The relevance of personalized medicine has inspired research for individually concerted diagnosis and therapy. Numerous efforts are devoted to designing drug particulates with capabilities of tumor penetrating and subcellular trafficking to concurrently discharge theranostics in response to multistimulations. In this study, a bioinspired particulate, formulated with whole components of native high‐density lipoproteins (HDLs) and decorated with the tumor‐penetrating peptide iRGD, is proposed to promote tumor penetration of HDLs (pHDLs) together with payloads. Specifically, paclitaxel (PTX), and the NIR fluorescent probe indocyanine green (ICG) are integrated into pHDLs (pHDL/PTX‐ICG) for synergetic chemo‐phototherapy. Inspired by lipoproteins, pHDLs are not only restored from naturally occurring materials but also possessed artificially endowed functions, leading to an enhanced cellular uptake, higher accumulation, and deep penetration into tumors without causing appreciable adverse effects, compared to reconstituted HDLs or lipid‐based nanoparticles. After intravenous administration, pHDL/PTX‐ICG performs a burst of intracellular drug release and imaging‐guided precision chemo‐phototherapy upon NIR irradiation that completely eradicates xenograft tumors. Neither recurrence nor significant toxicity is observed due to maneuvered regional photodynamic and photothermal therapy. Taken together, pHDL/PTX‐ICG is proven to be a promising platform to achieve deep tumor penetration and imaging‐guided chemo‐phototherapy.

中文翻译：

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深入肿瘤的生物微粒可激发突发的细胞内药物释放，从而实现精确的化学光疗。

个性化医学的相关性激发了针对个体协调诊断和治疗的研究。许多努力致力于设计具有肿瘤穿透能力和亚细胞运输能力的药物颗粒，以响应多种刺激同时释放治疗药物。在这项研究中，提出了一种由生物启发的微粒，该微粒由天然高密度脂蛋白（HDL）的全部成分配制而成，并用穿透肿瘤的肽iRGD修饰，可促进HDL（pHDLs）和有效载荷的肿瘤渗透。具体来说，紫杉醇（PTX）和NIR荧光探针吲哚菁绿（ICG）已整合到pHDL（pHDL / PTX-ICG）中，用于协同化学光疗。受脂蛋白的启发，与重构的HDLs或基于脂质的纳米颗粒相比，pHDLs不仅可以从天然物质中恢复，而且还具有人为赋予的功能，从而导致细胞摄取增加，积累更多，并深入肿瘤内而不会引起明显的不良影响。静脉内给药后，pHDL / PTX-ICG会在NIR照射下进行细胞内药物释放和影像引导的精密化学光疗，彻底消除异种移植肿瘤。由于进行了局部光动力和光热疗法，因此未观察到复发或明显的毒性。总之，pHDL / PTX-ICG被证明是实现深层肿瘤渗透和影像引导化学光疗的有前途的平台。与重构的HDL或基于脂质的纳米颗粒相比，它可以深入肿瘤，而不会引起明显的不良影响。静脉内给药后，pHDL / PTX-ICG会在NIR照射下进行细胞内药物释放和影像引导的精密化学光疗，彻底消除异种移植肿瘤。由于进行了局部光动力和光热疗法，因此未观察到复发或明显的毒性。总之，pHDL / PTX-ICG被证明是实现深层肿瘤渗透和影像引导化学光疗的有前途的平台。与重构的HDL或基于脂质的纳米颗粒相比，它可以深入肿瘤，而不会引起明显的不良影响。静脉内给药后，pHDL / PTX-ICG会在NIR照射下进行细胞内药物释放和影像引导的精密化学光疗，彻底消除异种移植肿瘤。由于进行了局部光动力和光热疗法，因此未观察到复发或明显的毒性。总之，pHDL / PTX-ICG被证明是实现深层肿瘤渗透和影像引导化学光疗的有前途的平台。pHDL / PTX-ICG在NIR照射下进行细胞内药物释放和影像引导的精密化学光疗，彻底消除了异种移植肿瘤。由于进行了局部光动力和光热疗法，因此未观察到复发或明显的毒性。总之，pHDL / PTX-ICG被证明是实现深层肿瘤渗透和影像引导化学光疗的有前途的平台。pHDL / PTX-ICG在NIR照射下进行细胞内药物释放和影像引导的精密化学光疗，彻底消除了异种移植肿瘤。由于进行了局部光动力和光热疗法，因此未观察到复发或明显的毒性。总之，pHDL / PTX-ICG被证明是实现深层肿瘤渗透和影像引导化学光疗的有前途的平台。