High Drug Loading Capacity Research Articles

Hydrogel-based formulations for urothelial cancer therapy.

Drug infusion therapy after surgery for urothelial carcinoma is an effective measure to reduce cancer recurrence rate. Hydrogels are drug carriers with good biocompatibility and high drug loading capacity, which can optimize the pharmacokinetics of drugs in the urinary system to improve the therapeutic effect. Compared with the traditional free drug in situ perfusion, the hydrogel drug loading system can still maintain effective drug concentration in the face of continuous urinary flushing due to its good mucosal adhesion effect. The significantly prolonged drug retention time can not only improve the therapeutic effect of drugs, but also reduce the discomfort and risk of urinary tract infections caused by frequent drug infusion, and improve patient compliance. In addition, the combination of hydrogel with nanoparticles and magnetic materials can also improve the mucosal permeability and targeting effect of the hydrogel drug loading system, so as to overcome the mucus layer of urinary epithelium and the physiological barrier of tumor and minimize the impact on normal tissue and cell functions. At present, the research of hydrogels for urothelial cancer treatment involves chemotherapy, immunotherapy, gene therapy, inhibition of metabolism and multi strategy synergistic therapy. This review summarizes the research progress of hydrogels for the treatment of urothelial carcinoma, hoping to provide a reference for the future research of safe, reliable, effective, and advanced hydrogels with little side effects.

Chrysin Embedded Metal Organic Framework for Anticancer Drug Delivery.

Metal-organic frameworks (MOFs) have garnered significant attention in the field of cancer drug delivery owing to their porosity, high drug-loading capacity, and large surface area. In our recent research, we synthesized a redox-responsive MOF using zirconium (Zr) as the metal ion and 4,4-dithiobisbenzoic acid (DTBA) as the organic linker. The synthesis method employed was the hydrothermal method, and it was observed that the MOF synthesized at 400°C had a particle size of less than 200 nm and a zeta potential of +35 mV, indicating its suitability as a carrier for drug delivery. Chrysin, a natural anticancer drug, was used in this study. Glutathione, which is abundantly present in tumor cells, cleaves the disulfide bond in the organic ligand (DTBA), leading to faster drug release. By incorporating chrysin into the synthesized MOF, we observed faster in vitro drug release, with 88 and 89% at pH 7.4 and 5.5, respectively. The synthesis of ZrDTBA MOF opens up new opportunities for its application in drug delivery.

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-basedchemotherapy plus Gossypol with pro-apoptotic effects displays asynergisticeffect forkillingtumorcells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. Inthe patient-derived tumor xenograft (PDX)model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells.

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64nm) and a more negative zeta potential (-36.94 ± 0.32mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.

Simplified Gambogic Acid Prodrug Nanoparticles to Improve Efficiency and Reduce Toxicity for Clinical Translation Potential.

Poor in vivo characteristics of gambogic acid (GA) and difficulties in industrial manufacturing of its nanocarriers have hindered its clinical translation. Therefore, a reproducible nano-drug delivery system must be developed to realize simpler manufacture and address inherent defects of GA, such as short circulation and severe side effects, in order to facilitate its clinical application. Herein, a drug self-assembled nanoparticles (NPs) consisting of a hydrophobic prodrug based on GA and oleyl alcohol (OA), as well as vitamin E-polyethylene glycol succinate (TPGS) as a shield to improve the stability of the NPs is reported. The preparation method is simple enough to stably facilitate large-scale manufacturing. The self-assembled NPs exhibit a remarkably high drug-loading capacity, and their prolonged circulation enables the NPs to demonstrate superior antitumor efficacy in both cellular and animal models. The flexible hydrophobic long chain wraps GA groups, which mitigates vascular irritation and reduces hemolysis rates. Consequently, the prodrug nano-system addresses GA-related concerns regarding stability, efficacy, and safety, offering a simple, stable, and secure nano-platform for similar candidate drugs.

A Spironolactone-Based Prototype of an Innovative Biomedical Patch for Wound Dressing Applications.

