Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response.
To overcome the drawbacks of high dose regimen and improve the outcomes of chemotherapy at a low dose, an immunotherapeutic nanoemulsion based combination of chemotherapeutic agent (paclitaxel) with immunomodulatory agent (vitamin E) was developed and evaluated for their antitumor effect against breast cancer.



A total of five nanoemulsions loaded with various content of vitamin E were prepared and characterized. The immunoregulatory effects of vitamin E along with the overall antitumor efficacy of vitamin E-rich nanoemulsion with a low dose of paclitaxel were investigated through in vitro and in vivo experiments.



Vitamin E-rich nanoemulsion exhibited relatively narrow size distribution, high entrapment efficiency and controlled in vitro release profile. In RAW264.7 cells, vitamin E-rich nanoemulsion significantly enhanced the secretion of Th1 cytokines and down-regulated the secretion of Th2 cytokine. In a co-culture system, vitamin E-rich nanoemulsion induced a high apoptosis rate in MDA-MB-231 cells as compared with vitamin E-low nanoemulsion. Furthermore, vitamin E-rich nanoemulsion exhibited superior in vivo antitumor efficacy in comparison with Taxol and vitamin E-low nanoemulsion at a paclitaxel dose of 4 mg/kg.



Vitamin E-rich nanoemulsion has great potential for the treatment of breast cancers with a low dose of paclitaxel via driving Th1 immune response.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.|Beijing Wehand-bio Pharmaceutical Co. Ltd., Beijing, 100260, People's Republic of China.
Jun
J
Ye
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
Wujun
W
Dong
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
Yanfang
Y
Yang
Beijing Wehand-bio Pharmaceutical Co. Ltd., Beijing, 100260, People's Republic of China.
Huazhen
H
Hao
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
Hengfeng
H
Liao
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
Bangyuan
B
Wang
Beijing Wehand-bio Pharmaceutical Co. Ltd., Beijing, 100260, People's Republic of China.
Xue
X
Han
Beijing Wehand-bio Pharmaceutical Co. Ltd., Beijing, 100260, People's Republic of China.
Yiqun
Y
Jin
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
Xuejun
X
Xia
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China. ylliu@imm.ac.cn.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China. ylliu@imm.ac.cn.
Yuling
Y
Liu
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004337:Drug Carriers; D004347:Drug Interactions; D004655:Emulsions; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016207:Cytokines; D004337:Drug Carriers; D004655:Emulsions; D014810:Vitamin E; D017239:Paclitaxel
Th1 immune response; immunochemotherapy; low-dose paclitaxel; nanoemulsion; vitamin E