Multifunctional Nanoplatform Research Articles

Black Phosphorus Quantum Dot Loaded Bioinspired Nanoplatform Synergized with aPD-L1 for Multimode Cancer Immunotherapy.

Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), and immunomodulator PolyMetformin (PM) in hybrid membrane-camouflaged liposomes. Specifically, the hybrid cell membrane coating derived from the fusion of cancer cell membrane and red blood cell membrane displays excellent tumor targeting efficiency and long blood circulation property due to the innate features of both membranes. After collaboration with aPD-L1-based immune checkpoint blockade therapy, a boosted immunotherapeutic effect is obtained due to elevated dendritic cell maturation and T cell activation. Significantly, laser-irradiated BPP@RTL combined with aPD-L1 effectively eliminates primary tumors and inhibits lung metastasis in 4T1 breast tumor model, offering a promising treatment plan to develop personalized antitumor strategy.

Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2+ BC) due to the challenges in addressing blood circulation and tumor accumulation. Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2+ BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a “nano-thermal-bomb”. Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor. Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2+ BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2+ cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions. Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy. In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Photothermal/photodynamic synergistic antibacterial study of MOF nanoplatform with SnFe2O4 as the core

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.

Graphene acid quantum dots: A highly active multifunctional carbon nano material that intervene in the trajectory towards neurodegeneration

Carbon dots (CDs) are carbon nano materials (CNMs) that find use across several biological applications because of their water solubility, biocompatible nature, eco-friendliness, and ease of synthesis. Additionally, their physiochemical properties can be chemically tuned for further optimization towards specific applications. Here, we investigate the efficacy of C70-derived Graphene Acid Quantum Dots (GAQDs) in mitigating the transformation of soluble, monomeric Hen Egg-White Lysozyme (HEWL) to mature fibrils during its amyloidogenic trajectory. Our findings reveal that GAQDs exhibit dose-dependent inhibition of HEWL fibril formation (up to 70 % at 5 mg/mL) without affecting mitochondrial membrane potential or inducing apoptosis at the same density. Furthermore, GAQDs scavenged reactive oxygen species (ROS); achieving a 50 % reduction in ROS levels at a mere 100 µg/mL when exposed to a standard free radical generator. GAQDs were not only found to be biocompatible with a human neuroblastoma-derived SHSY-5Y cell line but also rescued the cells from rotenone-induced apoptosis. The GAQD-tolerance of SHSY-5Y cells coupled with their ability to restitute cells from rotenone-dependent apoptosis, when taken in conjunction with the biocompatibility data, indicate that GAQDs possess neuroprotective potential. The data position this class of CNMs as promising candidates for resolving aberrant cellular outputs that associate with the advent and progress of multifactorial neurodegenerative disorders including Parkinson’s (PD) and Alzheimer’s diseases (AD) wherein environmental causes are implicated (95 % etiology). The data suggest that GAQDs are a multifunctional carbon-based sustainable nano-platform at the intersection of nanotechnology and neuroprotection for advancing green chemistry-derived, sustainable healthcare solutions.

Hybrid Cell Membrane-Based Nanoplatforms for Enhanced Immunotherapy against Cancer and Infectious Diseases.

Immunotherapy based on nanoplatforms is a promising approach to treat cancer and infectious diseases, and it has achieved considerable progress in clinical practices. Cell membrane-based nanoplatforms endow nanoparticles with versatile characteristics, such as half-life extension, targeting ability, and immune-system regulation. However, monotypic cell membrane usually fails to provoke strong immune response for immunotherapy while maintaining good biosafety. The integration of different cell-membrane types provides a promising approach to construct multifunctional nanoplatforms for improved immunotherapeutic efficacy by enhancing immunogenicity or targeting function, evading immune clearance, or combining with other therapeutic modalities. In this review, the design principles, preparation strategies, and applications of hybrid cell membrane-based nanoplatforms for cancer and infection immunotherapy are first discussed. Furthermore, the challenges and prospects for the potential clinical translation of hybrid cell membrane-based nanoplatforms are discussed.

Development of a multifunctional nano-hydroxyapatite platform (nHEA) for advanced treatment of severely infected full-thickness skin wounds

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. Statement of significanceTreating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo, making it a promising treatment for severely infected skin injuries.

Multifunctional Hierarchical Nanoplatform with Anisotropic Bimodal Mesopores for Effective Neural Circuit Reconstruction after Spinal Cord Injury.

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2-PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.

Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

Exploration of the photothermal role of curcumin-loaded targeted carbon nanotubes as a potential therapy for melanoma cancer

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT–PCA–FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV–visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT–PCA–FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT–PCA–FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT–FA–PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT–PCA–FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.