The electrospinning process is an effective technique for creating micro- and nanofibers from synthetic and natural polymers, with significant potential for biomedical applications and drug delivery systems due to their high drug-loading capacity, large surface area, and tunable release times. Poly(L-lactic acid) (PLLA) stands out for its excellent thermo-mechanical properties, biodegradability, and bioabsorbability. Electrospun PLLA nanofibrous structures have been extensively investigated as wound dressings, sutures, drug delivery carriers, and tissue engineering scaffolds. This study aims to create and characterize electrospun PLLA membranes loaded with spironolactone (SP), mimicking active compounds of Ganoderma lucidum (GL), to develop a biodegradable patch for topical wound-healing applications. GL, a medicinal mushroom, enhances dermal wound healing with its bioactive compounds, such as polysaccharides and ganoderic acids. Focusing on GL extracts-obtained through green extraction methods-and innovative drug delivery, we created new fibers for wound-healing potential applications. To integrate complex mixtures of bioactive compounds into the fibers, we developed a prototype using a single pure substance representing the extract mixture. This painstaking work presents the results of the fabricating, wetting, moisture properties, material resilience, and full characterization of the product, providing a robust rationale for the fabrication of fibers imbued with more complex extracts.

Glycyrrhizic acid and glycyrrhetinic acid loaded cyclodextrin MOFs with enhanced antibacterial and anti-inflammatory effects for accelerating diabetic wound healing

A water stable cyclodextrin MOF (Cu-SD) was synthesized with γ-cyclodextrin derivative as organic ligand and Cu2+ as metal center to co-crystallizely load glycyrrhizic acid (GL) and glycyrrhetinic acid (GA). Cu-SD has a high drug loading capacity for GL (499.91 μg/mg) and GA (112.37 μg/mg), and the drug-loaded materials had a controlled release in different meadiums. In addition, Cu-SD and its drug loaded materials demonstrated better inhibiting α-glucosidase activity than the control drug acarbose. Furthermore, Cu-SD presented excellent antibacterial activity, and the antibacterial activity was significantly enhanced after GA and GL being encapsulated by Cu-SD. Moreover, both free and drug-loaded materials had good anti-inflammatory activities, and the anti-inflammatory effects of GL@Cu-SD and GA@Cu-SD were superior to those of their corresponding free drugs. Cu-SD, GL@Cu-SD and GA@Cu-SD demonstrated good biocompatibility and were applied to treat the wounds of diabetic rats. The experimental results showed that GL@Cu-SD and GA@Cu-SD had good promoting effects on the recovery of chronic diabetic wounds by suppressing wound inflammation.

Hybrid Liposome-MSN System with Co-Delivering Potential Effective Against Multidrug-Resistant Tumor Targets in Mice Model.

RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer. The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects. The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance. In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

Advancements in Micellar Formulation: Drug Delivery Vehicle for Water-Insoluble Drugs

: Micellar systems, particularly polymeric micelles, have emerged as a promising drug delivery vehicle for water-insoluble compounds. Polymeric micelles, self-assembled nanostructures made from amphiphilic block copolymers, have emerged as a promising drug delivery vehicle for water-insoluble compounds. These micelles offer high drug loading capacity, stability, and the ability to solubilize large amounts of hydrophobic drugs, making them an attractive option for delivering drugs with limited solubility and bioavailability. Their small size allows for efficient delivery and targeting of specific tissues or cells, reducing off-target effects and improving therapeutic outcomes. This review provides a brief overview of drug delivery system challenges, solutions, techniques of micelle formation, factors affecting micelle stability and drug loading, applications, pharmacokinetics and pharmacodynamics of micellar formulations, toxicological considerations, limitations, recent advancements, and clinical trials of micelles in drug delivery. By addressing these key aspects, this review seeks to provide a comprehensive understanding of the current status and prospects of polymeric micelles as a promising drug delivery system.

Poly (β-amino esters)/Mobil Composition of Matter 41-mediated delivery of siIL-1β alleviates deep vein thrombosis in rat hind limbs.

Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1β, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1β to silence IL-1β may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1β and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1β, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1β (PM@siIL-1β) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1β were evaluated. A rat hind limb DVT model was established, and PM@siIL-1β was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1β, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1β and t-PA were highly expressed in DVT patients, and IL-1β treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1β exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1β and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1β resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1β, VWF, and t-PA levels. Furthermore, PM@siIL-1β treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1β can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1β achieved efficient delivery and gene silencing of siIL-1β, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.

Enzyme-Responsive Micelles with High Drug-Loading Capacity for Antitumor Therapy.

To overcome the poor targeting of conventional chemotherapeutic drugs and the defects of low drug-loading capacity of conventional drug delivery systems, novel drug delivery systems with high drug-loading capacity are developed. Herein, the high drug-loaded mPEG79-GFLGDDD-DOX copolymer is first synthesized via an amide reaction, which can bond multiplex DOX. After PEGylation, the drug can resist the adsorption of proteins in the plasma in blood circulation, avoid being rapidly cleared out of the body, and prolong the circulation time of the drug in the blood, which is conducive to the enrichment of micelles in tumor tissues through the EPR effect. In tumor tissues, the peptide Glycine- Phenylalanine- Leucine- Glycine (GFLG) is recognized and sheared by overexpressed cathepsin B, which stripped the outer layer of methoxy polyethylene glycol (mPEG) and made it more readily available for uptake by tumor cells. After entering the tumor cells, the bonded DOX and the physically encapsulated DOX in the micelles played a synergistic role, realizing the killing of tumor cells, thus effectively enhancing the therapeutic effect on tumors. The findings in this work suggest that a high drug-loading drug delivery system has great potential in the clinical treatment of tumors.

Advancements in Hydrogel-Based Therapies for Ovarian Cancer: A Review.

Ovarian cancer, the most deadly gynecologic malignancy, is often resistant to conventional antitumor therapy due to various factors such as severe side effects, unexpected recurrence, and significant tissue damage. The limitations of current treatments and the resistance of invasive tumor cells contribute to these challenges. Hydrogel therapy has recently emerged as a potential treatment option for ovarian cancer, offering advantages such as controllability, biocompatibility, high drug loading capacity, prolonged drug release, and responsiveness to specific stimuli. Hence, the utilization of biodegradable hydrogels as carriers for chemotherapeutic agents has emerged as a significant concern in the field. Injectable hydrogel-based drug delivery systems, in particular, have demonstrated superior efficacy compared to traditional systemic chemotherapy for cancer treatment. The pliability of hydrogel therapy allows for access to anatomical regions that may be challenging for surgical intervention. This review article examines recent advancements in the application of hydrogels for diagnosing and treating ovarian cancer, while also proposing a novel direction for the use of hydrogel technology in this context. The objective of this article is to offer a novel point of reference and serve as a source of inspiration for the advancement of more precise and individualized cancer therapies.

Advancements of prodrug technologies for enhanced drug selectivity in pharmacotherapies.

The therapeutic effects of many pharmacotherapies have been explored, but disadvantages such as low drug specificity, drug resistance and side effects makes their effective delivery to target sites a great challenge. Consequently, a distinctive prodrug-based technology have emerged as an effective treatments because of their distinctive advantages, such as high drug loading capacity, precise targeting, reduced side effects and spatial and temporal controllability. In particular, the use of gamma/X-ray-mediated strategies in radiotherapy is a new strategy that could enable the precise drug release from implanted devices. This review presents readers with the current state of prodrug therapy and reports the design protocols of rational and effective prodrugs for clinical use.

Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier

Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy, and pursue high drug-load NPs with surface designs. Compared to solid and mesoporous NPs, we found the spiky tubular NPs reserved the NPs' antifouling properties (or shedding of “protein corona”), promoted better endothelial penetration and less destruction in vitro and in vivo. Such effects could be attributed to their spiky surface structures, which can limit the NP-protein interaction area and promote the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy and lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of vascular endothelia. As a result, the spiky tubular NPs demonstrated its advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Exploiting such spiky tubular surface modification, we can improve the NP delivery efficiency and prohibit the leakiness of vascular endothelia, helping address challenges faced by tumor migration in nanomedicine applications for cancer therapy.

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models. Benchtop characterization verified the optimized oleogel-based bupivacaine formulation design, demonstrating a homogenous stable oleogel with sufficient injectability due to shear-thinning properties, high drug loading capacity and first-order drug release kinetics over 5days. In vivo assessment in two pig post-operative pain models demonstrated that the oleogel-based bupivacaine formulation can provide statistically significant multi-day analgesia in two routes of administration: local instillation directly into a surgical site and ultrasound-guided peripheral nerve block injection. Pharmacokinetic assessment of ALX005 found that Cmax values were not statistically different from the bupivacaine HCl control, with no clinical signs of local anesthetic systemic toxicity observed, when administering up to 2.7 and 8.1 times the control dose of bupivacaine HCl. This study demonstrates the pre-clinical safety and efficacy of an injectable oleogel-based bupivacaine formulation and explores its utility as a single-administration long-acting local anesthetic product for post-operative pain management that can be used in both local and regional anesthetic applications.

Drug Loading in Chitosan-Based Nanoparticles.

Chitosan nanoparticles (CSNPs) are promising vehicles for targeted and controlled drug release. Recognized for their biodegradability, biocompatibility, low toxicity, and ease of production, CSNPs represent an effective approach to drug delivery. Encapsulating drugs within nanoparticles (NPs) provides numerous benefits compared to free drugs, such as increased bioavailability, minimized toxic side effects, improved delivery, and the incorporation of additional features like controlled release, imaging agents, targeted delivery, and combination therapies with multiple drugs. Keys parameters in nanomedicines are drug loading content and drug loading efficiency. Most current NP systems struggle with low drug loading, presenting a significant challenge to the field. This review summarizes recent research on developing CSNPs with high drug loading capacity, focusing on various synthesis strategies. It examines CSNP systems using different materials and drugs, providing details on their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stability, and applications in drug delivery. Additionally, the review discusses factors affecting drug loading, providing valuable guidelines for future CSNPs' development.

Biocompatibility and potential anticancer activity of gadolinium oxide (Gd2O3) nanoparticles against nasal squamous cell carcinoma

Chemotherapy as a cornerstone of cancer treatment is slowly being edged aside owing to its severe side effects and systemic toxicity. In this case, nanomedicine has emerged as an effective tool to address these drawbacks. Herein, a biocompatible carrier based on bovine serum albumin (BSA) coated gadolinium oxide nanoparticles (Gd2O3@BSA) was fabricated for curcumin (CUR) delivery and its physicochemical features along with its potential anticancer activity against nasal squamous cell carcinoma were also investigated. It was found that the fabricated Gd2O3@BSA containing CUR (Gd2O3@BSA-CUR) had spherical morphology with hydrodynamic size of nearly 26 nm, zeta-potential of -36 mV and high drug (CUR) loading capacity. Drug release profile disclosed that the release of CUR from the prepared Gd2O3@BSA-CUR nanoparticles occurred in a sustained- and pH-dependent manner. Also, in vitro cytotoxicity analysis revealed that the fabricated Gd2O3@BSA nanoparticles possessed excellent biosafety toward HFF2 normal cells, while Gd2O3@BSA-CUR appeared to display the greatest anticancer potential against RPMI 2650 and CNE-1 cancer cell lines. The results also show that the Gd2O3@BSA nanoparticles were compatible with the blood cells with minor hemolytic effect (< 3%). The manufactured NPs were found to be completely safe for biological applications in an in vivo subacute toxicity study. Taken together, these finding substantiate the potential anticancer activity of Gd2O3@BSA-CUR nanoparticles against nasal squamous cell carcinoma, but the results obtained demand further studies to assess their full potential.

