title: Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells.
abstract: OBJECTIVE
  To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells.
  
  
  METHODS
  As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results.
  
  
  RESULTS
  To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced.
  
  
  CONCLUSIONS
  Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.
authors: Radiology Department, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors: Xian
authors: X
authors: Li
authors: Hao
authors: H
authors: Li
authors: Wei
authors: W
authors: Yi
authors: Jianyu
authors: J
authors: Chen
authors: Biling
authors: B
authors: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005492:Folic Acid; D018698:Glutamic Acid; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008823:Micelles; D010316:Particle Size; D011108:Polymers
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D008823:Micelles; D011108:Polymers; D018698:Glutamic Acid; D004317:Doxorubicin; D005492:Folic Acid
keywords: DOX; SPIONs; acid-triggered; folate-targeted effect; nanomicelle carrier
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