Janus AuNR-Pt Nanoscale Motors for EnhancedNIR-II Photoacoustic Imaging of Deep Tumorsand Pt2+ Ion-related Chemotherapy

Research Abstract

Nanomotors have active locomotion capabilities and thus have great potential for deep tissue imaging and in vivo drug delivery. The use of nanomotors with particle sizes smaller than 100 nm for in vivo imaging and therapy is one of the core innovations in this field. Here, hydrogen peroxide (H₂O₂)-driven nanoscale Janus gold nanorod-platinum (JAuNR-Pt) nanomotors were used to enhance the effectiveness of NIR-II for area photoacoustic (PA) imaging and tumor therapy in deep tumor tissues . The JAuNR-Pt nanomotors deposited a platinum Pt shell on one end of the gold nanorods with coverages including 10%, 25%, 50%, 75%, and 100%. Among them, the JAuNR-Pt nanomotor with 50% platinum shell coverage exhibits the highest diffusion coefficient (De) and can move rapidly in the presence of hydrogen peroxide. Self-propulsion of JAuNR-Pt nanomotors enhanced cellular uptake, accelerated lysosomal escape, and facilitated sustained release. Cytotoxic Pt²⁺ ions enter the nucleus, leading to DNA damage and apoptosis. JAuNR-Pt nanomotors exhibited deep penetration and accumulation in tumors and high tumor therapeutic efficacy. Therefore, the findings of this study demonstrate significant tumor imaging and antitumor effects, providing an effective strategy for accurate diagnosis and treatment of the disease.

Schematic illustration of the fabrication of JAuNR-Pt nanomotors and their NIR-II photoacoustic imaging and antitumor effects in deep tumor tissues. (a) Schematic diagram of the synthetic route of the JAuNR-Pt nanomotor. It is made of Pt nanoshells partially deposited on one end of the AuNR. The direct contact between AuNRs and Pt nanoshells, in the presence of H₂O₂, transfers electrons from Pt to AuNRs, resulting in rapid self-motion towards the Pt side via self-electrophoresis. (b) JAuNR-Pt nanomotor for in vivo NIR-II photoacoustic imaging and cancer therapy. H₂O₂-driven JAuNR-Pt nanomotors trigger dual behaviors: enhanced cellular uptake and accelerated lysosomal escape (via automobility), while simultaneously generating large amounts of Pt²⁺ ions (as a Pt²⁺ ion pool) for high cytotoxicity. NIR-II photoacoustic imaging is used to track nanomotor motion in vivo, providing rich information for deep tumor imaging and therapy.

At present, chemotherapy is still one of the most commonly used methods in clinical cancer treatment. Chemotherapy, usually administered orally or intravenously, works throughout the body and has many advantages in inhibiting the spread of cancer cells and preventing tumor recurrence. Cisplatin is the most widely used drug in chemotherapy, but its clinical application is severely limited by drug resistance and side effects. Platinum (Pt) nanomaterials/nanoclusters are based on a platinum ion (Pt²⁺) release mechanism with the ability to kill cancer cells and avoid platinum resistance. Pt is easily oxidized to Pt²⁺ ions in the tumor microenvironment. Pt²⁺ ions more easily enter the nucleus and bind to DNA, leading to irreversible DNA damage and apoptosis. Pt nanomaterials have the following advantages as anti-tumor drugs: (1) compared with small molecule drugs, they can effectively bypass the efflux pathway in cancer cells; (2) the surface of Pt nanomaterials is easily affected by thiol-polyethylene Molecular modification such as glycol thiol (HS-PEG) to improve their biocompatibility and increase their enrichment in tumors; (3) Pt nanomaterials with large specific surface area and many surface atoms are easily oxidized, thereby releasing Pt²⁺ ions, effectively kill cells. Currently, a problem limiting the in vivo processing of Pt nanomaterials is that they rely only on passive in vivo transport, resulting in low drug absorption rates and difficult deep tumor enrichment. Another problem is that once the amount of Pt²⁺ ions delivered to DNA or DNA-Pt plus complexes is insufficient to induce cell death, Pt resistance may develop. Nanocarrier-based drug delivery systems can increase the Pt²⁺ drug loading, Pt The potential emergence of resistance is thus overcome to improve the efficacy of chemotherapy and reduce systemic toxicity. Actively moving micro/nanomotors exhibit stronger interactions with cells and show great potential in enhancing cellular uptake. Although it has been reported that a motor with voluntary movement can promote its penetration in tissues, whether such active movement can effectively enhance its accumulation in deep tumors in vivo and achieve effective platinum-based chemotherapy has not been reported.

Hereby, researchers developed a nanohydrogen peroxide (H₂O₂)-driven Janus gold nanorod-platinum (JAuNR-Pt) nanomotor that not only actively moves to the deep tissues of tumors, but also persists in the tumor microenvironment Release Pt²⁺ ions, thereby enabling effective tumor therapy. The nanomotor consists of a Pt nanoshell deposited on one end of the AuNR, which exhibits a strong NIR-II PA imaging signal (Figure 1). In the JAuNR-Pt nanomotor, the direct contact between AuNR and Pt nanoshell enables electron transfer from Pt nanoshell to AuNR in the presence of H₂O₂, thereby exhibiting fast autonomous motion. The self-motor behavior of JAuNR-Pt nanomotors can enhance cellular uptake and accelerate lysosomal escape, making it more enriched around the nucleus. At the same time, it can be used as a Pt²⁺ ion pool to transport a large amount of Pt²⁺ ions to the nucleus for a long time, induce irreversible DNA damage, and overcome Pt drug resistance. The NIR-II PA imaging of the tumor reflects that the JAuNR-Pt nanomotor enhances the penetration of tumor tissue in vivo, showing excellent tumor therapeutic effect. We propose an effective strategy to utilize nanoscale nanomotors with autonomous propulsion capability for improved tissue penetration and durable treatment via Pt-based chemotherapy.