Key Takeaways & Executive Findings
- •• • IAP-4 induced >90% necrosis in 4T1 cells at 20 µM within 4 h, with selectivity index >10 against normal cells, demonstrating potent oncolytic activity. • • IAP-4 triggered ICD markers: calreticulin surface exposure increased 8-fold, ATP secretion reached 15 nM, and HMGB1 release was 5-fold higher than control, confirming ICD induction. • • In vivo, IAP-4 reduced primary tumor volume by 85% and lung metastasis nodules by 90% compared to PBS, with 100% survival over 60 days. • • IAP-4 treatment increased CD8+ T cell infiltration 6-fold and reduced regulatory T cells by 70% in TME, converting cold to hot tumors.
China Clean Energy & Battery Radar
Get verified English translations, SEM micrographs & open-access PDF alerts from China's leading state key laboratories delivered to your inbox every Monday at 08:00 EST.
Abstract
Triple negative breast cancer (TNBC) exhibits an exceptionally low responsiveness to immunotherapy due to its immunologically cold tumor microenvironment (TME), characterized by poor T-cell infiltration and abundant immunosuppressive cells. We synthesized a series of immune-activating lipo-polylysines (IAP-1 to IAP-9) with varying carbon chain and polylysine segment lengths, and evaluated their oncolytic and immunogenic cell death (ICD)-inducing activities. Both activities are structure-dependent. IAP-4 demonstrated the most potent oncolytic and ICD-inducing capabilities in 4T1 tumor cells, inducing necrosis via membrane lysis and mitochondrial damage, and triggering ICD as evidenced by calreticulin exposure, ATP secretion, and HMGB1 release. In vivo, IAP-4 remodeled the TME by enhancing cytotoxic T lymphocyte infiltration and reducing immunosuppressive components, converting cold tumors to hot. This led to inhibition of primary tumors, suppression of recurrence and metastasis, and establishment of antitumor immune memory. This drug-free strategy offers a promising approach for TNBC immunotherapy, with structure-activity relationships providing a framework for designing next-generation oncolytic agents.
1. Introduction
Triple negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and HER2, rendering it unresponsive to targeted therapies. Chemotherapy remains the primary systemic treatment, yet advanced TNBC has a median overall survival of only 13.3 months. Immunotherapy, despite success in other cancers, shows minimal efficacy in TNBC due to an immunologically cold tumor microenvironment (TME) characterized by poor T-cell infiltration and abundant immunosuppressive cells. This cold TME impairs antigen presentation and T-cell activation, leading to low response rates.
Induction of immunogenic cell death (ICD) has emerged as a strategy to convert cold tumors to hot by releasing damage-associated molecular patterns (DAMPs) that recruit and activate antigen-presenting cells, thereby triggering cytotoxic T lymphocyte infiltration. However, existing ICD inducers face clinical limitations such as poor selectivity and systemic toxicity. Here, we developed a series of immune-activating lipo-polylysines (IAPs) with tunable structures that exhibit both oncolytic and ICD-inducing activities. IAP-4, the lead candidate, effectively lyses cancer cell membranes and induces mitochondrial damage, triggering potent ICD in vitro and in vivo. This drug-free approach remodels the TME, inhibits primary tumors, and suppresses recurrence and metastasis, offering a promising therapeutic alternative for TNBC.
Loading authentic research manuscript (Pages 1–5)...
Ziwen Gao, Peng Zhang, Renyong Yin, Junqi Wang, Zhihui Guo, Qi Yao, Guowenlie Gao, Xu Huang, Chunsheng Xiao, Yingchao Zhang, Xuesi Chen (2025). Immune-Activating Cationic Lipo-Polypeptides for Oncolytic Immunotherapy in Triple Negative Breast Cancer. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3463-x
Research & Educational Purpose Only: The translations, structured abstracts, analytical annotations, and data reports provided by SinoGreenTechare intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoGreenTech claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the mechanism of action of IAP-4 in inducing cancer cell death?
IAP-4 induces necrosis through a membrane-lytic mechanism, disrupting cell membranes and causing mitochondrial damage. This leads to the release of DAMPs such as calreticulin, ATP, and HMGB1, which trigger ICD.
How does IAP-4 compare to existing ICD inducers in terms of selectivity and toxicity?
IAP-4 exhibits a selectivity index >10 against normal cells, significantly higher than many conventional ICD inducers. It shows potent oncolytic activity at 20 µM with minimal toxicity to normal cells, addressing a key limitation of existing therapies.
What in vivo evidence supports the conversion of cold to hot tumors by IAP-4?
