Exploration and application of treating OSCC by a precisely concentrated synergistic agent in combination with thermally responsive release of effective therapeutic dosages of cisplatin

• Discovery of Synergistic Combination: 17AAG , evaluated in detail with cisplatin in OSCC , exhibits remarkable synergism with a wide range of cisplatin concentrations, ensuring robust therapeutic effects. • Hybrid Membrane Strategy for Enhanced Targeting: A hybrid membrane strategy is employed, encapsulating cisplatin and photosensitizers simultaneously, enhancing cisplatin's targeting precision and enabling responsive tracking and release. • Personalized Tumor Therapy Potential: Altering tumor cell membrane type and composition ratio significantly modifies targeting profile of hybrid membrane, suggesting potential of cell membrane-modified nanocarriers for personalized therapy. • Novel treatment strategy for OSCC：A new strategy that combines the synergistic effects of cisplatin and 17AAG, enhanced targeting by mixed membranes, and controlled release, aiming to improve efficacy and reduce systemic toxicity. Platinum-based drugs, foremost among them Cisplatin (CDDP), currently constitute the primary line of chemotherapy for the treatment of oral squamous cell carcinoma (OSCC). However, the extensive utilization of these drugs often results in undesirable systemic toxic side effects. Consequently, in clinical practice, emphasis has shifted towards the adoption of combination drug strategies, aimed at minimizing the dosage of platinum-based drugs while preserving optimal anti-tumor efficacy. Prior research has concentrated on the co-loading of drugs with synergistic potential into a unified nanosystem, yet this approach does not guarantee that the drugs will remain within the concentration range necessary for synergistic effects following nanocarrier release, thus limiting the full exploitation of their synergistic anti-tumor properties. This study has pioneered the discovery that the HSP90 inhibitor 17AAG exhibits remarkable synergistic effects with CDDP in the treatment of OSCC. Importantly, 17AAG can allow CDDP to still exert effective tumor killing effects at lower concentrations. Furthermore, specific concentrations of 17AAG demonstrate synergistic effects with a wide range of CDDP concentrations, positioning it as a promising candidate for the sustained synergistic augmentation of CDDP released from nanocarriers. Additionally, we have augmented CDDP targeting through the employment of a hybrid membrane strategy, encapsulating CDDP and photosensitizers concurrently. This approach enhances CDDP’s targeting precision and enables responsive tracking and release. Notably, we have observed that altering the tumor cell membrane type significantly modifies the tumor targeting profile of the hybrid membrane, suggesting that cell membrane-modified nanocarriers have potential value in achieving personalized tumor therapy. In summary, we have formulated a novel CDDP-based targeted therapy strategy for OSCC, which holds promising implications for future treatment of this malignancy.