The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.

Magnetic graphene oxide functionalized alginate-g-poly(2-hydroxypropylmethacrylamide) nanoplatform for near-infrared light/pH/magnetic field-sensitive drug release and chemo/phototherapy

Multifunctional nanoplatforms developed from natural polymers and graphene oxide (GO) with enhanced biological/physicochemical features have recently attracted attention in the biomedical field. Herein, a new multifunctional near-infrared (NIR) light-, pH- and magnetic field-sensitive hybrid nanoplatform (mGO@AL-g-PHPM@ICG/EP) is developed by combining iron oxide decorated graphene oxide nanosheets (mGO) and poly(2-hydroxypropylmethacrylamide) grafted alginate (AL-g-PHPM) copolymer loaded with indocyanine green (ICG) and etoposide (EP) for chemo/phototherapy. The functional groups, specific crystal structure, size, morphology, and thermal stability of the nanoplatform were fully characterized by XRD, UV, FTIR, AFM/TEM/FE-SEM, VSM, DSC/TG, and BET analyses. In this platform, the mGO and ICG, as phototherapeutic agents, demonstrate excellent thermal effects and singlet oxygen production under NIR-light (808 nm) irradiation. The XRD and DSC analysis confirmed the amorphous state of the ICG/EP in the nanoparticles. In vitro photothermal tests proved that the mGO@AL-g-PHPM@ICG/EP nanoparticles had outstanding light stability and photothermal conversion ability. The in vitro release profiles presented NIR light-, pH- and magnetic field-controlled EP/ICG release behaviors. In vitro experiments demonstrated the excellent antitumor activity of the mGO@AL-g-PHPM@ICG/EP against H1299 tumor cells under NIR laser. Benefiting from its low-cost, facile preparation, and good dual-modal therapy, the mGO@AL-g-PHPM@ICG/EP nanoplatform holds great promise in multi-stimuli-sensitive drug delivery and chemo/phototherapy.

PLGA-based nanocarriers for combined delivery of colchicine and purpurin 18 in cancer therapy: Multimodal approach employing cancer cell spheroids

Improving the anticancer efficacy of chemotherapeutic drugs and photosensitizers requires innovative multifunctional nanoplatforms. This study introduces a chemo- and phototherapeutic drug delivery system (DDS) based on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), both PEGylated and non-PEGylated, with a mean size of 200 ± 75 nm. Colchicine (Colch) and purpurin18 (P18) were co-encapsulated into these NPs, and their in vitro drug release profiles were investigated. The anticancer potential of these systems was evaluated across various cell lines (i.e., CaCo-2, PC-3, MCF-7, and MRC-5 cells), demonstrating enhanced NP uptake by cancer cells compared to free drugs. Co-administration of Colch and P18 in 2D and 3D cell line models exhibited a synergistic effect, harnessing both chemotherapeutic and photodynamic effects, leading to higher cancer cell elimination efficacy. This newly developed multifunctional DDS presents a promising platform for combined chemo- and photodynamic therapy in cancer treatment.

Multimodal Tetrahedral DNA Nanoplatform for Surprisingly Rapid and Significant Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a life-threatening disease associated with the rapid development of inflammatory storms, level elevation of reactive oxygen species (ROS), and hepatocyte necrosis, which results in high short-term mortality. Except for liver transplantation, no effective strategies are available for ALF therapy due to the rapid disease progression and narrow window of therapeutic time. Therefore, there is an urgent demand to explore the fast and effective modalities for ALF treatment. Herein, a multifunctional tetrahedral DNA nanoplatform (TDN) is constructed by incorporating tumor necrosis factor-α siRNA (siTNF-α) through DNA hybridization and antioxidant manganese porphyrin (MnP4) via π-π stacking interaction with G-quadruplex (G4) for surprisingly rapid and significant ALF therapy. TDN-siTNF-α/-G4-MnP4 silences TNF-α of macrophages by siTNF-α and polarizes them to the anti-inflammatory M2 phenotype, providing appropriate microenvironments for hepatocyte viability. Additionally, TDN-siTNF-α/-G4-MnP4 scavenges intracellular ROS by MnP4, protecting hepatocytes from oxidative-stress-associated cell death. Furthermore, TDN itself promotes hepatocyte proliferation by modulating the cell cycle. TDN-siTNF-α/-G4-MnP4 shows almost complete liver accumulation after intravenous injection and exhibits excellent therapeutic efficacy of ALF within 2h. The multifunctional DNA nanoformulation provides an effective strategy for rapid ALF therapy, expanding its application for innovative treatments of liver diseases.