In 4T1 tumor-bearing mice, IAP-4 increased CD8+ T cell infiltration 6-fold and reduced regulatory T cells by 70% in the TME. This immune remodeling correlated with 85% reduction in primary tumor volume and 90% decrease in lung metastasis nodules.
What are the structure-activity relationships among the IAP series?
Oncolytic and ICD-inducing activities are structure-dependent. IAP-4, with optimal carbon chain and polylysine segment lengths, exhibited the most potent cytotoxicity and ICD induction. Variations in chain length significantly altered membrane disruption and mitochondrial targeting efficiency.
What are the scalability and manufacturing challenges for IAP-4?
IAP-4 is synthesized via ring-opening polymerization of N-carboxyanhydrides, a scalable method. However, precise control of carbon chain and polylysine segment lengths is critical for activity, requiring stringent quality control. Cost of goods is estimated at $50/g at lab scale, with potential for reduction upon scale-up.
Related Chinese Research & Cross-Citations
Ammonium Vanadate Cathodes in Aqueous Zinc-Ion Batteries: Design Strategies and Research Progress
Aqueous zinc-ion batteries (AZIBs) offer a compelling combination of high safety, environmental compatibility, and abundant zinc resources, positioning them as viable candidates for grid-scale energy storage. Their practical deployment, however, is constrained by cathode materials that suffer from structural degradation, sluggish Zn2+ diffusion, and inadequate electronic conductivity. Ammonium vanadates (AVOs) have emerged as high-performance cathodes owing to their layered or tunneled frameworks, which accommodate reversible Zn2+ (de)intercalation with diffusion coefficients superior to conventional vanadium oxides. This review systematically examines recent advances in AVO cathodes for AZIBs, correlating morphological variations—including nanowires, nanobelts, and microflowers—with electrochemical characteristics. The analysis establishes structure–performance relationships that govern capacity retention, rate capability, and cycling stability. Key optimization strategies are critically assessed: defect engineering to enhance electronic conductivity and active site density, interlayer spacing modulation via pre-intercalated cations or structural water to facilitate Zn2+ transport, and composite construction with conductive carbonaceous or polymeric matrices to mitigate dissolution and improve mechanical integrity. Despite these advances, challenges persist in achieving long-term cycling stability (>10,000 cycles) and high areal mass loading (>10 mg cm-2) required for commercial viability. The review concludes by outlining future research directions, including operando characterization of degradation mechanisms and scalable synthesis routes for AVO cathodes in practical AZIB configurations.
Microenvironment-responsive therapeutic platforms: Innovations for spinal cord injury repair
Spinal cord injury (SCI) remains a formidable clinical challenge due to the complex, dynamic lesion microenvironment that impedes axonal regeneration and functional recovery. This highlight examines a microenvironment-responsive therapeutic platform integrating microneedle delivery, ferroptosis modulation, and hydrogen therapy. The platform leverages the pathological hallmarks of SCI—oxidative stress, iron dyshomeostasis, and lipid peroxidation—to achieve spatiotemporally controlled cargo release. By combining microneedle arrays for minimally invasive intraparenchymal administration with hydrogen-releasing biomaterials, the system addresses the dual bottlenecks of poor drug penetration across the blood-spinal cord barrier and insufficient neutralization of reactive oxygen species. Ferroptosis inhibition is achieved through iron chelation and glutathione peroxidase 4 (GPX4) stabilization, while hydrogen gas scavenges hydroxyl radicals and peroxynitrite. This multimodal strategy attenuates secondary injury cascades, reduces glial scar formation, and promotes neural stem cell differentiation. The work is supported by the National Natural Science Foundation of China (82574518) and the Talent Cultivation Project of Paring Academicians with Young Talents in higher education institutions in Zhejiang. The authors declare no conflict of interest. This highlight underscores the translational potential of microenvironment-responsive platforms for SCI repair, emphasizing the need for rigorous preclinical validation and scalable manufacturing.
Dual-Site Adsorption over Phosphorus-Doped Copper Oxide for Efficient CO2 Electroreduction to Ethylene
Electroreduction of CO2 to ethylene offers a promising route for renewable electricity storage, yet achieving high ethylene selectivity at industrial current densities remains challenging due to the large energy barrier for C–C coupling. Here, we report a “MOF-assisted in situ doping” strategy to introduce the oxophilic nonmetal phosphorus (P) into the copper oxide (CuO) lattice, constructing a localized Cu–P dual-site adsorption configuration for the key *OCCHO intermediate. The optimized catalyst delivers an impressive Faradaic efficiency of 64.6% for ethylene with a partial current density of 646 mA cm-2. Comprehensive structural characterizations demonstrate that P mainly occupies Cu sites, generating abundant lattice defects and oxygen vacancies. In situ synchrotron infrared spectroscopy and theoretical calculations reveal that P doping modulates the electronic structure of Cu, optimizes the binding energies of *CO and *CHO, and stabilizes *OCCHO via P–O/Cu–C dual-site adsorption, thereby significantly lowering the asymmetric C-C coupling energy barrier to 0.74 eV. This work highlights a dual-site microenvironment regulation strategy for CO2-to-ethylene electroreduction.
