Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications.

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.

Sonodynamic and sonomechanical effect on cellular stemness and extracellular physicochemical environment to potentiate chemotherapy.

BACKGROUND: Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix (ECM) of tumor, as well as the potential resistance to chemotherapy, have severely impeded the resulting overall efficacy of HAP. RESULTS: A HAP potentiating strategy is proposed based on ultrasound responsive nanodroplets (PTP@PLGA), which is composed of protoporphyrin (PpIX), perfluoropropane (PFP) and a typical HAP, tirapazamine (TPZ). The intense vaporization of PFP upon ultrasound irradiation can magnify the sonomechanical effect, which loosens the ECM to promote the penetration of TPZ into the deep hypoxic region. Meanwhile, the PpIX enabled sonodynamic effect can further reduce the oxygen level, thus activating the TPZ in the relatively normoxic region as well. Surprisingly, abovementioned ultrasound effect also results in the downregulation of the stemness of cancer cells, which is highly associated with drug-refractoriness. CONCLUSIONS: This work manifests an ideal example of ultrasound-based nanotechnology for potentiating HAP and also reveals the potential acoustic effect of intervening cancer stem-like cells.

A "Ferroptosis-Amplifier" Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy.

The unique "Iron Addiction" feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel "Ferroptosis Amplification" strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This "Ferroptosis Amplifier" hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this "Ferroptosis Amplification" strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.

Comparative optimization of polysaccharide-based nanoformulations for cardiac RNAi therapy.

Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.

A universal strategy for constructing high-performance silica-based AIE materials for biomedical application.

As an emerging fluorophore, aggregation-induced emission luminogens (AIEgens) have received widespread attention in recent years, but the inherent drawbacks of AIEgens, such as the poor water-solubility and insufficient fluorescence stability in complex environments, restrict their performance in practical applications. Herein, we report a universal strategy based on hydrophobic dendritic mesoporous silica (HMSN) that can integrate different AIE molecules to construct multi-color fluorescent AIE materials. Specifically, HMSN with central radial pores was used as a powerful carrier for direct loading AIE molecules and restricting their intramolecular motions. Due to the pore-domain restriction effect and hydrophobic interaction, the obtained silica-based AIE materials have bright fluorescence with a maximum quantum yield of 68.38%, high colloidal/fluorescence stability, and excellent biosafety. Further, these silica-based AIE materials can be conjugated with functional antibodies to obtain probes with different targetability. After integration with immunomagnetic beads, the prepared detection probes achieved the quantitative detection of cardiac troponin I with the limit of detection (LOD) of 0.508 ng/mL. Overall, the targeting probes stemming from silica-based AIE materials can not only achieve cell-specific imaging, but quantify the number of Jurkat cells (LOD = 270 cells/mL) to further determine the specific etiology of the disease.

Enzyme-like biomimetic oral-agent enabling modulating gut microbiota and restoring redox homeostasis to treat inflammatory bowel disease.

Reactive oxygen species (ROS), immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease (IBD). Herein, a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed, using yeast cell wall (YCW) as the outer shell and zinc-doped Prussian blue analogue (ZnPBA) nanozyme inside. When orally administered, the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E. coli, meanwhile exhibiting improved intestinal epithelial barrier repair. Moreover, it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway. More importantly, the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity, significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E. coli to the same level as normal mice. Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

Ca & Mn dual-ion hybrid nanostimulator boosting anti-tumor immunity via ferroptosis and innate immunity awakening.

Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment (TME), triple-negative breast cancer (TNBC) has been poorly responsive to immunotherapy so far. Herein, a Ca & Mn dual-ion hybrid nanostimulator (CMS) is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening, which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently. On one hand, glutathione (GSH) depletion and reactive oxygen species (ROS) generation can be achieved due to the mixed valence state of Mn in CMS. On the other hand, as an exotic Ca2+ supplier, CMS causes mitochondrial Ca2+ overload, which further amplifies the oxidative stress. Significantly, tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxidation (LPO). More impressively, CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway, which promotes polarization of tumor-associated macrophages (TAMs) and activation of dendritic cells (DCs) for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes (CTLs) into tumor tissues. Taken together, this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity, offering a new perspective for effective tumor immunotherapy of TNBC.

Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme.

