosis, strongly stimulating T cell activation, dendritic cell maturation, and anti-tumor cytokine secretion. The lung metastases of TNBC were significantly inhibited following the combined use of P-R@P/U-V and PD-L1 inhibitors. The multimodal and multifunctional nanoplatforms demonstrated excellent effects in early diagnosis and synergistic treatment of TNBC. This represents a novel strategy based on local treatment for additional enhanced anti-PD-L1 immunotherapy, with high clinical application prospects.

Golden Plasmophores with Tunable Photoluminescence and Outstanding Thermal and Photothermal Stability

AbstractAmong various hybrid nanomaterials, the combination of plasmonic nanoparticles and fluorophores in a single multifunctional nanoplatform, so‐called plasmophores, has attracted significant attention in different fields such as dark field, fluorescence, and photoacoustic imaging, biosensing, photothermal, and photodynamic therapy. Herein, author report a facile and controlled synthesis route of hybrid nanoplatforms composed of fluorescent gold nanoclusters (GNCs) coupled to plasmonic gold nanorods (GNRs) using controlled silica (SiO2) dielectric spacers of different thicknesses from now on referred to as GNR@SiO2@GNC plasmophores. The results show different degrees of plasmon‐enhanced fluorescence of the GNCs in their plasmophore hybrid system when placed at different distances from the plasmonic cores of the GNRs. On the other hand, these plasmophores show enhanced thermal stability compared to GNRs@CTAB (CTAB, cetyl trimethyl ammonium bromide). This results also demonstrated that upon annealing at elevated temperatures (800–1000 °C), the GNRs in the plasmophores are more thermally stable and robust than the GNRs@CTAB. More surprisingly, despite the commonly reported very low melting temperature of smaller‐size nanocrystals, the GNCs in the plasmophores showed high thermal stability and do not exhibit significant structural changes at elevated temperatures (800–1000 °C).

Peptide-Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy.

The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity and integration of imaging and therapeutic functions. The multifaceted nature of inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, and biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class of materials that have emerged in this context are peptide-functionalized inorganic oxide nanomaterials (PFIONs), which have demonstrated excellent performance in multifunctional imaging and therapy, making them potential candidates for advancing solid tumor diagnosis and treatment. Owing to the functionalities of peptides in tumor targeting, penetration, responsiveness, and therapy, well-designed PFIONs can specifically accumulate and release therapeutic or imaging agents at the solid tumor sites, enabling precise imaging and effective treatment. This review provides an overview of the recent advances in the use of PFIONs for the imaging and treatment of solid tumors, highlighting the superiority of imaging and therapeutic integration as well as synergistic treatment. Moreover, the review discusses the challenges and prospects of PFIONs in depth, aiming to promote the intersection of the interdisciplinary to facilitate their clinical translation and the development of personalized diagnostic and therapeutic systems by optimizing the material systems.

Hyaluronic Acid-Targeted Niosomes for Effective Breast Cancer Chemostarvation Therapy.

Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC50 values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment.

Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca2+/Cu2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu2+-tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca2+/Cu2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca2+, Cu2+, and DSF releasing simultaneously. The released Ca2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H2O2) overexpression. Meanwhile, Ca2+/reactive oxygen species-associated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)-copper complexes formed by the Cu2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu2+ will be reduced by intracellular glutathione to generate Cu+, which can catalyze the H2O2 to produce a toxic hydroxyl radical by a Cu+-mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.