Phospholipid-stabilized mesoporous carbon nanospheres as versatile carriers for systemic delivery of amphiphobic SNX-2112 (a Hsp90 inhibitor) with enhanced antitumor effect.
Systemic delivery of amphiphobic drugs (insoluble in both water and oil) represents a formidable challenge in drug delivery. This work aimed to engineer a functional mesoporous carbon material to efficiently load SNX-2112, an amphiphobic anticancer agent, and to evaluate its performance in tumor-targeting delivery. Hydrothermal reaction combined with high-temperature activation was used to fabricate glucose-based mesoporous carbon nanospheres (MCNs). SNX-2112-loaded MCNs stabilized by phospholipid (SN-PMCNs) were prepared by the absorption/solvent diffusion/high-pressure homogenization method. The obtained SN-PMCNs were 180nm around in particle size, showing a high drug load (42.7%) and acceptable physical stability. SN-PMCNs demonstrated an enhanced in vitro antitumor effect and increased uptake into cancer cells in comparison with the formulation of SNX-2112 solution (SN-Sol). The in vivo antitumor effect and biodistribution in 4T1 xenograft tumor mice, a breast cancer model, were also significantly improved through SN-PMCNs. It was shown that specific clathrin-dependent and nonspecific caveolae-dependent endocytosis were involved in the cellular trafficking of SN-PMCNs. Glucose transporter-mediated transport, prolonged body residence time and improved biodistribution via EPR effect were the main mechanisms of enhanced antitumor effect. SN-PMCNs have presented excellent tumor targeting properties and should be a promising carrier to address the systemic delivery of SNX-2112.
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Xingwang
X
Zhang
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Tianpeng
T
Zhang
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Yanghuan
Y
Ye
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Huaqing
H
Chen
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Hua
H
Sun
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Xiaotong
X
Zhou
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China.
Zhiguo
Z
Ma
Division of Pharmaceutics, College of Pharmacy, Jinan University, PR China. Electronic address: bj.wu@hotmail.com.
Baojian
B
Wu
D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002244:Carbon / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004705:Endocytosis; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056945:Hep G2 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates; D050997:Nanomedicine; D010743:Phospholipids / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D051246:Glucose Transport Proteins, Facilitative; D018841:HSP90 Heat-Shock Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D058726:Nanoconjugates; D010743:Phospholipids; C534922:SNX 2112; D002244:Carbon
Amphiphobic; Antitumor effect; Breast cancer; Mesoporous carbon; SNX-2112