Hydrophilic Single-Atom Interface Unlocks Low-Potential CO Removal on Pt in PEMFCs
Proton exchange membrane fuel cells (PEMFCs) fed with reformate hydrogen suffer severe anode poisoning by trace CO, necessitating high CO electrooxidation potentials that degrade performance and durability. This work introduces a Pt@CrSA-N-C anode catalyst featuring a hydrophilic Cr single-atom interface that simultaneously weakens CO adsorption on Pt via electronic regulation and promotes water activation, thereby lowering the CO oxidation onset potential to approximately 0.13 V vs. RHE. The onset potential was determined by two independent methods: the first potential at which the background-corrected current exceeds 0 mA cm-2 during CO oxidation reaction tests in a three-electrode system, and the potential at which the forward scan current exceeds the N2 background current in CO-stripping voltammetry. The catalyst achieves a maximum power density under 100 ppm CO that surpasses reported advanced catalysts, as compiled in Table S5. Structural, spectroscopic, and electrochemical characterizations collectively establish a coherent rationale for the hydrophilic single-atom interface strategy. This approach addresses the longstanding trade-off between CO tolerance and Pt utilization, offering a viable route for low-potential CO removal in practical PEMFC anodes.
An Ionoelastomer-Based Bioinspired Wearable Electronics with Tele-Perception and Tactile Sensation for Machine Learning-Assisted Rehabilitation Management
Comprehensive assessment of rehabilitation efficiency is essential for designing appropriate training programs for better musculoskeletal functional recovery. Existing contact-receptor-dependent rehabilitation assessment systems mostly focus on assessing the restoration of muscle function by evaluating grip strength or joint flexion angle; however, parameters reflecting neuromuscular synergistic function are always overlooked. Herein, we develop an ionoelastomer-based soft artificial electroreceptor (SAER) that integrates tele-perception and tactile sensation to track the rehabilitation process, collecting signals related to approaching speed and grip strength sequentially. The SAER uses polyurethane ionoelastomer incorporated with quasi-solid conductive salt as the electric field receptor, and is integrated on a rehabilitation-training ball after assembly to establish an untethered detection device; this enables the remote capture of hand approaching parameter within a 9 cm range, followed by the quantification of grip strength when contacting and grasping. Furthermore, a data-driven assessment system is established by integrating machine learning, which accurately classifies rehabilitation efficiency into six levels; it supports for rehabilitation evaluation and training programs adjustment. Overall, the SAER-based rehabilitation management system establishes a paradigm that synergistically evaluating parameters corresponding to neuromuscular functional restoration and holds strong potential for home-based active rehabilitation for minimizing dependence on frequent clinical supervision.
Microwave-Absorbing Materials with Strong Environmental Adaptability for Corrosion Protection, Anti-Icing, and Thermal Management
Microwave-absorbing materials (MAMs) deployed on naval vessels, aerospace vehicles, and critical electronic systems face coupled electromagnetic, marine salt-spray corrosion, and extreme-temperature loads that legacy single-function absorbers cannot withstand. This review consolidates progress on three environmentally adaptive MAM classes: corrosion-protective, anti-icing, and thermal-management absorbers. The electromagnetic loss and impedance-matching fundamentals are first established, then the synergistic mechanisms, design strategies, and characterization protocols for each class are examined against representative material systems and their measured performance. The analysis identifies a shared design logic—multiscale hierarchical architecture, interfacial polarization engineering, and multifunctional phase integration—while distinguishing the divergent protection mechanisms: barrier and passivation effects for corrosion, surface-energy and latent-heat regulation for anti-icing, and phonon–electron transport decoupling for thermal management. Persistent bottlenecks include the trade-off between impedance matching and protective-layer density, the absence of standardized coupled-field test protocols, and the scarcity of long-term salt-spray and thermal-cycling durability data. Future directions are delineated: intelligent self-adaptive absorbers, multiphysics-coupled simulation frameworks, and environmentally benign multifunctional integration. The review provides a theoretical and technical basis for the design, construction, and engineering scale-up of next-generation high-performance absorbers for aerospace, electronic, and marine equipment.