The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology. Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression, metastasis, and poor outcome of cancer, while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization. Thus, the mutually-beneficial interplay between pathogens and tumors, named "pathogen-tumor symbionts", is probably a potential therapeutic site for tumor treatment. Herein, we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens, F. nucleatum, to break the symbiont and synergize to kill colorectal cancer (CRC) cells. This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme (BSA-Cu SAN) which was inspired by the structures of native enzymes that are based on protein, with metal elements as the active center. BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species (ROS) and depleting GSH. The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F. nucleatum in situ to destroy pathogen-tumor symbionts. As a result, ROS resistance of CRC through elevated autophagy mediated by F. nucleatum was relieved, contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN. Particularly, BSA-Cu SAN experiences renal clearance, avoiding long-term systemic toxicity. This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.

Recent Progress and Perspectives on Photocathode Materials for CO2 Catalytic Reduction.

The continuous consumption of fossil energy and excessive emissions of carbon dioxide (CO2) have caused a serious energy crisis and led to the greenhouse effect. Using natural resources to convert CO2 into fuel or high-value chemicals is considered to be an effective solution. Photoelectrochemical (PEC) catalysis utilizes abundant solar energy resources, combined with the advantages of photocatalysis (PC) and electrocatalysis (EC), to achieve efficient CO2 conversion. In this review, the basic principles and evaluation criteria, of PEC catalytic reduction to CO2 (PEC CO2RR), are introduced. Next, the recent research progress on typical kinds of photocathode materials for CO2 reduction are reviewed, and the structure-function relationships between material composition/structure and activity/selectivity are discussed. Finally, the possible catalytic mechanisms and the challenges of using PEC to reduce CO2 are proposed.

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury.

Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. Fusobacterium nucleatum, a core pathogen of colorectal cancer (CRC), is an important cause of low therapeutic efficacy and metastasis. Thus, the modulation of intratumoral pathogens may provide a target for cancer therapy and metastasis inhibition. Herein, we propose an intratumoral F. nucleatum-modulating strategy for enhancing the therapeutic efficacy of CRC and inhibiting lung metastasis by designing an antibacterial nanoplatform (Au@BSA-CuPpIX), which produced reactive oxygen species (ROS) under ultrasound and exhibited strong antibacterial activity. Importantly, Au@BSA-CuPpIX reduced the levels of apoptosis-inhibiting proteins by inhibiting intratumoral F. nucleatum, thereby enhancing ROS-induced apoptosis. In vivo results demonstrated that Au@BSA-CuPpIX effectively eliminated F. nucleatum to enhance the therapeutic efficacy of sonodynamic therapy (SDT) for orthotopic CRC and inhibit lung metastasis. Notably, entrapped gold nanoparticles reduced the phototoxicity of metalloporphyrin accumulated in the skin during tumor treatment, preventing severe inflammation and damage to the skin. Therefore, this study proposes a strategy for the elimination of F. nucleatum in CRC to enhance the therapeutic effect of SDT, thus providing a promising paradigm for improving cancer treatment with fewer toxic side effects and promoting the clinical translational potential of SDT.

Recent Progress in Advanced Hydrogel-Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization.

Transcatheter arterial embolization, a minimally invasive treatment to deliberately occlude the blood vessels, has become a safe and effective procedure for the management of vascular diseases and benign/malignant tumors. Particularly, hydrogel-based embolic agents have garnered much attention because of their potential to address some of the limitations of clinically used embolic agents and can be rationally designed to impart more favorable characteristics or functions. In this review, the recent progress toward the development of polymer-based hydrogels for effective endovascular embolization, including the in situ gelling hydrogels mediated by physically or chemically crosslinking, imageable hydrogels for intraprocedural and postprocedural feedback, use of hydrogels as the drug depot for local delivery of therapeutic drugs, hemostatic hydrogels inducing extrinsic or intrinsic coagulation of blood, stimuli-responsive shape memory hydrogels as the smart embolization devices, and hydrogels incorporating external-stimuli functional materials for multidisciplinary therapy, is systemically summarized. Moreover, the potential considerations of hydrogel-based embolic agents confronted in therapeutic embolization are pointed out. Finally, the perspectives for the development of more effective embolic hydrogels are also highlighted.

Cobalt protoporphyrin-induced nano-self-assembly for CT imaging, magnetic-guidance, and antioxidative protection of stem cells in pulmonary fibrosis treatment.

