Photochemical internalization enhanced macrophage delivered chemotherapy.

Photochemical internalization enhanced macrophage delivered chemotherapy.
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DOI:
10.1016/j.pdpdt.2017.12.002
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发表时间:
2018-03
影响因子:
3.3
通讯作者:
Hirschberg H
Hirschberg H
中科院分区:
医学3区
文献类型:
--
作者:
Shin D;Christie C;Ju D;Nair RK;Molina S;Berg K;Krasieva TB;Madsen SJ;Hirschberg H

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化疗药物的巨噬细胞(Ma)载体化对于癌症治疗具有优势,因为它可以主动靶向肿瘤部位并维持药物浓度升高,防止它们扩散到健康组织中。潜在的缺点是不能将足够数量的载药Ma递送到肿瘤中,因此限制了递送的活性药物的量。本研究考察了光化学内化(PCI)增强通过Ma转运释放药物的功效的能力。将由F98大鼠神经胶质瘤细胞或F98细胞与空的或多柔比星(DOX)负载的小鼠Ma(RAW264.7)亚群组合组成的肿瘤球状体用作体外肿瘤模型。用光敏剂AlPcS2a和670 nm的激光照射进行PCI。用DOX脉冲的RAW 264.7 Ma在孵育2小时内释放大部分掺入的DOX。PCI显著增加了作为纯药物或衍生自载DOX的Ma单层的DOX的毒性。即使在低至总初始杂交球状体细胞数的11%的DOX负载的Ma亚群中,也用PCI观察到杂交球状体的显著生长抑制。结果表明,RAW264.7Ma脉冲DOX能有效地掺入和释放DOX。PCI显著增加游离和MA释放的DOX抑制体外肿瘤球体生长的能力。与单独作用的光动力疗法或释放的DOX相比,PCI协同降低了F98+DOX负载的Ma杂合球状体的生长。
Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and laser irradiation at 670 nm. RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98+DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone.
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