Nanogel: A versatile drug delivery system for the treatment of various diseases and their future perspective.

Nanogel (NG) drug delivery systems have emerged as promising tools for targeted and controlled drug release, revolutionizing treatment approaches across various diseases.Their unique physicochemical properties, such as nano size, high surface area,biocompatibility, stability, and tunable drug release, make themideal carriers for a wide range of therapeutic agents. Nanogels (NGs), characterized by their 3D network of crosslinked polymers, offer unique edges like high drug loading capacity, controlled release, and targeted delivery. Additionally, the diverse applications of NGs in medical therapeutics highlight their versatility and potential impact on improving patient outcomes. Their application spans cancer treatment, infectious diseases, and chronic conditions, allowing for precise drug delivery to specific tissues or cells, minimizing side effects, and enhancing therapeutic efficacy. Despite their potential, challenges such as scalability, manufacturing reproducibility, and regulatory hurdles must be addressed. Achieving clinical translation requires overcoming these obstacles to ensure therapeutic payloads' safe and efficient delivery. Strategies such as surface modification and incorporating stimuli-responsive elements enhanced NG performance and addressed specific therapeutic challenges. Advances in nanotechnology, biomaterials, and targeted drug design offer opportunities to improve the performance of NGs and address current limitations. Tailoring NGs for exploring combination therapies and integrating diagnostics for real-time monitoring represent promising avenues for future research. In conclusion, NG drug delivery systems have demonstrated tremendous potential in diverse disease applications. Overcoming challenges and leveraging emerging technologies will pave the way for their widespread clinical implementation, ushering in a new era of precision medicine and improved patient care.

Manganese-coordinated nanoparticle with high drug-loading capacity and synergistic photo-/immuno-therapy for cancer treatments

Stimulator of interferon genes (STING) agonists have shown promise in cancer treatment by stimulating the innate immune response, yet their clinical potential has been limited by inefficient cytosolic entry and unsatisfactory pharmacological activities. Moreover, aggressive tumors with “cold” and immunosuppressive microenvironments may not be effectively suppressed solely through innate immunotherapy. Herein, we propose a multifaceted immunostimulating nanoparticle (Mn-MC NP), which integrates manganese II (Mn2+) coordinated photosensitizers (chlorin e6, Ce6) and STING agonists (MSA-2) within a PEGylated nanostructure. In Mn-MC NPs, Ce6 exerts potent phototherapeutic effects, facilitating tumor ablation and inducing immunogenic cell death to elicit robust adaptive antitumor immunity. MSA-2 activates the STING pathway powered by Mn2+, thereby promoting innate antitumor immunity. The Mn-MC NPs feature a high drug-loading capacity (63.42 %) and directly ablate tumor tissue while synergistically boosting both adaptive and innate immune responses. In subsutaneous tumor mouse models, the Mn-MC NPs exhibit remarkable efficacy in not only eradicating primary tumors but also impeding the progression of distal and metastatic tumors through synergistic immunotherapy. Additionally, they contribute to preventing tumor recurrence by fostering long-term immunological memory. Our multifaceted immunostimulating nanoparticle holds significant potential for overcoming limitations associated with insufficient antitumor immunity and ineffective cancer treatment.

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis

HighlightsSite-selective superassembly was used to synthesize a nanorobot with bionic rod-shaped head/hollow tail structure, exhibiting strong photothermal effect, high drug loading capacity, precise and controlled drug release, and excellent motility.Injectable regenerated silk fibroin (RSF) nanofibril hydrogels were developed via simple sonication, offering significant production, structural, and performance advantages.Nanorobot/thrombin (Thr)/RSF nanofibril hydrogels reduced intraoperative bleeding of hepatocellular carcinoma (HCC) spinal metastasis, provided starvation embolization, and prevented post-surgery recurrence.Nanorobot/Thr/RSF nanofibril hydrogels inhibited blood supply to residual tumors and reduced neovascularization, inhibiting post-surgery HCC spinal metastasis recurrence.