Core Viewpoint - Cancer remains a leading cause of death globally, prompting the search for new targeted therapies, particularly antibody-drug conjugates (ADCs) which show promise in delivering chemotherapy directly to cancer cells while minimizing side effects [2][3]. Group 1: Current ADC Limitations - Current ADCs have a drug-to-antibody ratio (DAR) of only 2-8, limiting the range of chemotherapy drugs that can be used, as only highly potent drugs can be selected [2][6]. - The limited DAR means that ADCs cannot utilize a broader spectrum of less potent chemotherapy drugs, which constrains treatment options [6]. Group 2: Introduction of ABC Technology - The newly developed antibody-bottlebrush prodrug conjugates (ABC) offer modular synthesis and a significantly higher DAR, allowing for a wider range of effective payloads, including less potent chemotherapy drugs [3][9]. - ABC technology enables the delivery of hundreds of prodrug molecules via a single antibody, enhancing the customization and diversity of drug combinations [8][9]. Group 3: Experimental Results - In preclinical models, ABCs demonstrated superior efficacy in eliminating tumors compared to traditional ADCs and non-targeted prodrugs, even at very low doses [13][14]. - The study showed that ABCs outperformed FDA-approved ADCs like T-DXd and TDM-1, indicating a potential for enhanced treatment outcomes [14]. Group 4: Future Directions - The research team plans to explore combinations of different chemotherapy drugs with varying mechanisms to improve overall efficacy [14]. - There is potential for using various monoclonal antibodies, as over 100 have been approved, to create new targeted cancer therapies through the ABC platform [14].

Core Viewpoint - The research highlights that chemotherapy can awaken dormant disseminated tumor cells (DTCs) in lung cancer, leading to metastatic recurrence, and proposes a novel combination therapy strategy to inhibit this process [2][4][8]. Group 1: Research Findings - The study established a dormant tumor cell lineage tracing system called DormTracer, confirming that dormant DTCs can be reactivated by chemotherapy, resulting in metastatic recurrence [5][6]. - Chemotherapy drugs, including doxorubicin and cisplatin, enhance the proliferation and lung metastasis of dormant breast cancer cells [4][6]. - The mechanism involves chemotherapy inducing senescence in fibroblasts, which promotes the formation of neutrophil extracellular traps (NETs) that facilitate the proliferation of dormant DTCs [5][6]. Group 2: Proposed Treatment Strategy - The research suggests a new combined treatment strategy using senolytic drugs (dasatinib + quercetin) alongside chemotherapy to inhibit the reactivation of dormant DTCs and suppress tumor metastasis [5][6][8]. - This combination therapy aims to improve treatment outcomes by addressing the adverse effects of chemotherapy on cancer metastasis [8].

Core Viewpoint - The development of a programmable magnetic field-driven bio-inspired hydrogel fiber robot offers a novel, non-invasive, and precise method for targeted drug delivery in the treatment of intracranial tumors, particularly those located near critical brain areas [1][5]. Group 1: Technology and Innovation - The research team has created a hydrogel fiber robot inspired by the movement of nematodes, capable of multi-modal movement in the narrow subarachnoid space of the brain [2][3]. - The hydrogel fiber robot is made from a mixture of the animal's own blood and magnetic particles, ensuring biocompatibility and flexibility, which allows it to navigate through tight spaces without causing damage to surrounding tissues [2][3]. - The robot can perform various movements such as swinging, crawling, and rolling, controlled by an external programmable magnetic field [3]. Group 2: Drug Delivery Mechanism - The robot utilizes a high-frequency alternating magnetic field to induce fragmentation for drug release, allowing for targeted delivery of chemotherapy drugs like doxorubicin [4]. - The drug delivery mechanism is designed to be responsive to magnetic field parameters, enabling precise control over the drug release rate, thus avoiding the toxicity associated with traditional chemical triggers [4][5]. Group 3: Clinical Application and Efficacy - In a study involving 18 miniature pigs with glioma models, the treatment group using the drug-loaded hydrogel fiber robot showed a tumor size reduction of four times compared to the control group after 26 days [5]. - The hydrogel fiber robot is customized from the patient's own blood, minimizing immune rejection and allowing for automatic degradation post-treatment, eliminating the need for surgical removal [5]. - The innovative combination of bio-inspired movement, real-time X-ray imaging, and magnetic-responsive drug release presents a transformative approach for non-invasive treatment of deep-seated brain tumors [5].

Group 1 - The core idea of the research is the development of a "protein cage" that can encapsulate cytotoxic drugs used in chemotherapy, enhancing their targeted delivery and reducing side effects [1][2] - The research is led by Dr. Taylor Szyszka and Associate Professor Yu Heng Lau from the University of Sydney, and the findings have been published in the journal "Angewandte Chemie International Edition" [1] - The protein cage, specifically a subclass known as "shelled protein," was initially discovered in bacteria in compost in 2019 and is characterized by its stability and ability to protect its contents [1][2] Group 2 - The researchers successfully encapsulated the chemotherapy drug doxorubicin within the enhanced shelled protein, marking the first successful assembly of this type [2] - The previous method of loading drugs into shelled proteins was inefficient and compromised stability, as it required disassembly and reassembly [2] - Future research will focus on modifying the protein structure to enable the shelled protein to recognize and enter specific cells, such as liver cells for liver disease treatments [4]