Mesenchymal stem cells (MSCs) transplantation is a promising approach for pulmonary fibrosis (PF), however it is impeded by several persistent challenges, including the lack of long-term tracking, low retention, and poor survival of MSCs, as well as the low labeling efficiency of nanoprobes. Herein, a cobalt protoporphyrin IX (CoPP) aggregation-induced strategy is applied to develop a multifunctional nano-self-assembly (ASCP) by combining gold nanoparticle (AuNPs), superparamagnetic iron oxide nanoparticles (SPIONs), and CoPP through a facile solvent evaporation-driven approach. Since no additional carrier materials are employed during the synthesis, high loading efficiency of active ingredients and excellent biocompatibility are achieved. Additionally, facile modification of the ASCPs with bicyclo[6.1.0]nonyne (BCN) groups (named as ASCP-BCN) enables them to effectively label MSCs through bioorthogonal chemistry. The obtained ASCP-BCN could not only help to track MSCs with AuNP-based computed tomography (CT) imaging, but also achieve an SPIONs-assisted magnetic field based improvement in the MSCs retention in lungs as well as promoted the survival of MSCs via the sustained release of CoPP. The in vivo results demonstrated that the labeled MSCs improved the lung functions and alleviated the fibrosis symptoms in a bleomycin-induced PF mouse model. Collectively, a novel ASCP-BCN multifunctional nanoagent was developed to bioorthogonally-label MSCs with a high efficiency, presenting a promising potential in the high-efficient MSC therapy for PF.

In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.

Though the development of the diverse hypoxia-activated prodrugs (HAPs) has made great progresses in the last several decades, current cancer therapy based on HAPs still suffers many obstacles, e.g., poor therapeutic outcome owing to hard deep reaching to hypoxic region, and the occurrence of metastasis due to hypoxia. Inspired by engineered niches, a novel functional chitosan polymer (CS-FTP) is synthesized for construction of a hydrogel-based bio-niche (CS-FTP-gel) in aiming at remodeling tumor hypoxic microenvironment. The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor, in which a HAP (i.e., AQ4N) could be physically encapsulated, resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy. Furthermore, Pazopanib (PAZ) conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation, eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model. This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.

An Endogenous H2S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer.

Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of •OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.

Construction of Heterostructured Sn/TiO2 /Si Photocathode for Efficient Photoelectrochemical CO2 Reduction.

Using renewable energy to convert CO2 into liquid products, as a sustainable way to produce fuels and chemicals, has attracted intense attention. Herein, a novel heterostructured photocathode composed of Si wafer, TiO2 layer, and Sn metal particles has been successfully fabricated by combining of a facile hydrothermal and electrodeposition method. The obtained Sn/TiO2 /Si photocathode shows enhanced light absorption performance by the surface plasmon resonance effect of Sn metal. Especially, the Sn/TiO2 /Si photocathode together with rich oxygen vacancy defects jointly promote photoelectrochemical CO2 reduction, harvesting a high faradaic efficiency of HCOOH and a desirable average current density (-4.72 mA cm-2 ) at -1.0 V vs. reversible hydrogen electrode. Significantly, the photocathode Sn/TiO2 /Si also shows good stability due to the design of protecting layer TiO2 . This study provides a facile strategy of constructing an efficient photocathode to improve the light absorption performance and the electron transfer efficiency, exhibiting great potential in the CO2 reduction.

Surface Stability and Morphology of Calcium Phosphate Tuned by pH Values and Lactic Acid Additives: Theoretical and Experimental Study.

The ubiquitous mineralization of calcium phosphate (CaP) facilitates biological organisms to produce hierarchically structured minerals. The coordination number and strength of Ca2+ ions with phosphate species, oxygen-containing additives, and solvent molecules played a crucial role in tuning nucleation processes and the surface stability of CaP under the simulated body fluid (SBF) or aqueous solutions upon the addition of oligomeric lactic acid (LACn, n = 1, 8) and changing pH values. As revealed by ab initio molecular dynamics (AIMD), density functional theory (DFT), and molecular dynamics (MD) simulations as well as high-throughput experimentation (HTE), the binding of LAC molecules with Ca2+ ions and phosphate species could stabilize both the pre-nucleation clusters and brushite (DCPD, CaHPO4·2H2O) surface through intermolecular electrostatic and hydrogen bonding interactions. When the concentration of Ca2+ ions ([Ca2+]) is very low, the amount of the formed precipitation decreased with the addition of LAC based on UV-vis spectroscopic analysis due to the reduced chance for the LAC capped Ca2+ ions to coordinate with phosphates and the increased solubility in the acid solution. With the increasing [Ca2+] concentration, the kinetically stable DCPD precipitation was obtained with high Ca2+ coordination number and low surface energy. Morphologies of DCPD precipitation are in plate, needle, or rod, depending on the initial pH values that were tuned by adding NH3·H2O, HCl, or CH3COOH. The prepared samples at pH ≈ 7.4 with different Ca/P ratios exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications.

