Versatile Prodrug Nanoparticles for Acid‐Triggered Precise Imaging and Organelle‐Specific Combination Cancer Therapy |
| |
| Authors: | Bing Feng Fangyuan Zhou Zhiai Xu Tingting Wang Dangge Wang Jianping Liu Yuanlei Fu Qi Yin Zhiwen Zhang Haijun Yu Yaping Li |
| |
| Affiliation: | 1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China;2. University of Chinese Academy of Sciences, Beijing, China;3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China;4. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China |
| |
| Abstract: | Integration of chemotherapy with photodynamic therapy (PDT) has been emerging as a novel strategy for treatment of triple negative breast cancer (TNBC). However, the clinical translation of this approach is hindered by the unwanted dark toxicity due to the “always‐on” model and low tumor specificity of currently approved photosensitizer (PS). Here, the design of a multifunctional prodrug nanoparticle (NP) is described for precise imaging and organelle‐specific combination cancer therapy. The prodrug NP is composed of a newly synthesized oxaliplatin prodrug, hexadecyl‐oxaliplatin‐trimethyleneamine (HOT), an acid‐activatable PS, derivative of Chlorin e6 (AC), and functionalized with a targeting ligand iRGD for tumor homing and penetration. HOT displays much higher antitumor efficiency than oxaliplatin by simultaneously inducing mitochondria depolarizing and DNA cross‐linking. AC is specifically activated in the orthotopic or metastatic TNBC tumor for fluorescence imaging and PDT, while it remains inert in blood circulation to minimize the dark toxicity. Under the guide of acid‐activatable fluorescence imaging, PDT and chemotherapy can be synergistically performed for highly efficient regression of TNBC. Taken together, this versatile prodrug nanoplatform could achieve tumor‐specific imaging and organelle‐specific combination therapy, which can provide an alternative option for cancer theranostic. |
| |
| Keywords: | chemotherapy organelle targeting oxaliplatin prodrug nanoparticles photodynamic therapy triple negative breast cancer |
|
|
