Wenchen Zhao - Profile on Academia.edu (original) (raw)
Related Authors
The Tamilnadu Dr. Mgr Medical University
Uploads
Papers by Wenchen Zhao
Bioconjugate Chemistry, 2013
S-trans, trans-farnesylthiosalicylic acid (FTS) is a synthetic small molecule that acts as a pote... more S-trans, trans-farnesylthiosalicylic acid (FTS) is a synthetic small molecule that acts as a potent and especially nontoxic Ras antagonist. It inhibits both oncogenically activated Ras and growth factor receptor-mediated Ras activation, resulting in the inhibition of Ras-dependent tumor growth. In this work, a FTS conjugate with polyethylene glycol (PEG) through a labile ester linkage, PEG 5K-FTS 2 (L), was developed. PEG 5K-FTS 2 conjugate readily forms micelles in aqueous solutions with a critical micelle concentration of 0.68 μM and hydrophobic drugs such as paclitaxel (PTX) could be effectively loaded into these particles. Both drug-free and PTX-loaded micelles were spherical in shape with a uniform size of 20 ~ 30 nm. The release of PTX from PTX-loaded PEG 5K-FTS 2 micelles was significantly slower than that from Taxol formulation. In vitro cytotoxicity studies with several tumor cell lines showed that PEG 5K-FTS 2 (L) was comparable to FTS in antitumor activity. Western immunoblotting showed that total Ras levels were downregulated in several cancer cell lines treated with FTS or PEG 5K-FTS 2 (L). The micellar formulation of PTX exhibited more in vitro cytotoxic activity against several tumor cell lines compared with free PTX, suggesting a possible synergistic effect between the carrier and the codelivered drug. The anti-tumor activity of the PTX loaded PEG 5K-FTS 2 (L) micelles in a syngeneic murine breast cancer model was found to be significantly higher than that of Taxol, which may be attributed to their preferential tumor accumulation and a possible synergistic effect between PEG 5K-FTS 2 carrier and loaded PTX.
Nature communications, Nov 7, 2016
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represen... more Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast...
Bioconjugate Chemistry, 2013
S-trans, trans-farnesylthiosalicylic acid (FTS) is a synthetic small molecule that acts as a pote... more S-trans, trans-farnesylthiosalicylic acid (FTS) is a synthetic small molecule that acts as a potent and especially nontoxic Ras antagonist. It inhibits both oncogenically activated Ras and growth factor receptor-mediated Ras activation, resulting in the inhibition of Ras-dependent tumor growth. In this work, a FTS conjugate with polyethylene glycol (PEG) through a labile ester linkage, PEG 5K-FTS 2 (L), was developed. PEG 5K-FTS 2 conjugate readily forms micelles in aqueous solutions with a critical micelle concentration of 0.68 μM and hydrophobic drugs such as paclitaxel (PTX) could be effectively loaded into these particles. Both drug-free and PTX-loaded micelles were spherical in shape with a uniform size of 20 ~ 30 nm. The release of PTX from PTX-loaded PEG 5K-FTS 2 micelles was significantly slower than that from Taxol formulation. In vitro cytotoxicity studies with several tumor cell lines showed that PEG 5K-FTS 2 (L) was comparable to FTS in antitumor activity. Western immunoblotting showed that total Ras levels were downregulated in several cancer cell lines treated with FTS or PEG 5K-FTS 2 (L). The micellar formulation of PTX exhibited more in vitro cytotoxic activity against several tumor cell lines compared with free PTX, suggesting a possible synergistic effect between the carrier and the codelivered drug. The anti-tumor activity of the PTX loaded PEG 5K-FTS 2 (L) micelles in a syngeneic murine breast cancer model was found to be significantly higher than that of Taxol, which may be attributed to their preferential tumor accumulation and a possible synergistic effect between PEG 5K-FTS 2 carrier and loaded PTX.
Nature communications, Nov 7, 2016
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represen... more Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast...