Spatiotemporally light controlled "drug-free" macromolecules via upconversion-nanoparticle for precise tumor therapy
Spatiotemporally light controlled "drug-free" macromolecules via upconversion-nanoparticle for precise tumor therapy
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通过上转换纳米颗粒实现时空光控“无药”大分子，实现精准肿瘤治疗
DOI：
10.1016/j.nantod.2021.101360
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发表时间：
2022-02-01
期刊：
影响因子：
17.4
通讯作者：
Du, Yongzhong
中科院分区：
文献类型：
--
作者：
Wang, Jun;Qi, Jing;Du, Yongzhong
无药物的大分子治疗剂通过聚集非内化的细胞表面受体来诱导细胞凋亡，这在肿瘤治疗中已经显示出巨大的前景，特别是当与低分子量药物相比时在非特异性毒性方面。然而，大多数报道的无药物大分子治疗剂涉及“两步”给药方式，并且体内研究很少，可能给体内应用带来困难。本文采用近红外上转换控制交联法，在生物体内原位合成了一种不含药物的大分子治疗剂。以CD 20受体阳性的B细胞淋巴瘤为模型疾病，首先将带有肉桂酸酯侧基的聚甲基丙烯酸2-羟乙酯（CA）引入到上转换纳米颗粒（UCNP）表面，然后将其与抗CD 20适体功能化，得到Apt-pHEMA（CA）@UCNP。局部或全身给予Apt-pHEMA（CA）@UCNP+局部应用980-nm NIR激光后，肿瘤的生长被显著抑制，没有可检测到的毒性。探索Apt-pHEMA（CA）@UCNP与980-nm NIR激光联合的上级抗肿瘤效率，我们发现Apt-pHEMA（CA）@UCNP通过CD 20受体与抗CD 20适配体之间的相互作用结合到肿瘤细胞表面，而不引起细胞活力的任何降低。980 nm激光局部照射后，UCNP将近红外光转化为紫外光，导致CA基团交联，CD 20受体聚集，细胞凋亡。我们相信这种近红外上转换控制的原位合成的无药物大分子治疗剂扩展了大分子药物的库，并为肿瘤治疗开辟了新的途径。(c)2021爱思唯尔出版
Drug-free macromolecular therapeutics induce cell apoptosis by clustering non-internalizing cell-surface receptors, which has demonstrated great promise in tumor therapy, particularly in terms of non-specific toxicities when compared with low-molecular-weight drugs. However, most reported drug-free macro molecular therapeutics involve a 'two-step' administration manner and the in vivo study is scarce, likely imposing difficulties on in vivo application. Here, we in-situ synthesized a drug-free macromolecular therapeutic in living system by near-infrared up-conversion controlled cross-linking. Taking CD20 receptor positive B-cell lymphoma as the model disease, poly(2-hydroxyethyl methacrylate) with pendants of cinnamate groups (CA) were first introduced onto the surface of up-conversion nanoparticles (UCNP), which were then functionalized with anti-CD20 aptamer to give Apt-pHEMA(CA)@UCNP. After a local or systemic administration of Apt-pHEMA(CA)@UCNP plus the local application of 980-nm NIR laser, the growth of tumor was significantly suppressed with no detectable toxicities. Exploring the superior anti-tumor efficiency of Apt-pHEMA(CA)@UCNP combined with 980-nm NIR laser, we found that Apt-pHEMA(CA)@UCNP bound onto the surface of tumor cell by the interaction between CD20 receptors and anti-CD20 aptamers, without causing any reduction on cell viability. While after the local application of 980-nm laser, UCNP harvested the NIR light and converted it into UV light, which resulted in the cross-linking of CA groups, thus the clustering of CD20 receptors and cell apoptosis. We believe this NIR up-conversion controlled, in-situ synthesized drug-free macromolecular therapeutic expands the repertoire of macromolecular drugs and opens a new avenue for tumor therapy.(c) 2021 Published by Elsevier Ltd.