Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis
Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis
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具有高药物负载的智能阿霉素纳米颗粒，可增强化疗抗耐药性和癌症诊断
DOI：
10.1039/c5nr00290g
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发表时间：
2015-01-01
期刊：
影响因子：
6.7
通讯作者：
Zhang, Xiaohong
中科院分区：
文献类型：
--
作者：
Yu, Caitong;Zhou, Mengjiao;Zhang, Xiaohong
阿霉素（doxorubicin，DOX）因其在疗效和价格上的优势而被广泛应用于多种肿瘤的治疗，通常将其包裹在各种纳米载体中作为药物载体。虽然有效，但在大多数基于纳米载体的递送系统中，DOX的药物负载能力相当低;这可导致不期望的全身毒性和排泄问题。在此，我们首次报道了使用纯阿霉素纳米粒（DOX NPs）而不添加任何载体来增强化疗抵抗耐药性。载药量高达90.47%，大大超过了以往的报道。这些PEG稳定的DOX纳米粒表现出良好的生物相容性和稳定性，血液循环时间长，在酸性环境中快速释放和在肿瘤中的高积累。与游离DOX相比，DOX纳米颗粒在抑制细胞和肿瘤生长方面显示出显著增强的抗癌治疗功效。此外，它们还可以容易地与其他抗癌药物结合用于协同化疗以克服癌症的耐药性。DOX的荧光特性也赋予这些纳米颗粒成像能力，从而使其成为诊断和治疗的多功能系统。这项工作证明了DOX NPs在癌症诊断、治疗和克服药物耐受性方面的巨大潜力。
Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.