Plasmonic nanobubbles rapidly detect and destroy drug-resistant tumors.

Plasmonic nanobubbles rapidly detect and destroy drug-resistant tumors.
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DOI:
10.7150/thno.5116
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发表时间:
2012
期刊:
影响因子:
12.4
通讯作者:
Lapotko DO
Lapotko DO
中科院分区:
医学1区
文献类型:
--
作者:
Lukianova-Hleb EY;Ren X;Townley D;Wu X;Kupferman ME;Lapotko DO

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肿瘤切除术后残留癌细胞对辅助放化疗的抗性导致高复发率和高非特异性组织毒性,从而阻止了头颈部鳞状细胞癌(HNSCC)等癌症的成功治疗。因此,患者的生存率和生活质量取决于辅助治疗的有效性、选择性和低非特异性毒性。我们报告了一种新的治疗诊断体内技术,该技术将声学诊断和抗肿瘤药物(脂质体封装的阿霉素,Doxil)的引导细胞内递送结合在一个快速过程中,即脉冲激光激活的等离子体纳米泡(PNB)。用金纳米颗粒缀合物、Doxil和低能量的单一近红外激光脉冲治疗携带HNSCC的小鼠。肿瘤特异性的金纳米颗粒簇(固体金球)将光脉冲转换为局部PNB。PNB的声信号对肿瘤的检测具有较高的特异性和敏感性。与Doxil脂质体共定位的PNB的机械冲击选择性地将药物喷射到癌细胞的细胞质中。PNB的癌细胞特异性产生及其与Doxil的细胞内共定位将体内治疗功效从仅给予Doxil或单独PNB的5-7%提高到90%,从而证明了基于PNB的细胞内药物释放的协同治疗效果。这种机制还将Doxil的非特异性毒性降低到可检测水平以下,并且治疗时间不到一分钟。因此,PNB联合收割机结合了高度敏感的诊断,克服了耐药性,并在用于术中治疗的单一快速治疗诊断程序中使非特异性毒性最小化。
The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-specific toxicity of the adjuvant treatment. We report a novel, theranostic in vivo technology that unites both the acoustic diagnostics and guided intracellular delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC-bearing mice were treated with gold nanoparticle conjugates, Doxil, and single near-infrared laser pulses of low energy. Tumor-specific clusters of gold nanoparticles (solid gold spheres) converted the optical pulses into localized PNBs. The acoustic signals of the PNB detected the tumor with high specificity and sensitivity. The mechanical impact of the PNB, co-localized with Doxil liposomes, selectively ejected the drug into the cytoplasm of cancer cells. Cancer cell-specific generation of PNBs and their intracellular co-localization with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic effect of the PNB-based intracellular drug release. This mechanism also reduced the non-specific toxicity of Doxil below a detectable level and the treatment time to less than one minute. Thus PNBs combine highly sensitive diagnosis, overcome drug resistance and minimize non-specific toxicity in a single rapid theranostic procedure for intra-operative treatment.
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