A multifunctional nanoplatform with “disruption and killing” function to improve the efficiency of conventional antibiotics for biofilm eradication

Due to the absence of timely and effective therapies, infections induced by bacterial biofilms have been widely acknowledged as a significant global public health concern. In modern times, aside from surgical intervention (when appropriate), antibiotics are the sole clinical option for treating biofilm-associated infections. However, the rise of drug resistance, as well as the poor therapeutic effects of current treatment regimens in eliminating biofilms highlight the requirement for novel strategies to enhance the accessibility of antibiotics in the “post-antibiotic era”. The current study presents a multifunctional nanoplatform equipped with a “disruption and killing” function to enhance the effectiveness of conventional antibiotics for the eradication of biofilms. Herein, mesoporous silica nanoparticles were employed as carriers to encapsulate the model antibiotic rifampicin (Rif). Subsequently, the nanoparticles were coated with layers of the tannic acid/iron ion (TA/Fe) complex and immobilized with α-amylase. The α-amylase present in the outer layer can degrade the polysaccharides of extracellular polymeric substances (EPS), which in turn disrupts the structural integrity of the biofilms, thus facilitating the entry of the nanoplatform. When exposed to near-infrared (NIR) light, the TA/Fe complex layers can generate heat, which facilitates the release of Rif and increases the bacterial uptake of Rif by damaging the bacterial cell membrane, ultimately resulting in the elimination of bacteria within biofilms. The in vitro experiments demonstrated that this nanoplatform effectively eliminated over 99% of biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa when exposed to NIR radiation for 10 min. Additionally, in vivo experimental findings further validated the extensive therapeutic efficacy of this nanoplatform against biofilm-infected wounds, accelerating the rate of healing and reducing inflammatory reactions. To summarize, this nanoplatform provides a novel avenue to improve the effectiveness of conventional antibiotics in eradicating bacterial biofilms.

Multifunctional Ac@ZIF-8/AgNPs nanoplatform with pH-responsive and ROS scavenging antibacterial properties promotes infected wound healing

The development of non-antibiotic strategies for combating bacterial infections, particularly through reactive oxygen species (ROS) accumulation accompanying inflammation, has attracted much attention. Despite Allicin (Ac) emerges as a promising antimicrobial agent with wide and remarkable bioactivity, it still displays quite limited ROS scavenging and anti-inflammation capacity due to uncontrolled and poor bioavailability. Herein, a multifunctional nanoplatform with pH-dependent and ROS-scavenging antibacterial, anti-inflammatory and proangiogenic properties is introduced to promote infected wound healing by integrating Ac into silver nanoparticles (AgNPs)-loaded zeolite imidazole framework (ZIF-8), namely Ac@ZIF-8/AgNPs. Primarily, the nanoplatform is activated and controlled release in the infection microenvironment, with disrupting biofilms, scavenging ROS and antibacterial capacitys, outperforming conventional Ac. Moreover, in the mouse models induced by bacterial infection, Ac@ZIF-8/AgNPs can alleviate the inflammatory condition, scavenge ROS, facilitate the regeneration of collagen fiber and enhance vascular formation, collectively accelerating wound healing. Overall, this biocompatible nanoplatform is provided as a reliable approach to solve the long-standing problem of infected wound healing.

Multifunctional iron oxide‐hydroxide based nanorods for hydrogen sulfide scavenging assisted synergistic photothermal-chemotherapy of colon cancer

The tumor microenvironment responsive multifunctional nanoplatforms with integrated diagnosis and therapy have recently received great attention in anti-cancer treatment. In this study, we developed biocompatible iron oxide-hydroxide-based nanorods (DOX-FPT NRs) for MR imaging and H2S scavenging assisted synergistic photothermal-chemotherapy of colon cancer, which is fabricated by modifying polydopamine (PDA) and transferrin (Tf) on the surface of iron oxide hydroxide (FeOOH) nanorods. The prepared DOX-FPT NRs could precisely target the colon cancer cells through transferrin ligand-receptor-mediated targeting and effectively scavenge endogenous H2S to prohibit the growth of colon cancer. Meanwhile, the considerable drug loading capability and outstanding photothermal conversion efficiency are permitted by the PDA shell modification. In addition, the H2S scavenging assisted photothermal-chemotherapy showed an excellent therapeutic effect on CT26 cells via in vitro cell test. Therefore, the prepared DOX-PFT NRs will be a promising nanoplatform to enhance the therapeutic effect of colon cancer through the treatment strategy of H2S scavenging-assisted synergistic photothermal chemotherapy.

Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.

Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.