A Pectin-Based Delivery Nanoplatform with an Optimized Tradeoff between Active Targeting and Drug Loading for Hepatocellular Carcinoma Treatment.

The presence of multivalent reactive groups in the structure of natural polysaccharides enables diverse modifications toward advanced nanomedicines with integrated functionalities for enhanced cancer therapy; therefore, a polysaccharide-based nanoplatform with an optimized trade-off between multifunctionalities for a maximized therapeutic efficiency has been always a long-term research interest, which, however, remains relatively unexplored. We report herein pectin-based delivery nanoplatforms with an optimized trade-off between active targeting and drug loading for chemo-immunotherapy of hepatocellular carcinoma (HCC). Specifically, the targeting moiety of pectin, galactose, is subjected to partial oxidization to an aldehyde function that enables the simultaneous modulation of active targeting properties and drug conjugation capacity by the degree of oxidation, affording pectin-based polymer prodrugs OP2-DOX, OP6-DOX, and OP10-DOX with three different degrees of oxidation.

The role of redox homeostasis in tumor progression: implications for cancer therapy.

The dynamic balance of reduction-oxidation (redox) plays a vital role in maintaining normal physiological functions, such as metabolism, cell differentiation, immune response, and cell death. The disruption of redox homeostasis in tumor cells leads to more adverse damage than that in normal tissues because of the significantly higher redox level resulting from the high metabolic characteristics of tumor tissue. However, tremendous efforts based on the regulation of redox homeostasis are still hampered by the enhanced antioxidant capability of tumor cells during treatment.

A Self-Adaptive Rhodium(I) Complex-Based Nanoplatform with Type II Immunogenic Cell Death for Near-Infrared Phosphorescence Imaging and Cancer Immunotherapy.

Despite immunogenic cell death (ICD) has garnered significant attention in cancer therapy, achieving precise in vivo immunity activation and simultaneous visualization of immunotherapy processes remain significant challenges due to the difficulties in facile integration of multifunctionalities in a single nanomedicine. For this purpose, herein a self-adaptive rhodium(I) complex-based nanoplatform driven by metallophilic interactions is reported not only for near-infrared (NIR) imaging-guided cancer immunotherapy, but also as the first example of a rhodium(I)-based ICD inducer. Specifically, this nanoplatform enables high tumor enrichment by utilizing homologous targeting capability camouflaged by cancer cell membranes and facilitates enhanced in vivo NIR phosphorescence imaging.

Rhodium-based metallodrugs for biological applications: current status and future perspectives.

Metal complexes represent a promising avenue in drug research and development, exemplified by metallodrugs including cisplatin, carboplatin, and oxaliplatin that have been clinically approved for the treatment of various solid tumors. However, most of the reported metallodrugs suffer from compromised therapeutic efficacy due to multidrug resistance (MDR) and severe systemic toxicity. Rhodium is another useful member of the platinum group metals in addition to the extensively explored platinum, whose complexes have attracted increasing attention in bioinorganic and medicinal chemistry not only for their low oxophilicity, broad functional-group tolerance, and superior catalytic performance, but also for their intriguing self-assembly behaviors and photophysical properties arising from the intermolecular metallophilic interactions.

Biomimetic Delivery of Cisplatin for Efficient Immunotherapy of Gasdermin E-Positive Hepatocellular Carcinoma via a Pt Concentration-Dependent Minimalist Pyroptosis Strategy.

Compared to the classical Gasdermin D (GSDMD)-mediated pyroptosis that has been extensively explored for cancer immunotherapy, the direct induction of Gasdermin E (GSDME) pyroptosis has been rarely reported, likely due to the well-recognized reduced GSDME levels in solid tumors. This study reports the use of a milestone chemotherapeutic drug, cisplatin (CDDP), for effectively inducing inflammatory pyroptosis that depends on the intracellular platinum (Pt) concentration in GSDME-positive hepatocellular carcinoma identified by bioinformatic analyses. Biomimetic delivery of CDDP via an internalizing arginine-glycine-aspartic acid (iRGD)-functionalized plasma exosome (iRGD-Pla-Exo) guarantees an effective tumor intracellular Pt concentration above the threshold for inducing prompt and potent pyroptosis with significantly compromised systematic side effects.

A robust metal-organic framework-based nanozyme with multienzyme-like properties for synergistic tumor therapy via efficient and sustainable Nitric oxide generation.

Nitric oxide (NO)-based gas therapy represents an emerging strategy for cancer treatment, which, however, still suffers from insufficient intracellular NO production for compromised therapeutic efficiency due to limited endogenous hydrogen peroxide (HO) concentration and relatively slow NO generation rate. The use of metal-organic framework (MOF) with highly ordered porous structure and functional adjustability to design a multienzyme-like nanozyme provides a simple yet reliable approach for efficient and sustainable NO generation. Herein, a MOF-based nanozyme with multienzyme-like properties is constructed by depositing ultrasmall gold nanoparticles (Au NPs) and subsequently loading a NO donor, l-arginine (l-Arg) on an iron porphyrin integrated MOF, which enables efficient and sustainable NO generation for synergistic tumor therapy.

