Rationale: Insufficient penetration and accumulation of theranostic payloads in solid tumors greatly challenge the clinical translation of cancer nanomedicines. To address this challenge, we synthesized natural melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets with good biocompatibility and self-assembling ability./nMethods: We used an opto-acoustic synergistic irradiation (OASI) method that was effective at lower energy levels than ultrasound- or laser-only irradiation to safely vaporize the nanodroplets and to cavitate the generated microbubbles for mechanically enhancing intratumoral delivery. The delivered melanin and doxorubicin inside the tumors mediated secondary chemo-photothermal therapy under laser irradiation to fully kill cancer cells./nResults: In vivo animal experiments demonstrated direct mechanical disruption of tumor structures (H&E staining), enhanced intratumoral penetration of melanin (photoacoustic imaging), and efficient intratumoral accumulation of doxorubicin (fluorescent imaging). Anti-tumor experiments demonstrated that the nanodroplets combined with OASI treatment and subsequent laser irradiation could efficiently eliminate melanoma tumors./nConclusion: Melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets hold great promise for translational sono-chemo-photothermal cancer therapy.

中文翻译：

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光声协同辐射以安全的能量水平和有效的声波化学光热癌症疗法汽化天然黑色素为核心的纳米液滴。

原理：实体肿瘤中穿刺治疗有效载荷的渗透和积累不足，极大地挑战了癌症纳米药物的临床翻译。为了应对这一挑战，我们合成了具有良好生物相容性和自组装能力的天然黑色素核和阿霉素负载的全氟戊烷纳米滴。/n方法：我们使用了一种光声协同辐射（OASI）方法，该方法在比仅超声或激光照射可安全蒸发纳米液滴并使空化的微泡空化，从而机械增强肿瘤内递送。在激光照射下，肿瘤内部传递的黑色素和阿霉素介导了二次化学光热疗法，以完全杀死癌细胞。 体内动物实验证明了肿瘤结构的直接机械破坏（H＆E染色），黑色素的瘤内穿透增强（光声成像）和阿霉素的瘤内有效积聚（荧光成像）。抗肿瘤实验表明，纳米滴与OASI治疗相结合并随后进行激光照射可以有效消除黑色素瘤肿瘤。/n结论：黑色素为核心且阿霉素负载的全氟戊烷纳米滴为声波转化化学光热癌症治疗具有广阔的前景。