Biomimetic Human Serum Albumin Nanoparticle for Efficiently Targeting Therapy to Metastatic Breast Cancers.
Triple-negative breast cancers (TNBCs), devoid of hormone receptors and human epidermal growth-factor receptor-2/Neu expression, bring about poor prognosis and induce a high rate of systematic metastases. The ineffectiveness of current therapies on TNBCs could be attributed to the lack of efficient targeted therapy. Paclitaxel (PTX) is considered one of first-line chemotherapeutics for TNBC treatment but, due to its low aqueous solubility and nonspecific accumulation, results in poor antitumor efficacy. The present study is aimed at enhancing the chemotherapeutic potency of PTX by improving the stability and targeting efficiency of PTX-loaded nanoparticulate drug carriers. Here, PTX was incorporated in nontoxic and endogenous material, human serum albumin (HSA), via an innovative disulfide reduction method to construct HSA-based PTX nanoparticle (HSA-PTX NP) to not only realize redox-responsive drug release but also improve in vivo stability. Besides, W peptide was selected as a target ligand to be conjugated with HSA-PTX NP for endowing active targeting ability. The resulting Wpep-HSA-PTX NP possessed a spherical structure (118 nm), 9.87% drug-loading content, and 86.3% entrapment efficiency. An in vitro drug release test showed that PTX release from Wpep-HSA-PTX NP was of a redox-responsive manner. Furthermore, cellular uptake of Wpep-HSA-PTX NP was significantly enhanced, exhibiting the improved antiproliferation and antitube formation effects of PTX in vitro. In comparison with those commercial formulations and conventional HSA NP, Wpep-HSA-PTX NP exhibited better pharmacokinetic behaviors and tumor homing characteristics. The antitumor efficacy of Wpep-HSA-PTX NP was further confirmed by the strong pro-apoptotic effect and reduced tumor burden. In a word, this evidence highlighted the proof of concept for Wpep-HSA NP as a promising conqueror to the ineffectiveness of TNBC therapy.
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.|National Pharmaceutical Engineering and Research Center, China State Institute of Pharmaceutical Industry , Shanghai 201203, China.
Lisha
L
Liu
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.|Department of Neurosurgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine , Shanghai 201620, China.
Yunke
Y
Bi
National Pharmaceutical Engineering and Research Center, China State Institute of Pharmaceutical Industry , Shanghai 201203, China.
Muru
M
Zhou
National Pharmaceutical Engineering and Research Center, China State Institute of Pharmaceutical Industry , Shanghai 201203, China.
Xinli
X
Chen
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Xi
X
He
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Yujie
Y
Zhang
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Tao
T
Sun
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Chunhui
C
Ruan
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Qingjun
Q
Chen
National Pharmaceutical Engineering and Research Center, China State Institute of Pharmaceutical Industry , Shanghai 201203, China.
Hao
H
Wang
Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, Fudan University , 138 Yixueyuan Road, Shanghai 200032, China.
Chen
http://orcid.org/0000-0002-4833-9121
C
Jiang
D000818:Animals; D032701:Biomimetics; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006801:Humans; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009362:Neoplasm Metastasis; D017239:Paclitaxel; D000075462:Serum Albumin, Human
D004337:Drug Carriers; D017239:Paclitaxel; D000075462:Serum Albumin, Human
W peptide; disulfide reduction; drug delivery; human serum albumin; triple-negative breast cancer