A Metformin-Based Multifunctional Nanoplatform as a DNA Damage Amplifier for Maximized Radio-Immunotherapy to Overcome Radiotherapy Resistance.

Radiotherapy (RT) has been highlighted to be an effective strategy for antitumor immunity activation by causing direct DNA damages, but it generally suffers from low response rates due to the compromised cytosolic DNA (cDNA) recognition by cyclic GMP-AMP synthase (cGAS). Simultaneous DNA repair and clearance system regulation for enhanced cDNA accumulation is a useful approach to improve immune response rates, which remains seldom reported to our knowledge. Here, we report the construction of a metformin (MET)-based multifunctional nanocomplex, CS-MET/siTREX1 (CSMT), consisting of biguanide-decorated CS (CS-MET) as the vector and 3'-5' DNA exonuclease TREX1 siRNA (siTREX1) as the therapeutic gene for RT-induced antitumor immunity enhancement by amplifying the initial DNA damage signals.

Facile integration of a binary nano-prodrug with αPD-L1 as a translatable technology for potent immunotherapy of TNBC.

Immune checkpoint blockers (ICBs)-based immunotherapy is a favorable approach for efficient triple-negative breast cancer (TNBC) treatment. However, the therapeutic efficacy of ICBs is greatly compromised by immunosuppressive tumor microenvironments (TMEs) and low expression levels of programmed cell death ligand-1 (PD-L1). Herein, we constructed an amphiphilic prodrug by linking a hydrophobic STING agonist, MSA-2 and a hydrophilic chemotherapeutic drug, gemcitabine (GEM) via an ester bond, which can self-assemble into GEM-MSA-2 (G-M) nanoparticles (NPs) with a tumor growth inhibition (TGI) value of 87.

Peptide core spherical nucleic acids circumvent tumor immunosuppression via supplementing methionine for enhanced photodynamic/gene immune/therapy of hepatocellular carcinoma.

Spherical nucleic acids (SNAs) with functional peptide cores are an emerging nanoplatform for synergistic cancer therapy but have been rarely reported. We construct herein the first SNA nanoplatform based on a biodegradable binary peptide backbone of methionine (Met) and cysteine (Cys) for codelivery of a photosensitizer, Chlorin e6 (Ce6) and human liver-specific miR122 for synergistic photodynamic-gene therapy of hepatic cell carcinoma (HCC). Met supplementation by the peptide core improves the infiltration of T cells and enhances the effector function of T cells for turning a "cold" tumor into a "hot" one.

Hydrogel-based cardiac patches for myocardial infarction therapy: Recent advances and challenges.

Myocardial infarction (MI) remains the leading cause of death related to cardiovascular diseases globally, presenting a significant clinical challenge due to the specificity of the lesion site and the limited proliferative capacity of cardiomyocytes (CMs) for repairing the infarcted myocardium. Extensive studies reported so far has focused on the utilization of hydrogel-based cardiac patches for MI treatment, highlighting their promising mechanical properties, conductivity, and ability to remodel the microenvironment post-repair. However, the majority of developed cardiac patches have been limited to the myocardial tissue surface via suturing or adhesive administration.

Histidine phosphatase-ferroptosis crosstalk modulation for efficient hepatocellular carcinoma treatment.

Altering the mechanisms of tumor cell death and overcoming the limitations of traditional chemotherapy is pivotal to contemporary tumor treatment. Inducing ferroptosis, while circumventing safety concerns associated with ferrous vectors, through nonferrous ferroptosis is a promising but underexplored frontier in cancer therapy. Histidine phosphatase (LHPP) has emerged as a novel therapeutic target in treating hepatocellular carcinoma (HCC), but the precise mechanism of LHPP against HCC remains unclear.

Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery.

Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives.

A Programmable Microfluidic Paper-Based Analytical Device for Simultaneous Colorimetric and Photothermal Visual Sensing of Multiple Enzyme Activities.

New strategies for the simultaneous and portable detection of multiple enzyme activities are highly desirable for clinical diagnosis and home care. However, the methods developed thus far generally suffer from high costs, cumbersome procedures, and heavy reliance on large-scale instruments. To satisfy the actual requirements of rapid, accurate, and on-site detection of multiple enzyme activities, we report herein a smartphone-assisted programmable microfluidic paper-based analytical device (μPAD) that utilizes colorimetric and photothermal signals for simultaneous, accurate, and visual quantitative detection of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE).

Enhancing myocardial infarction treatment through bionic hydrogel-mediated spatial combination therapy via mtDNA-STING crosstalk modulation.