Microfluidics-Assisted Engineering of pH/Enzyme Dual-Activatable ZIF@Polymer Nanosystem for Co-Delivery of Proteins and Chemotherapeutics with Enhanced Deep-Tumor Penetration.

The impermeable barriers of solid tumors restrict the co-delivery of protein-based drugs and chemotherapeutics for cancer treatment. Therefore, we developed a ZIF-DOX/RA@DG nanosystem that encapsulates ribonuclease A (RA) and doxorubicin (DOX) in a zeolitic imidazolate framework (ZIF-8) core, with a dextran-based coating (DG). The nanosystem exhibits dual-responsiveness due to γ-glutamyl transpeptidase-activatable cationization and acidic microenvironment-triggered degradation. The DG-coating process was achieved using a microfluidic approach, which stabilized the polymer responsiveness, ZIF-8-based structure, and bioactivity of the encapsulated therapeutics. In vivo results confirmed that the nanosystem could co-deliver RA and DOX to deep impermeable lesions with a synergistic anticancer therapeutic effects. Such a multi-drug delivery system based on an intelligent-responsive design and a microfluidics-assisted synthesis strategy shows great clinical prospects.

Thermosensitive and tum or microenvironment activated nanotheranostics for the chemodynamic/photothermal therapy of colorectal tumor.

This research proposes the one-pot preparation of polydopamine (PDA) decorated mesoporoussilica nanoparticle (PMSN) for the thermal and tumor micro-environment (TME) responsive colorectal tumor therapy. The pores of PMSN were used for the Fe3+ loading. Lauric acid (LA), a phase-change ligand, was selected as a "doorkeeper" to coat the surface of Fe3+-loaded PMSN and prevent the undesired leakage of Fe3+. Bovine serum albumin (BSA) was selected as a stabilizer to endow the PMSN-Fe-LA-BSA nanopartilces (PMFLB) with colloidal stability. Under the near infrared laser, the light-sensitive PDA produced significant heat to kill the colorectal cancer cells via hyperthermia. Moreover, the heat induced the phase-change of LA and triggered the release of Fe3+, which further reacted with the endogenous H2S in the colorectal TME. After that, the Fe3+ was transformed into Fe2+, which triggered the Fenton reaction with the H2O2 in the TME and effectively generated hydroxyl radical (·OH). Finally, the Fe2+ was transformed into Fe3+, which repeatedly reacted with the H2S and produced more ·OH to enhance the chemodynamic therapy of colorectal tumor. Such a thermosensitive PMFLB which operates in synergy with the colorectal TME opens an alternative avenue for the rational design of multifunctional nano-therapeutic agents.

Reshaping the Tumor Immune Microenvironment Based on a Light-Activated Nanoplatform for Efficient Cancer Therapy.

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO3 /Bi2 WO6 (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h+ )-electron (e- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h+ can trigger the decomposition of H2 O2 to generate O2 for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O2 self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.

Hyalase-Mediated Cascade Degradation of a Matrix Barrier and Immune Cell Penetration by a Photothermal Microneedle for Efficient Anticancer Therapy.

For melanoma with high lethality and metastasis rate, traditional therapy has limited effects; local photothermal therapy (PTT) synergetic with immune therapy for cancer treatment can perhaps improve the situation. However, because of the natural existence of the tumor matrix barrier, the penetration depth of drugs and immune cells often dampens the efficacy of cancer treatment. Herein, we report an innovative synergetic PTT and immune therapy through dissolving microneedles for the codelivery of the hyaluronidase-modified semiconductor polymer nanoparticles containing poly(cyclopentadithiophene-alt-benzothiadiazole) and immune adjuvant polyinosinic-polycytidylic acid (PIC). Benefiting from the dissolution of an extracellular matrix of hyaluronidase, the semiconductor polymer nanoparticles and PIC penetrate the tumor deeply, under synergetic therapy with PTT, activating the immune cells and enhancing the T-cell immune response for inhibition of tumor growth and metastasis. This study provides a promising platform for effective melanoma treatment and a novel strategy to overcome the stromal barrier.