Poly(beta-amino ester) nanoparticles enable tumor-specific TRAIL secretion and a bystander effect to treat liver cancer.
Poly(beta-amino ester) nanoparticles enable tumor-specific TRAIL secretion and a bystander effect to treat liver cancer.
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DOI：
10.1016/j.omto.2021.04.004
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发表时间：
2021-06-25
期刊：
影响因子：
--
通讯作者：
Green JJ
中科院分区：
文献类型：
--
作者：
Vaughan HJ;Zamboni CG;Radant NP;Bhardwaj P;Revai Lechtich E;Hassan LF;Shah K;Green JJ
Despite initial promise, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based approaches to cancer treatment have yet to yield a clinically approved therapy, due to delivery challenges, a lack of potency, and drug resistance. To address these challenges, we have developed poly(beta-amino ester) (PBAE) nanoparticles (NPs), as well as an engineered cDNA sequence encoding a secretable TRAIL (sTRAIL) protein, to enable reprogramming of liver cancer cells to locally secrete TRAIL protein. We show that sTRAIL initiates apoptosis in transfected cells and has a bystander effect to non-transfected cells. To address TRAIL resistance, NP treatment is combined with histone deacetylase inhibitors, resulting in >80% TRAIL-mediated cell death in target cancer cells and significantly slowed xenograft tumor growth. This anti-cancer effect is specific to liver cancer cells, with up to 40-fold higher cell death in HepG2 cancer cells over human hepatocytes. By combining cancer-specific TRAIL NPs with small-molecule-sensitizing drugs, this strategy addresses multiple challenges associated with TRAIL therapy and offers a new potential approach for cancer treatment. Green and colleagues develop polymeric nanoparticles to program liver cancer cells to locally secrete tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). The authors show that the delivered sTRAIL initiates apoptosis in transfected liver cancer cells and has a bystander effect to non-transfected cancer cells, with potency enhanced by histone deacetylase inhibitors.
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影响因子：
4.8
作者：
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通讯作者：
Sun, Zhaoli
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17.1
作者：
Guerrero-Cazares, Hugo;Tzeng, Stephany Y.;Young, Noah P.;Abutaleb, Ameer O.;Quinones-Hinojosa, Alfredo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
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作者：
Bhise, Nupura S.;Gray, Ryan S.;Sunshine, Joel C.;Htet, Soe;Ewald, Andrew J.;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
50.3
作者：
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通讯作者：
Llovet, JM