Myocardial infarction (MI)-induced impaired cardiomyocyte (CM) mitochondrial function and microenvironmental inflammatory cascades severely accelerate the progression of heart failure for compromised myocardial repair. Modulation of the crosstalk between CM mitochondrial DNA (mtDNA) and STING has been recently identified as a robust strategy in enhancing MI treatment, but remains seldom explored. To develop a novel approach that can address persistent myocardial injury using this crosstalk, we report herein construction of a biomimetic hydrogel system, Rb1/PDA-hydrogel comprised of ginsenoside Rb1/polydopamine nanoparticles (Rb1/PDA NPs)-loaded carboxylated chitosan, 4-arm-PEG-phenylboronic acid (4-arm-PEG-PBA), and 4-arm-PEG-dopamine (4-arm-PEG-DA) crosslinked networks.

Immunomodulatory Peptides for Tumor Treatment.

Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized.

A fully biodegradable spherical nucleic acid nanoplatform for self-codelivery of doxorubicin and miR122 for innate and adaptive immunity activation.

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa-DOX-miR122 that can self-assemble into stabilized SNA.

An "All-In-One" Immunomodulator-Engineered Clinical Translatable Immunotherapy of Advanced Hepatocellular Carcinoma.

Clinical treatment of advanced hepatocellular carcinoma (HCC) remains a significant challenge. Utilizing 1-bromoacetyl-3,3-dinitroazetidine (RRx-001) to downregulate the expression of innate immune checkpoint molecule, cluster of differentiation 47 (CD47), provides a powerful means for treating advanced HCC containing abundant immunosuppressive macrophages. Herein engineering of a previously optimized Doxorubicin (DOX)-delivery nanoplatform based on sodium alginate is reported to further co-deliver RRx-001 (biotinylated aldehyde alginate-doxorubicin micelle prodrug nanoplatform, BEA-D@R) for efficient immunotherapy of advanced HCC.

Injectable hydrogels as emerging drug-delivery platforms for tumor therapy.

Tumor therapy continues to be a prominent field within biomedical research. The development of various drug carriers has been propelled by concerns surrounding the side effects and targeting efficacy of various chemotherapeutic drugs and other therapeutic agents. These carriers strive to enhance drug concentration at tumor sites, minimize systemic side effects, and improve therapeutic outcomes.

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms.

Gene therapy is a revolutionary treatment approach in the 21st century, offering significant potential for disease prevention and treatment. However, the efficacy of gene delivery is often compromised by the inherent challenges of gene properties and vector-related defects. It is crucial to explore ways to enhance the curative effect of gene drugs and achieve safer, more widespread, and more efficient utilization, which represents a significant challenge in amplification gene therapy advancements.

Liposome-based nanomedicine for immune checkpoint blocking therapy and combinatory cancer therapy.

The discovery of immune checkpoint (IC) has led to a wave of leap forward in cancer immunotherapy that represents probably the most promising strategy for cancer therapy. However, the clinical use of immune checkpoint block (ICB) therapy is limited by response rates and side effects. A strategy that addresses the limitations of ICB therapies through combination therapies, using nanocarriers as mediators, has been mentioned in numerous research papers.

Current advances in modulating tumor hypoxia for enhanced therapeutic efficacy.

Hypoxia is a common feature of most solid tumors, which promotes the proliferation, invasion, metastasis, and therapeutic resistance of tumors. Researchers have been developing advanced strategies and nanoplatforms to modulate tumor hypoxia to enhance therapeutic effects. A timely review of this rapidly developing research topic is therefore highly desirable.

Engineered cyclodextrin-based supramolecular hydrogels for biomedical applications.

Cyclodextrin (CD)-based supramolecular hydrogels are polymer network systems with the ability to rapidly form reversible three-dimensional porous structures through multiple cross-linking methods, offering potential applications in drug delivery. Although CD-based supramolecular hydrogels have been increasingly used in a wide range of applications in recent years, a comprehensive description of their structure, mechanical property modulation, drug loading, delivery, and applications in biomedical fields from a cross-linking perspective is lacking. To provide a comprehensive overview of CD-based supramolecular hydrogels, this review systematically describes their design, regulation of mechanical properties, modes of drug loading and release, and their roles in various biomedical fields, particularly oncology, wound dressing, bone repair, and myocardial tissue engineering.

A multivalent polyphenol-metal-nanoplatform for cascade amplified chemo-chemodynamic therapy.

Chemodynamic therapy (CDT), as an emerging therapeutic strategy, kills cancer cells by converting intracellular hydrogen peroxide (HO) into cytotoxic oxidizing hydroxyl radicals (⋅OH). However, the therapeutic efficiency of CDT is compromised due to the insufficient endogenous HO and metal catalysts in tumor cells. The use of multivalent polyphenols with multiple hydroxyl functions provides a facile yet robust means for efficient CDT augmentation.

A smartphone-integrated portable platform based on polychromatic ratiometric fluorescent paper sensors for visual quantitative determination of norfloxacin.

The emergence of "superbugs" due to antibiotics overuse poses a significant threat to human health and security. The development of sensitive and effective antibiotics detection is undoubtedly a prerequisite for addressing antibiotics overuse-associated issues. However, current techniques for monitoring antibiotics typically require costly equipment and well-trained professionals.